Structure–property relations of a unique and systematic dataset of 19 isostructural multicomponent apremilast forms

The structure–property relations are examined for apremilast cocrystals and solvates in this work. A unique and large dataset of multicomponent crystal forms is presented including 7 cocrystals and 12 solvates. In total, 15 of the presented multicomponent forms and their crystal structures are published here for the first time. This dataset is unique owing to the extreme crystal packing similarity of all 19 crystal forms. This fact makes the evaluation of structure–property relations significantly easier and more precise since the differences in the crystal lattice arrangement are close to negligible. Properties of the guest molecules used here can be directly correlated with the macroscopic properties of the corresponding multicomponent forms. Interestingly, a considerable correlation was found between the intrinsic dissolution rate of the multicomponent forms and their solubility, as well as the solubility of their guest molecules in the dissolution medium. The latter is of particular interest as it can aid in the design of multicomponent forms with tuned properties.

1. Introduction

In recent years, the pharmaceutical industry has been challenged with the task of increasing the solubility of poorly water-soluble drug products (Good & Rodríguez-Hornedo, 2009; Blagden et al., 2007; Chen et al., 2011). The biggest problem for oral drug administration – the most common method of treatment – is low bioavailability (Gavhane & Yadav, 2012; Pinnamaneni et al., 2002), which is a consequence of poor aqueous solubility (Lipinski, 2000). This issue is expected to be increasingly relevant in the coming years. In the current market, approximately 40% (Lipinski, 2002) of active pharmaceutical ingredients (APIs) have poor solubility and this number is expected to increase to 70–90% in the future (Thayer, 2010). Ongoing advances motivate academic and industrial researchers in the field of crystal engineering to search for modern multicomponent solid-state forms, i.e. salts, solvates and cocrystals. The formation of a new multicomponent form can significantly increase not only the solubility and thus the bioavailability, but also improve other important properties such as thermal stability, hygroscopicity, powder flowability, and physical as well as chemical stability (Qiao et al., 2011; Jia et al., 2015; Stanton & Bak, 2008). These properties are crucial in the process of drug development. However, designing new multicomponent forms with desired properties remains a difficult task. It requires skilled researchers and significant experimental and cost efforts, since a comprehensive theory describing the formation of such solids is yet to be developed. Further, the links between solid-state structures and macroscopic properties, such as solubility or thermal stability, are generally not well explored or understood. Thus, contributions from experimental research as well as mathematical modelling are essential to deepeen our understanding of the formation of new multicomponent forms and the relation between their crystal structure and macroscopic properties. Each contribution provides knowledge that helps to minimize experimental efforts for researchers and reduce industrial expense to make medicines more affordable.

The connection between the multicomponent crystal form and its properties has mostly been explored within salts (de Moraes et al., 2017; Arlin et al., 2011; Collier et al., 2006; Black et al., 2007). However, many proposed structure–property relations are valid only for small systems and cannot necessarily be applied to broader systems or different compounds. For example, the lack of versatility can be illustrated by contradicting observations, i.e. adding polar groups to API species can result in both increased as well as decreased aqueous solubility (Agharkar et al., 1976; Parshad et al., 2004). This problem is exacerbated by the lack of larger, systematically explored datasets that could provide both structural information of crystal forms as well as evaluation of reliable physicochemical data of specific forms, which is crucial for a clearer understanding of the structure–property relation. However, previous studies with larger sample sizes did not contain structural data (Streng et al., 1984). Recent studies report both the crystal structures and the properties of the prepared salts. Unfortunately, most of them contain a relatively small number of samples (Sanphui et al., 2014; Mannava et al., 2020; Gunnam & Nangia, 2019; Banik et al., 2016; Martin et al., 2013; Thakuria & Nangia, 2013; Goud et al., 2013). Several studies with systematic large datasets are now available (20–50 salts) that bring new insight into this topic (de Moraes et al., 2017; Arlin et al., 2011; Collier et al., 2006; Black et al., 2007). These systematic studies currently available for salts are not yet available for cocrystals and solvates, despite these multicomponent forms being of interest. The published literature provides a limited number of new cocrystals and solvates, which is insufficient to obtain reliable structure–property relations (Cadden et al., 2019). Ten cocrystals of AMG 517 were reported, accompanied with an evaluation of the physicochemical properties in order to correlate properties of various cocrystals (Stanton & Bak, 2008). Despite not obtaining structural data for most of the cocrystals, an interesting correlation of increasing cocrystal melting points with increasing guest molecule melting points was observed (Stepanovs et al., 2015; Stanton & Bak, 2008; Aakeröy et al., 2006). A different, more detailed analysis of cocrystal melting points across a broader system of compounds was performed by Schultheiss & Newman (2009), showing that 51% of the examined cocrystals had a melting point between those of the API and the guest molecule, 39% had a melting point lower than both the API and the guest molecule, 6% were higher than both, and 4% were same as the API or the guest molecule.

Most of the scientific literature about cocrystals and solvates currently available does not focus on structure–property relations or does not contain sufficiently large datasets to draw conclusions. Furthermore, introducing different guest molecules into a multicomponent crystal can completely change the crystal lattice. Even the properties of polymorphs, containing only a single compound with a different crystal arrangement, change significantly (Zvoníček et al., 2018; Aguiar et al., 1967; Aguiar & Zelmer, 1969; Bauer et al., 2001). Therefore, by comparing multicomponent solid forms, changes in the crystal lattice are shown to impact the physicochemical properties to the same extent as the chemical nature of the guest molecule (de Moraes et al., 2017).

2. Experimental

2.1. Intrinsic dissolution rate

The intrinsic dissolution rate (IDR) was determined using a Sirius inForm (Pion Inc. USA) device. IDR discs with a 6 mm diameter were prepared by compression of 40–60 mg of the tested material. The material was compressed at a constant load of 100 kg, relaxed for 1 min and compressed again at a constant load of 100 kg for a further 1 min. IDR measurements were performed in 40 ml phosphate buffer solution at pH 6.8 with the addition of 0.2% of sodium do­decyl sulfate (SDS) at a stirring speed of 100 rpm. UV spectra were recorded every 8 s using a 20 mm optical path length. Absorbance between wavelengths of 300 and 400 nm was used to evaluate the amount of API released at each time point. The IDR was calculated using a linear fit (R² > 0.90) of the experimental data over the minimum time frame of 2 min. Three measurement averages were used for the final IDR evaluation.

2.2. Differential scanning calorimetry

Samples for differential scanning calorimetry (DSC) measurements were weighed in an aluminium pan (∼10 mg). The pan was covered, and the measurement was carried out under a nitro­gen gas flow of 50 ml min⁻¹. All measurements were performed on the TA Instruments Discovery DSC. The investigated temperatures ranged from 0 to 300°C at a heating rate of 10°C min⁻¹ (amplitude = 0.8°C; period = 60 s).

2.3. Equilibrium solubility

Multicomponent form samples were analyzed using the Waters Acquity UPLC system equipped with a PDA detector (measured at 230 nm wavelength) and an Acquity BEH Phenyl column (100 × 2.1 mm; 1.7 µm). The temperature of the column was 45°C. The following gradient of 0.1% (v/v) phospho­ric acid/aceto­nitrile at a flow rate of 0.35 ml min⁻¹ was used: steady state (0–0.5 min) followed by linear gradient from 70/30 to 20/80 (0.5–1.5 min) followed by steady state (1.5–2.5 min) and a linear gradient back to the starting conditions (2.5–3 min) followed by steady state for 2 min of re-equilibration. The injection volume was 1 µl. The data were processed using the EMPOWER software.

2.4. X-ray powder diffraction

The diffraction patterns were collected with the powder diffractometer device X'PERT PRO MPD PANalytical, a Cu Kα X-ray beam (λ = 1.542 Å), 2–40° 2θ measured range, 45 kV excitation voltage, 40 mA anodic current, 0.01° 2θ step size and a 0.05 s step duration. The measurement was performed on a flat sample with an area:thickness ratio equal to 10:0.5 mm. The 0.02 rad Soller slits, 10 mm mask and 1/4° fixed anti-scattering slits were used to correct the primary beam. The irradiated area of the sample was 10 mm; programmable divergent slits were used. The 0.02 rad Soller slits and 5.0 mm anti-scattering slits were used to correct the secondary beam. The HighScore Plus software (Degen et al., 2014) was used to process the diffraction patterns.

2.5. Raman spectroscopy

Samples for Raman spectroscopy were measured in HPLC glass vials in an FT-Raman RFS100/S spectrometer device with a germanium detector (Bruker Optics, Germany). The wavelength of the Nd:YAG laser was 1064 nm. The range measured was 4000 to 200 cm⁻¹, with a spectral resolution of 4.0 cm⁻¹. Data were obtained either at 64 or 128 accumulations of the measured spectra. The software OMNIC and OPUS were used to process the Raman spectra.

2.6. Single-crystal X-ray diffraction

X-ray analyses of the apremilast multicomponent forms were performed either at 95 K using a SuperNova diffractometer with a micro-focus sealed tube, mirror-collimated Cu Kα radiation (λ = 1.54184 Å) and CCD detector Atlas S2; or at 120 K on an Xcalibur, Gemini ultra diffractometer using Cu Kα radiation (λ = 1.54178 Å) from a fine-focus sealed X-ray tube with a graphite monochromator and CCD detector Atlas S2.

The data reduction and absorption correction were carried out with CrysAlisPro (Rigaku Oxford Diffraction, 2019). The structure was solved by charge flipping methods using the Superflip software (Palatinus & Chapuis, 2007) and refined by full matrix least squares on the F-squared value using the Crystals software (Betteridge et al., 2003). The MCE software (Rohlíček & Hušák, 2007) was used for visualization of residual electron density maps. According to common practice, hydrogen atoms attached to carbon atoms were assigned geometrically with U_iso (H) in the range 1.2–1.5 U_eq of the parent atom (C).

3. Results and discussion

This study reports 15 new cocrystals and solvates of the pharmaceutical molecule apremilast, which is used for the treatment of psoriasis and psoriatic arthritis (Zerilli & Ocheretyaner, 2015; Afra et al., 2019). The structures of all new forms were determined by single-crystal X-ray diffraction (SCXRD) and their physicochemical properties were evaluated. The properties of five known, similar multicomponent apremilast forms (Wu et al., 2017; Jirát et al., 2019, 2020) were included to provide a slightly larger dataset to draw more precise conclusions. Please note, the pharmaceutical relevance of the guest molecule was not considered in order to enlarge the dataset. New cocrystals of apremilast crystallized with 2,4-di­hydroxy­benzoic acid (24HB_C), 2,5-di­hydroxy­benzoic acid (25HB_C), 4-hy­droxy­benzoic acid (4HB_C), nicotinamide (NCA_C) and salicylic acid (SCA_C); and solvates with anisole (ANI_S), bromo­benzene (BRB_S), chloro­benzene (CLB_S), hexa­fluoro­benzene (HFBs), iodo­benzene (IOB_S), mesitylene (MST_S), m-xylene (MXY_S), p-xylene (PXY_S) and α,α,α-tri­fluoro­toluene (TFT_S). Other multicomponent forms from the literature (Wu et al., 2017; Jirát et al., 2019, 2020) and used in this study crystallized with phthalic acid (PHT_C), benzoic acid (BAC_C), toluene (TOL_S), o-xylene (OXY_S) and fluoro­benzene (FLB_S). Their respective chemical structures together with that of apremilast are presented in Fig. 1.

Figure 1 (a) Molecule of apremilast, (b) guest molecules, (c) crystal structure of cocrystals and solvates (o-xylene solvate is shown as an example).

Since the structural analysis of similar apremilast solid forms is already well discussed in the scientific literature (Jirát et al., 2020; Dudek et al., 2019), and our new crystal structures are isostructural, only key aspects of these systems are mentioned below (crystallographic details are provided in the supporting information). All new solid forms crystallized in the tetragonal system with the P4₁2₁2 space group and cell parameters (a ≃ 13 Å, c ≃ 29 Å). The ratio between the API and the guest molecule is 2:1. The observed pattern, which is similar for all investigated forms, is the π–π stacking interaction of the guest molecule benzene ring with the phthalimide group of the apremilast molecule. It is important to emphasize that all 19 cocrystals and solvates used throughout this study are isostructural (see Fig. 2).

Figure 2 (a) Dendrogram showing the packing similarity between all forms studied here, produced using CrystalCMP. (b) 2,4-Di­hydroxy­benzoic acid cocrystal, (c) bromo­benzene solvate and (d) mesitylene solvate, all showing similar crystal packing displayed along the c axis. Hydrogen atoms have been omitted for clarity.

All prepared forms are compared in Fig. 2(a) using the CrystalCMP software (Rohlíček et al., 2016) and the results show high packing similarity between all 19 forms used (a detailed description of CrystalCMP is given in the supporting information). The two forms with the biggest differences in crystal packing are shown in Figs. 2(b) and 2(d) and one in between [Fig. 2(c)] for reference. It is immediately evident that, despite choosing the most different forms, they still exhibit very similar crystal packing. Such a level of crystal packing similarity is very rare for multicomponent forms of APIs. It is interesting from a crystallography point of view, and it presents a close-to-ideal system to study structure–property relations.

The isostructurality of these samples ensures that the impact of the crystal lattice will be minimal or negligible. This allows for a more direct correlation between the properties of the guest molecule and the properties of the respective multicomponent form within a large and isostructural dataset. The physicochemical properties evaluated were thermal stability (melting temperature, T_m), IDR and equilibrium solubility (EqSol), which are commonly determined for new solid forms and are crucial for pharmaceutical development.

First, we evaluated the melting temperatures of the multicomponent solids, which range from 139°C (tri­fluoro­toluene solvate) to 190°C (salicylic acid cocrystal); for more details, refer to the supporting information. DSC curves obtained confirmed phase purity of the prepared multicomponent forms and were further used to examine the correlation between melting points of the multicomponent solids and their guest molecules (Fig. 3).

Figure 3 Melting points of multicomponent forms and guest molecules. Cocrystals are marked with black circles and solvates with blue diamonds. A linear fit of the data gives an R^2 of 0.1366.

Data presented in Fig. 3 indicate there is no relation between the melting points of the guest molecules and the multicomponent forms. The melting points of the solvates and cocrystals were further compared in their respective groups (solvates with solvents and cocrystals with coformers), but still no relation was observed. The melting points were further studied revealing that 1 in 19 (∼5%) multicomponent forms has a lower melting point than both apremilast and the guest molecule, 7 in 19 (∼37%) have a melting point between those of apremilast and the guest molecule, and 11 in 19 (∼59%) have a higher melting point than apremilast and the guest molecule. These findings depart from the majority of the experimental data published in the literature (Schultheiss & Newman, 2009; Stepanovs et al., 2015; Stanton & Bak, 2008; Aakeröy et al., 2006). However, there are studies that report similar results to ours (Stanton et al., 2009). This suggests that there will not be a simple and universal correlation between melting points of multicomponent forms and their guest molecules. It is possible to discover correlations in smaller systems, while considering the chemical nature of the guest molecules. However, for larger datasets and various compounds this might not be the case. In fact, as concluded from Fig. 3, it was not possible to find any relation despite the isostructurality of the prepared apremilast multicomponent forms. The interactions of guest molecules with apremilast molecules are different for each guest molecule despite occupying the same position in the crystal lattice; this is due to their changing chemical nature. The different intermolecular interactions can cause differences in thermal behaviour and make the idea of simple correlations invalid across broad systems. On the other hand, a deeper understanding of the intermolecular interactions, with improving crystal lattice calculations and better testing datasets in recent years might lead to successful predictions and correlations of melting points in the future.

The IDR was measured and evaluated for 17 samples (the IDR measurement was unsuccessful for iodo­benzene solvent and the salicylic acid cocrystal). The IDR ranges from 5 to 159 µg min⁻¹ cm⁻², the lowest IDR was observed for o-xylene solvate and the highest for 2,5-di­hydroxy­benzoic acid cocrystal. The up to tenfold increase in IDR for some of the new forms is very significant compared with the solid-state form used in the original drug product, which has an IDR of ∼14 µg min⁻¹ cm⁻² (for more details refer to the supporting information). The IDR values were compared with the melting temperatures of the samples.

Data presented in Fig. 4 indicate that there is no relation between IDR and the melting points of these isostructural apremilast forms. Stanton and Bak examined similar correlations of IDR and melting temperature for cocrystals and discovered only a very weak correlation (Stanton & Bak, 2008) or no correlation at all (Stanton et al., 2009), which is mostly in agreement with the data presented here. These outcomes suggest that it is not possible to estimate the dissolution rate of multicomponent forms based on their melting temperature. The IDRs of the solvates are significantly lower compared with those of the cocrystals. This difference might be partially explained by the differences in polarity of the guest molecules. The polarity of the guest molecules presented ranges widely from non-polar or slightly polar, such as mesitylene or xylenes, to very polar molecules, such as benzoic or salicylic acid. More polar molecules might display higher IDRs due to their ability to compete with hydrogen bonds of water molecules, thus being more readily soluble. This phenomenon affects the IDR of a multicomponent form as the guest molecule is the integral part.

Figure 4 Correlation of melting temperatures and IDRs of the multicomponent forms. Cocrystals are marked with black circles and solvates with blue diamonds. A linear fit of the data gives an R^2 of 0.0881.

It is important to note that the solid phases of the measured samples were evaluated before and after the IDR measurement and a solid-state transformation did not occur in any of these cases. This shows high phase stability of the apremilast multicomponent forms in the dissolution media for the time period of the measurement (∼1 h).

Since the IDR and melting points are not correlated, it is convenient to examine whether the IDR relates to the EqSol of the guest molecule in the same dissolution medium or the EqSol of the new multicomponent forms.

In this case, it is possible to observe a correlation between the IDR of the multicomponent form with the EqSol of both the multicomponent form and the guest molecule. The correlation between the IDR of the multicomponent form and EqSol of its guest molecule might be of strong interest. This would allow us to estimate the IDR of the multicomponent form in advance which would be beneficial in the design. Such an estimation of the solid-state form IDR prior to its formation could save in costs and experimental efforts during drug development. Especially as IDR is one of the crucial parameters that impacts bioavailability.

Since this is a real system, deviations from the correlations are observed for some samples despite the high similarity of the prepared multicomponent forms. Fluoro­benzene and tri­fluoro­toluene solvates deviate from the correlation and are marked with black circles in Fig. 5(a). This might be caused by the high electronegativity of the fluorine atoms, which can impact intermolecular interactions within the crystal lattice of individual multicomponent forms. These interactions play a major role and might cause the deviations from the observed relations. It is necessary to study these interactions further as they may account for the behaviour of the samples that do not fit the trend.

Figure 5 (a) and (b) Correlation of IDR and EqSol of multicomponent forms. (c) and (d) Correlation of IDR of the multicomponent forms and EqSol of the respective guest molecules. Note, nicotinamide is not included here since its EqSol is several orders of magnitude higher compared with the EqSol values of other guest molecules. Cocrystals are marked with black circles, solvates with blue diamonds and pure apremilast with red squares. (a) and (c) Linear plots; (b) and (d) log–log plots. A logarithmic fit of the data in (a) gives an R^2 of 0.56 with outliers and an R^2 of 0.94 without outliers marked with black circles. A linear fit of the data in (b) gives an R^2 of 0.76.

4. Conclusions

We report 15 new, isostructural multicomponent solids of apremilast, both cocrystals and solvates, with solved crystal structures from SCXRD. With an additional 5 similar and already published forms, we created a large and unique dataset of 19 isostructural solid forms. This dataset provides the possibility to systematically explore structure–property relations within multicomponent isostructural solids. The physicochemical properties evaluated were melting point, intrinsic dissolution rate and thermodynamic solubility, which are commonly characterized for new solids and are important for pharmaceutical drug development. We observed no relation between the melting points of the multicomponent forms and their guest molecules. In addition, no correlation was found between the melting points and the intrinsic dissolution rate of the multicomponent forms. However, a considerable correlation was found between the intrinsic dissolution rate of the multicomponent forms and their solubility as well as the solubility of their guest molecules. The correlation with the solubility of guest molecules is particularly interesting as it could help with the design of multicomponent forms with desirable properties. Overall, it is clear that discovering universal and simple correlations across a broad system of compounds and structures is a difficult task if not an impossible one. Even in this almost ideal and so far unique system, there are a few deviations from the observed correlations. The contribution of the calculation approach will shed new light on the specific differences in the intermolecular interactions, and obtaining more well defined datasets would be beneficial for future progress in the crystal engineering field. For now, as far as we know, this is the most reliable experimental dataset available and correlations drawn for non-ionized multicomponent solid forms.

5. Related literature

The following references are cited in the supporting information: Dudek et al. (2018); Wang et al. (2018); Chiou et al. (1977); Valvanix et al. (1981); Isao et al. (1982); Freire et al. (2005); Van Arnum (2000); Nian (2016); Yalkowsky & Dannenfleser (1992); Yalkowsky & He (1992); Yalkowsky et al. (2010).

Supporting information

Computing details

Data collection: SuperNova, (Oxford Diffraction, 2010) for Apremilast24dihydroxybenzoicacid, apremilast25dihydrbenzoic, Apremilast_4_hydroxybenzoic_acid, apremilastanisol, apremilast_brombenzen, Apremilast_chlorbenzen, apremilastiodobenzene, apremilastmesitilene, apremilastmetaxylene, apremilastnicotinamide, apremilastniacin, Apremilast_paraxylene, apremilastsalycilic, Apremilasttrifluorotoluene; CrysAlis PRO 1.171.40.67a (Rigaku OD, 2019) for ApreHexa. Cell refinement: CrysAlis PRO (Rigaku Oxford Diffraction, 2017) for Apremilast24dihydroxybenzoicacid, Apremilast_4_hydroxybenzoic_acid, apremilast_brombenzen, Apremilast_paraxylene; CrysAlis PRO, (Agilent, 2011) for apremilast25dihydrbenzoic, apremilastanisol, Apremilast_chlorbenzen, apremilastiodobenzene, apremilastmesitilene, apremilastmetaxylene, apremilastnicotinamide, apremilastniacin, apremilastsalycilic, Apremilasttrifluorotoluene; CrysAlis PRO 1.171.40.67a (Rigaku OD, 2019) for ApreHexa. Data reduction: CrysAlis PRO (Rigaku Oxford Diffraction, 2017) for Apremilast24dihydroxybenzoicacid, Apremilast_4_hydroxybenzoic_acid, apremilast_brombenzen, Apremilast_paraxylene; CrysAlis PRO, (Agilent, 2011) for apremilast25dihydrbenzoic, apremilastanisol, Apremilast_chlorbenzen, apremilastiodobenzene, apremilastmesitilene, apremilastmetaxylene, apremilastnicotinamide, apremilastniacin, apremilastsalycilic, Apremilasttrifluorotoluene; CrysAlis PRO 1.171.40.67a (Rigaku OD, 2019) for ApreHexa. Program(s) used to solve structure: Superflip (Palatinus & Chapuis, 2007) for Apremilast24dihydroxybenzoicacid, apremilast25dihydrbenzoic, Apremilast_4_hydroxybenzoic_acid, Apremilast_chlorbenzen, apremilastmesitilene, apremilastmetaxylene, apremilastnicotinamide; SIR92 (Altomare et al., 1994) for apremilastanisol, apremilast_brombenzen, apremilastiodobenzene, apremilastniacin, Apremilast_paraxylene, apremilastsalycilic, Apremilasttrifluorotoluene. Program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003) for Apremilast24dihydroxybenzoicacid, apremilast25dihydrbenzoic, Apremilast_4_hydroxybenzoic_acid, apremilastanisol, apremilast_brombenzen, Apremilast_chlorbenzen, apremilastiodobenzene, apremilastmesitilene, apremilastmetaxylene, apremilastnicotinamide, apremilastniacin, Apremilast_paraxylene, apremilastsalycilic, Apremilasttrifluorotoluene. Molecular graphics: CAMERON (Watkin et al., 1996) for Apremilast24dihydroxybenzoicacid, apremilast25dihydrbenzoic, Apremilast_4_hydroxybenzoic_acid, apremilastanisol, apremilast_brombenzen, Apremilast_chlorbenzen, apremilastiodobenzene, apremilastmesitilene, apremilastmetaxylene, apremilastnicotinamide, apremilastniacin, Apremilast_paraxylene, apremilastsalycilic, Apremilasttrifluorotoluene. Software used to prepare material for publication: CRYSTALS (Betteridge et al., 2003) for Apremilast24dihydroxybenzoicacid, apremilast25dihydrbenzoic, Apremilast_4_hydroxybenzoic_acid, apremilastanisol, apremilast_brombenzen, Apremilast_chlorbenzen, apremilastiodobenzene, apremilastmesitilene, apremilastmetaxylene, apremilastnicotinamide, apremilastniacin, Apremilast_paraxylene, apremilastsalycilic, Apremilasttrifluorotoluene.

(Apremilast24dihydroxybenzoicacid)

Crystal data

C25.50H26N2O9S	Dx = 1.452 Mg m^−3
Mr = 536.56	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 56131 reflections
a = 12.9189 (1) Å	θ = 4–68°
c = 29.4056 (1) Å	µ = 1.69 mm^−1
V = 4907.74 (8) Å^3	T = 120 K
Z = 8	Prism, colorles
F(000) = 2248	0.37 × 0.17 × 0.15 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4409 reflections with I > 2.0σ(I)
Focussing mirrors monochromator	Rint = 0.033
ω scans	θmax = 67.9°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro (Rigaku Oxford Diffraction, 2017)	h = −15→15
Tmin = 0.66, Tmax = 0.77	k = −15→15
94480 measured reflections	l = −35→35
4464 independent reflections

Refinement

Refinement on F^2	H-atom parameters constrained
Least-squares matrix: full	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.07P)^2 + 5.73P] , where P = (max(Fo^2,0) + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.048	(Δ/σ)max = 0.006
wR(F^2) = 0.130	Δρmax = 0.64 e Å^−3
S = 1.00	Δρmin = −0.61 e Å^−3
4462 reflections	Extinction correction: Larson (1970), Equation 22
363 parameters	Extinction coefficient: 107 (19)
62 restraints	Absolute structure: Parsons, Flack & Wagner (2013), 1809 Friedel Pairs
Primary atom site location: other	Absolute structure parameter: 0.013 (3)
Hydrogen site location: difference Fourier map

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.40546 (6)	0.16440 (6)	0.46468 (3)	0.0289
O2	0.31274 (19)	0.21203 (19)	0.44718 (8)	0.0370
O3	0.4471 (2)	0.07730 (18)	0.44010 (8)	0.0386
C4	0.3821 (3)	0.1275 (3)	0.52101 (13)	0.0441
C5	0.5021 (2)	0.2600 (2)	0.47030 (10)	0.0269
C6	0.5468 (2)	0.2970 (2)	0.42509 (9)	0.0251
N7	0.4660 (2)	0.34496 (19)	0.39634 (8)	0.0250
C8	0.4006 (3)	0.4253 (2)	0.40933 (10)	0.0274
C9	0.3257 (3)	0.4402 (2)	0.37216 (10)	0.0274
C10	0.3478 (2)	0.3684 (2)	0.33859 (10)	0.0256
C11	0.4382 (2)	0.3066 (2)	0.35353 (10)	0.0247
O12	0.40790 (19)	0.47246 (17)	0.44530 (7)	0.0318
O13	0.48132 (18)	0.23543 (17)	0.33397 (7)	0.0294
C14	0.2444 (3)	0.5096 (3)	0.36805 (12)	0.0338
C15	0.1879 (3)	0.5043 (3)	0.32802 (13)	0.0369
C16	0.2100 (3)	0.4341 (3)	0.29397 (12)	0.0322
C17	0.2922 (2)	0.3638 (2)	0.29797 (10)	0.0263
N18	0.3217 (2)	0.2917 (2)	0.26546 (9)	0.0285
C19	0.2803 (3)	0.2741 (2)	0.22319 (10)	0.0293
C20	0.3406 (3)	0.2003 (3)	0.19450 (11)	0.0368
O21	0.20114 (18)	0.31641 (19)	0.20976 (8)	0.0362
C22	0.6391 (2)	0.3685 (2)	0.43213 (11)	0.0280
C23	0.6540 (3)	0.4246 (2)	0.47225 (11)	0.0289
C24	0.7397 (3)	0.4877 (3)	0.47793 (11)	0.0317
C25	0.8129 (3)	0.4958 (3)	0.44257 (13)	0.0344
C26	0.7984 (3)	0.4404 (3)	0.40301 (12)	0.0356
C27	0.7112 (3)	0.3767 (3)	0.39780 (11)	0.0333
O28	0.75982 (18)	0.5458 (2)	0.51598 (9)	0.0403
C29	0.6819 (3)	0.5451 (3)	0.55083 (13)	0.0422
C30	0.7110 (3)	0.6244 (4)	0.58608 (18)	0.0690
O31	0.89655 (19)	0.5588 (2)	0.45102 (10)	0.0448
C32	0.9668 (3)	0.5729 (4)	0.41403 (15)	0.0639
O33	0.4478 (12)	0.7014 (12)	0.3284 (6)	0.1736	0.5000
O34	0.3565 (11)	0.7443 (11)	0.2666 (5)	0.1721	0.5000
C35	0.3952 (11)	0.6748 (7)	0.2952 (6)	0.1556	0.5000
C36	0.4462 (5)	0.5840 (5)	0.27224 (7)	0.1166
C37	0.5276 (5)	0.5306 (6)	0.2923 (3)	0.1334
C38	0.5796 (5)	0.4505 (6)	0.2708 (2)	0.1165
O39	0.6562 (9)	0.4193 (10)	0.2966 (5)	0.1718	0.5000
O40	0.5628 (9)	0.5519 (10)	0.3320 (4)	0.1698	0.5000
H52	0.5574	0.2291	0.4883	0.0328*
H51	0.4720	0.3194	0.4860	0.0326*
H61	0.5706	0.2358	0.4090	0.0292*
H202	0.2993	0.1775	0.1687	0.0549*
H201	0.4036	0.2305	0.1830	0.0559*
H203	0.3600	0.1389	0.2113	0.0555*
H161	0.1683	0.4338	0.2674	0.0380*
H151	0.1297	0.5504	0.3246	0.0448*
H141	0.2304	0.5575	0.3916	0.0402*
H271	0.7020	0.3361	0.3702	0.0391*
H261	0.8470	0.4419	0.3794	0.0407*
H321	1.0215	0.6207	0.4233	0.0897*
H323	0.9990	0.5066	0.4067	0.0905*
H322	0.9309	0.5993	0.3879	0.0899*
H231	0.6055	0.4191	0.4963	0.0321*
H292	0.6789	0.4754	0.5644	0.0512*
H291	0.6130	0.5604	0.5384	0.0513*
H301	0.6549	0.6342	0.6074	0.0952*
H303	0.7747	0.6040	0.6016	0.0946*
H302	0.7216	0.6877	0.5695	0.0949*
H41	0.4455	0.0971	0.5330	0.0648*
H43	0.3627	0.1884	0.5389	0.0646*
H42	0.3259	0.0781	0.5206	0.0651*
H181	0.3724	0.2538	0.2731	0.0317*
H371	0.5463	0.5524	0.3222	0.1504*	0.5000
H381	0.6344	0.4159	0.2864	0.1383*	0.5000
H361	0.4079	0.6356	0.2890	0.1400*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0316 (4)	0.0278 (4)	0.0273 (3)	−0.0053 (3)	−0.0007 (3)	0.0030 (3)
O2	0.0323 (12)	0.0407 (13)	0.0381 (12)	−0.0017 (10)	−0.0072 (10)	−0.0004 (11)
O3	0.0432 (13)	0.0300 (12)	0.0427 (13)	−0.0035 (10)	−0.0018 (11)	−0.0033 (10)
C4	0.050 (2)	0.044 (2)	0.0381 (18)	−0.0080 (17)	0.0045 (16)	0.0155 (16)
C5	0.0318 (16)	0.0272 (15)	0.0217 (13)	−0.0040 (12)	−0.0006 (12)	0.0015 (12)
C6	0.0280 (15)	0.0254 (14)	0.0220 (13)	0.0006 (12)	0.0016 (12)	−0.0015 (11)
N7	0.0305 (13)	0.0238 (12)	0.0208 (11)	−0.0001 (10)	0.0049 (10)	−0.0025 (10)
C8	0.0321 (16)	0.0227 (15)	0.0275 (15)	0.0006 (13)	0.0077 (13)	−0.0008 (12)
C9	0.0310 (16)	0.0234 (14)	0.0276 (14)	−0.0034 (12)	0.0051 (13)	−0.0031 (12)
C10	0.0277 (15)	0.0219 (14)	0.0272 (14)	−0.0033 (12)	0.0065 (12)	0.0012 (11)
C11	0.0310 (16)	0.0224 (14)	0.0207 (13)	−0.0042 (12)	0.0054 (12)	−0.0016 (11)
O12	0.0421 (13)	0.0281 (11)	0.0252 (10)	0.0002 (10)	0.0043 (10)	−0.0063 (9)
O13	0.0335 (12)	0.0287 (11)	0.0259 (10)	0.0048 (9)	0.0025 (9)	−0.0042 (9)
C14	0.0365 (17)	0.0279 (16)	0.0369 (17)	0.0025 (14)	0.0045 (14)	−0.0078 (14)
C15	0.0338 (18)	0.0304 (17)	0.0467 (19)	0.0077 (14)	−0.0016 (15)	−0.0059 (15)
C16	0.0292 (16)	0.0295 (16)	0.0379 (18)	0.0009 (13)	−0.0004 (14)	−0.0042 (13)
C17	0.0276 (15)	0.0252 (15)	0.0260 (15)	−0.0022 (12)	0.0027 (12)	−0.0006 (12)
N18	0.0261 (13)	0.0298 (14)	0.0294 (13)	0.0044 (11)	−0.0008 (11)	−0.0043 (11)
C19	0.0310 (17)	0.0301 (16)	0.0268 (15)	−0.0040 (13)	0.0025 (13)	0.0004 (13)
C20	0.0393 (18)	0.0420 (19)	0.0289 (16)	0.0009 (16)	−0.0021 (14)	−0.0069 (14)
O21	0.0346 (12)	0.0401 (13)	0.0339 (12)	0.0043 (11)	−0.0050 (10)	−0.0006 (10)
C22	0.0298 (16)	0.0244 (15)	0.0298 (15)	0.0013 (13)	0.0035 (12)	0.0012 (12)
C23	0.0312 (16)	0.0251 (15)	0.0305 (15)	−0.0013 (12)	0.0087 (13)	−0.0029 (12)
C24	0.0271 (16)	0.0278 (16)	0.0401 (17)	0.0007 (12)	0.0029 (13)	−0.0030 (13)
C25	0.0277 (16)	0.0264 (16)	0.0493 (19)	−0.0012 (13)	0.0037 (14)	0.0090 (15)
C26	0.0338 (17)	0.0355 (18)	0.0376 (17)	0.0038 (14)	0.0107 (15)	0.0105 (14)
C27	0.0335 (17)	0.0357 (18)	0.0308 (16)	0.0045 (13)	0.0078 (14)	0.0039 (14)
O28	0.0306 (12)	0.0377 (13)	0.0525 (14)	−0.0045 (10)	0.0049 (11)	−0.0154 (11)
C29	0.0288 (17)	0.051 (2)	0.0470 (19)	0.0015 (15)	0.0022 (15)	−0.0220 (18)
C30	0.038 (2)	0.093 (4)	0.075 (3)	−0.002 (2)	0.000 (2)	−0.053 (3)
O31	0.0297 (12)	0.0453 (14)	0.0596 (16)	−0.0089 (11)	0.0061 (12)	0.0110 (13)
C32	0.032 (2)	0.105 (4)	0.054 (2)	−0.024 (2)	−0.0044 (18)	0.041 (3)
O33	0.145 (9)	0.175 (10)	0.201 (11)	0.010 (9)	−0.007 (9)	0.058 (9)
O34	0.157 (9)	0.179 (10)	0.180 (10)	0.062 (8)	0.031 (8)	0.056 (8)
C35	0.137 (8)	0.151 (8)	0.179 (9)	0.017 (7)	0.008 (7)	0.052 (7)
C36	0.097 (5)	0.111 (5)	0.142 (6)	−0.042 (4)	0.024 (4)	0.043 (4)
C37	0.108 (5)	0.155 (6)	0.137 (6)	−0.076 (4)	0.015 (4)	0.037 (5)
C38	0.072 (4)	0.140 (6)	0.137 (6)	−0.024 (4)	0.028 (4)	0.050 (5)
O39	0.106 (7)	0.198 (10)	0.212 (10)	0.003 (8)	0.016 (8)	0.044 (9)
O40	0.157 (8)	0.187 (9)	0.166 (9)	−0.079 (8)	0.005 (8)	0.032 (9)

Geometric parameters (Å, º)

S1—O2	1.442 (3)	C22—C23	1.397 (4)
S1—O3	1.441 (3)	C22—C27	1.378 (4)
S1—C4	1.750 (4)	C23—C24	1.385 (4)
S1—C5	1.764 (3)	C23—H231	0.948
C4—H41	0.975	C24—C25	1.409 (5)
C4—H43	0.978	C24—O28	1.372 (4)
C4—H42	0.966	C25—C26	1.378 (5)
C5—C6	1.526 (4)	C25—O31	1.375 (4)
C5—H52	0.975	C26—C27	1.405 (5)
C5—H51	0.977	C26—H261	0.936
C6—N7	1.479 (4)	C27—H271	0.973
C6—C22	1.522 (4)	O28—C29	1.437 (4)
C6—H61	0.972	C29—C30	1.506 (5)
N7—C8	1.393 (4)	C29—H292	0.985
N7—C11	1.400 (4)	C29—H291	0.983
C8—C9	1.472 (5)	C30—H301	0.967
C8—O12	1.224 (4)	C30—H303	0.977
C9—C10	1.385 (4)	C30—H302	0.962
C9—C14	1.386 (5)	O31—C32	1.428 (5)
C10—C11	1.480 (4)	C32—H321	0.977
C10—C17	1.395 (4)	C32—H323	0.976
C11—O13	1.220 (4)	C32—H322	0.960
C14—C15	1.387 (5)	O33—C35	1.240 (15)
C14—H141	0.945	O34—C35	1.327 (19)
C15—C16	1.380 (5)	C35—C36	1.505 (9)
C15—H151	0.964	C36—C36^i	1.4193 (11)
C16—C17	1.403 (5)	C36—C37	1.389 (5)
C16—H161	0.949	C36—C37	1.389 (5)
C17—N18	1.388 (4)	C36—H361	0.966
N18—C19	1.372 (4)	C37—C38	1.386 (11)
N18—H181	0.848	C37—H371	0.956
C19—C20	1.493 (5)	C37—C38	1.386 (11)
C19—O21	1.225 (4)	C37—O40	1.284 (9)
C20—H202	0.973	C38—C38^i	1.342 (16)
C20—H201	0.964	C38—O39	1.311 (13)
C20—H203	0.966	C38—H381	0.954
O2—S1—O3	117.66 (15)	H202—C20—H201	108.2
O2—S1—C4	108.11 (18)	C19—C20—H203	111.8
O3—S1—C4	109.04 (18)	H202—C20—H203	106.9
O2—S1—C5	108.82 (15)	H201—C20—H203	107.0
O3—S1—C5	109.25 (15)	C6—C22—C23	122.5 (3)
C4—S1—C5	102.95 (17)	C6—C22—C27	118.4 (3)
S1—C4—H41	107.9	C23—C22—C27	119.1 (3)
S1—C4—H43	109.5	C22—C23—C24	121.2 (3)
H41—C4—H43	110.2	C22—C23—H231	120.0
S1—C4—H42	107.2	C24—C23—H231	118.8
H41—C4—H42	111.7	C23—C24—C25	119.4 (3)
H43—C4—H42	110.2	C23—C24—O28	124.9 (3)
S1—C5—C6	113.9 (2)	C25—C24—O28	115.7 (3)
S1—C5—H52	106.5	C24—C25—C26	119.5 (3)
C6—C5—H52	108.9	C24—C25—O31	116.0 (3)
S1—C5—H51	108.2	C26—C25—O31	124.5 (3)
C6—C5—H51	108.5	C25—C26—C27	120.4 (3)
H52—C5—H51	110.9	C25—C26—H261	121.6
C5—C6—N7	111.2 (2)	C27—C26—H261	118.0
C5—C6—C22	111.6 (2)	C26—C27—C22	120.5 (3)
N7—C6—C22	112.1 (2)	C26—C27—H271	120.3
C5—C6—H61	106.8	C22—C27—H271	119.2
N7—C6—H61	106.6	C24—O28—C29	116.5 (3)
C22—C6—H61	108.2	O28—C29—C30	108.2 (3)
C6—N7—C8	125.7 (2)	O28—C29—H292	108.8
C6—N7—C11	123.2 (2)	C30—C29—H292	110.6
C8—N7—C11	110.8 (3)	O28—C29—H291	111.5
N7—C8—C9	107.0 (2)	C30—C29—H291	110.3
N7—C8—O12	124.1 (3)	H292—C29—H291	107.4
C9—C8—O12	128.9 (3)	C29—C30—H301	110.3
C8—C9—C10	107.8 (3)	C29—C30—H303	110.4
C8—C9—C14	130.3 (3)	H301—C30—H303	111.5
C10—C9—C14	121.8 (3)	C29—C30—H302	105.4
C9—C10—C11	108.2 (3)	H301—C30—H302	108.9
C9—C10—C17	122.2 (3)	H303—C30—H302	110.3
C11—C10—C17	129.6 (3)	C25—O31—C32	115.9 (3)
C10—C11—N7	106.2 (2)	O31—C32—H321	109.1
C10—C11—O13	128.8 (3)	O31—C32—H323	109.0
N7—C11—O13	125.0 (3)	H321—C32—H323	107.9
C9—C14—C15	116.1 (3)	O31—C32—H322	110.4
C9—C14—H141	120.3	H321—C32—H322	110.4
C15—C14—H141	123.6	H323—C32—H322	109.9
C14—C15—C16	122.7 (3)	O34—C35—O33	121.2 (5)
C14—C15—H151	117.9	O34—C35—C36	114.1 (12)
C16—C15—H151	119.4	O33—C35—C36	109.2 (14)
C15—C16—C17	121.4 (3)	C35—C36—C36^i	120.4 (8)
C15—C16—H161	118.9	C35—C36—C37	121.9 (8)
C17—C16—H161	119.7	C36^i—C36—C37	117.6 (4)
C16—C17—C10	115.7 (3)	C37—C36—H361	120.9
C16—C17—N18	125.8 (3)	C36—C37—C38	123.0 (7)
C10—C17—N18	118.5 (3)	C36—C37—H371	115.9
C17—N18—C19	128.9 (3)	C38—C37—H371	121.2
C17—N18—H181	114.7	C36—C37—C38	123.0 (7)
C19—N18—H181	116.5	C36—C37—O40	123.2 (8)
N18—C19—C20	114.5 (3)	C38—C37—O40	113.8 (9)
N18—C19—O21	123.0 (3)	C37—C38—C38^i	119.5 (4)
C20—C19—O21	122.6 (3)	C37—C38—O39	109.4 (8)
C19—C20—H202	110.4	C38^i—C38—O39	131.1 (7)
C19—C20—H201	112.3	C37—C38—H381	119.4

Symmetry code: (i) −y+1, −x+1, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H52···O21^ii	0.98	2.47	3.437 (6)	169
C5—H51···O12	0.98	2.46	3.091 (6)	122
C5—H51···O12^iii	0.98	2.32	3.155 (6)	143
C16—H161···O21	0.95	2.31	2.908 (6)	120
C27—H271···O2^ii	0.97	2.52	3.292 (6)	136
C27—H271···O39	0.97	2.49	3.108 (6)	121
C26—H261···O3^ii	0.94	2.43	3.352 (6)	168
C32—H321···O21^iv	0.98	2.57	3.521 (6)	164
C23—H231···O12^iii	0.95	2.43	3.380 (6)	176
C30—H301···O40^iii	0.97	2.41	3.264 (6)	148
C4—H43···O2^iii	0.98	2.56	3.381 (6)	142
C4—H42···O13^v	0.97	2.38	3.049 (6)	126
N18—H181···O13	0.85	2.29	2.973 (6)	138
C36—H361···O33	0.97	1.53	2.242 (6)	127
C36—H361···O34	0.97	1.69	2.379 (6)	125

Symmetry codes: (ii) x+1/2, −y+1/2, −z+3/4; (iii) y, x, −z+1; (iv) −y+3/2, x+1/2, z+1/4; (v) −y+1/2, x−1/2, z+1/4.

(apremilast25dihydrbenzoic)

Crystal data

2(C22H24N2O7S)·C7H5O4	Dx = 1.455 Mg m^−3
Mr = 1074.13	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 44445 reflections
a = 12.9170 (1) Å	θ = 4–68°
c = 29.3859 (2) Å	µ = 1.69 mm^−1
V = 4903.00 (8) Å^3	T = 120 K
Z = 4	Block, colorless
F(000) = 2252	0.44 × 0.25 × 0.18 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4287 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.052
ω scans	θmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.50, Tmax = 0.74	k = −15→15
88004 measured reflections	l = −35→35
4443 independent reflections

Refinement

Refinement on F^2	H-atom parameters constrained
Least-squares matrix: full	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.04P)^2 + 5.29P] , where P = (max(Fo^2,0) + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.039	(Δ/σ)max = 0.001
wR(F^2) = 0.102	Δρmax = 0.62 e Å^−3
S = 1.00	Δρmin = −0.35 e Å^−3
4443 reflections	Extinction correction: Larson (1970), Equation 22
354 parameters	Extinction coefficient: 40 (10)
12 restraints	Absolute structure: Flack (1983), 1825 Friedel-pairs
Primary atom site location: Other	Absolute structure parameter: 0.01 (2)
Hydrogen site location: difference Fourier map

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C25	0.5042 (2)	0.1875 (2)	0.55976 (11)	0.0355
C26	0.5615 (2)	0.2033 (2)	0.59904 (9)	0.0330
C27	0.6255 (2)	0.2892 (2)	0.60293 (9)	0.0303
O31	0.43988 (16)	0.10517 (16)	0.55214 (8)	0.0446
C32	0.4307 (3)	0.0329 (2)	0.58867 (11)	0.0476
O33	0.4586 (2)	0.4452 (2)	0.66175 (11)	0.0755
C34	0.4822 (3)	0.4701 (3)	0.70577 (15)	0.0632
C35	0.5621 (3)	0.4127 (3)	0.72862 (14)	0.0677
C36	0.4271 (3)	0.5448 (3)	0.72585 (16)	0.0699
C37	0.3315 (6)	0.5860 (5)	0.7117 (2)	0.0463	0.5000
O38	0.2667 (4)	0.6382 (4)	0.7402 (2)	0.0715	0.5000
O39	0.2990 (4)	0.5734 (5)	0.67285 (18)	0.0671	0.5000
S1	0.83604 (5)	0.59448 (5)	0.53437 (2)	0.0299
O2	0.78956 (16)	0.68728 (15)	0.55285 (7)	0.0375
O3	0.92423 (15)	0.55178 (16)	0.55801 (7)	0.0393
C4	0.8696 (3)	0.6198 (3)	0.47754 (10)	0.0453
C5	0.7395 (2)	0.4977 (2)	0.52909 (8)	0.0278
C6	0.7036 (2)	0.4534 (2)	0.57468 (8)	0.0277
N7	0.65685 (16)	0.53448 (17)	0.60330 (7)	0.0264
C8	0.69483 (19)	0.5627 (2)	0.64622 (8)	0.0267
C9	0.63248 (19)	0.6518 (2)	0.66146 (8)	0.0275
C10	0.5601 (2)	0.6743 (2)	0.62778 (9)	0.0297
C11	0.5748 (2)	0.5990 (2)	0.59047 (9)	0.0293
O12	0.76625 (14)	0.51926 (14)	0.66547 (6)	0.0307
O13	0.52704 (14)	0.59080 (15)	0.55500 (6)	0.0345
C14	0.6370 (2)	0.7079 (2)	0.70173 (9)	0.0299
C15	0.5670 (2)	0.7897 (2)	0.70637 (10)	0.0367
C16	0.4959 (2)	0.8121 (2)	0.67201 (11)	0.0415
C17	0.4901 (2)	0.7541 (2)	0.63219 (10)	0.0365
N18	0.70915 (17)	0.67778 (17)	0.73461 (7)	0.0303
C19	0.7258 (2)	0.7197 (2)	0.77668 (9)	0.0319
C20	0.8005 (2)	0.6589 (2)	0.80570 (9)	0.0395
O21	0.68334 (16)	0.79817 (15)	0.79018 (6)	0.0380
C22	0.6326 (2)	0.3613 (2)	0.56825 (9)	0.0283
C23	0.5745 (2)	0.3460 (2)	0.52862 (9)	0.0329
C24	0.5104 (2)	0.2603 (2)	0.52422 (10)	0.0369
H261	0.5571	0.1546	0.6231	0.0383*
H271	0.6655	0.3005	0.6298	0.0376*
H323	0.3825	−0.0190	0.5770	0.0704*
H322	0.4014	0.0694	0.6149	0.0717*
H321	0.4980	0.0015	0.5955	0.0714*
H351	0.5939	0.3564	0.7140	0.0795*
H41	0.8950	0.5566	0.4642	0.0684*
H42	0.9234	0.6702	0.4786	0.0685*
H43	0.8091	0.6440	0.4608	0.0692*
H52	0.7738	0.4440	0.5111	0.0332*
H51	0.6814	0.5294	0.5124	0.0334*
H61	0.7673	0.4319	0.5907	0.0335*
H151	0.5680	0.8308	0.7328	0.0439*
H161	0.4495	0.8699	0.6763	0.0503*
H171	0.4407	0.7684	0.6099	0.0449*
H201	0.8239	0.7008	0.8304	0.0588*
H202	0.8617	0.6369	0.7882	0.0582*
H203	0.7652	0.5986	0.8177	0.0586*
H231	0.5794	0.3966	0.5049	0.0382*
H181	0.7484	0.6272	0.7266	0.0361*
H381	0.2165	0.6599	0.7239	0.1199*	0.5000
H331	0.3974	0.4647	0.6521	0.1127*
C30	0.3675 (4)	0.2840 (3)	0.41731 (15)	0.0758
C29	0.4506 (3)	0.3149 (2)	0.45068 (11)	0.0496
O28	0.44996 (19)	0.23946 (16)	0.48695 (8)	0.0536
H291	0.4374	0.3821	0.4625	0.0601*
H292	0.5158	0.3144	0.4358	0.0601*
H301	0.3091	0.2580	0.4333	0.0943*
H302	0.3475	0.3425	0.3998	0.0943*
H303	0.3937	0.2317	0.3977	0.0943*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C25	0.0269 (13)	0.0285 (14)	0.0511 (17)	−0.0038 (11)	−0.0029 (12)	0.0100 (12)
C26	0.0307 (14)	0.0343 (14)	0.0341 (14)	0.0031 (11)	0.0044 (11)	0.0082 (12)
C27	0.0301 (14)	0.0309 (14)	0.0301 (13)	0.0035 (10)	0.0014 (11)	0.0033 (11)
O31	0.0421 (12)	0.0303 (10)	0.0613 (13)	−0.0117 (9)	−0.0067 (10)	0.0148 (10)
C32	0.069 (2)	0.0289 (15)	0.0454 (17)	−0.0122 (15)	0.0194 (16)	−0.0002 (13)
O33	0.0679 (18)	0.0644 (17)	0.094 (2)	−0.0030 (14)	0.0027 (17)	0.0007 (16)
C34	0.062 (2)	0.051 (2)	0.076 (3)	−0.0094 (18)	0.011 (2)	0.0029 (19)
C35	0.0409 (19)	0.063 (2)	0.100 (3)	−0.0041 (18)	0.020 (2)	0.024 (2)
C36	0.057 (2)	0.057 (2)	0.096 (3)	0.0130 (19)	−0.006 (2)	−0.002 (2)
C37	0.061 (4)	0.035 (3)	0.043 (3)	0.012 (3)	0.007 (3)	0.013 (3)
O38	0.072 (4)	0.065 (3)	0.078 (4)	0.024 (3)	0.012 (3)	0.020 (3)
O39	0.057 (3)	0.083 (4)	0.062 (3)	−0.016 (3)	0.004 (3)	0.018 (3)
S1	0.0296 (3)	0.0307 (3)	0.0293 (3)	−0.0057 (3)	0.0029 (3)	−0.0027 (3)
O2	0.0447 (11)	0.0311 (10)	0.0365 (10)	−0.0021 (9)	0.0018 (9)	−0.0067 (8)
O3	0.0310 (10)	0.0413 (11)	0.0457 (12)	−0.0038 (8)	−0.0044 (9)	−0.0023 (9)
C4	0.0523 (19)	0.0456 (18)	0.0380 (16)	−0.0105 (14)	0.0155 (14)	0.0005 (13)
C5	0.0286 (13)	0.0298 (13)	0.0249 (12)	−0.0059 (10)	0.0007 (10)	−0.0018 (11)
C6	0.0270 (13)	0.0320 (13)	0.0242 (12)	0.0000 (11)	−0.0017 (10)	0.0003 (10)
N7	0.0237 (10)	0.0342 (12)	0.0212 (10)	−0.0005 (9)	−0.0029 (8)	0.0012 (9)
C8	0.0255 (12)	0.0311 (13)	0.0236 (11)	−0.0050 (10)	−0.0017 (10)	0.0030 (10)
C9	0.0251 (12)	0.0304 (13)	0.0271 (12)	−0.0019 (10)	−0.0013 (10)	0.0043 (10)
C10	0.0267 (13)	0.0322 (14)	0.0301 (12)	−0.0001 (11)	−0.0041 (10)	0.0053 (11)
C11	0.0273 (13)	0.0335 (14)	0.0271 (12)	−0.0021 (11)	−0.0010 (11)	0.0056 (11)
O12	0.0320 (10)	0.0323 (10)	0.0277 (9)	0.0041 (8)	−0.0062 (8)	0.0013 (8)
O13	0.0309 (10)	0.0447 (11)	0.0281 (9)	−0.0007 (9)	−0.0069 (8)	0.0032 (8)
C14	0.0293 (13)	0.0290 (14)	0.0315 (14)	−0.0009 (11)	−0.0029 (11)	0.0028 (11)
C15	0.0333 (15)	0.0378 (15)	0.0391 (15)	0.0076 (12)	−0.0065 (12)	−0.0052 (12)
C16	0.0386 (16)	0.0383 (16)	0.0477 (17)	0.0131 (13)	−0.0109 (13)	−0.0052 (13)
C17	0.0322 (14)	0.0373 (15)	0.0399 (15)	0.0064 (12)	−0.0077 (12)	0.0033 (12)
N18	0.0322 (12)	0.0293 (11)	0.0294 (11)	0.0049 (9)	−0.0061 (9)	−0.0023 (9)
C19	0.0324 (14)	0.0342 (15)	0.0292 (13)	−0.0031 (12)	−0.0014 (11)	0.0013 (11)
C20	0.0489 (17)	0.0384 (16)	0.0312 (14)	0.0025 (14)	−0.0111 (13)	−0.0003 (12)
O21	0.0452 (11)	0.0365 (11)	0.0323 (10)	0.0069 (9)	−0.0019 (9)	−0.0045 (8)
C22	0.0266 (13)	0.0320 (14)	0.0262 (12)	0.0006 (11)	0.0008 (10)	0.0038 (10)
C23	0.0324 (14)	0.0319 (13)	0.0344 (13)	−0.0063 (11)	−0.0071 (11)	0.0112 (12)
C24	0.0331 (15)	0.0340 (14)	0.0434 (15)	−0.0062 (11)	−0.0134 (12)	0.0091 (12)
C30	0.104 (3)	0.0416 (19)	0.082 (3)	−0.021 (2)	−0.063 (2)	0.0170 (18)
C29	0.069 (2)	0.0283 (14)	0.0517 (18)	−0.0106 (14)	−0.0340 (17)	0.0109 (13)
O28	0.0616 (14)	0.0350 (11)	0.0642 (15)	−0.0205 (10)	−0.0373 (12)	0.0205 (10)

Geometric parameters (Å, º)

C25—C26	1.387 (4)	C6—H61	0.987
C25—O31	1.368 (3)	N7—C8	1.402 (3)
C25—C24	1.408 (4)	N7—C11	1.400 (3)
C26—C27	1.388 (4)	C8—C9	1.475 (4)
C26—H261	0.948	C8—O12	1.219 (3)
C27—C22	1.383 (4)	C9—C10	1.392 (3)
C27—H271	0.955	C9—C14	1.389 (4)
O31—C32	1.428 (4)	C10—C11	1.478 (4)
C32—H323	0.977	C10—C17	1.377 (4)
C32—H322	0.979	C11—O13	1.216 (3)
C32—H321	0.980	C14—C15	1.397 (4)
O33—C34	1.367 (5)	C14—N18	1.398 (3)
O33—H331	0.877	C15—C16	1.395 (4)
C34—C35	1.438 (6)	C15—H151	0.940
C34—C36	1.336 (6)	C16—C17	1.392 (4)
C35—C35^i	1.338 (9)	C16—H161	0.966
C35—H351	0.940	C17—H171	0.933
C36—C36^i	1.509 (9)	N18—C19	1.367 (3)
C36—C37	1.409 (8)	N18—H181	0.860
C37—O38	1.364 (8)	C19—C20	1.509 (4)
C37—O39	1.226 (8)	C19—O21	1.218 (3)
O38—O38^i	1.829 (13)	C20—H201	0.955
O38—H381	0.853	C20—H202	0.986
S1—O2	1.447 (2)	C20—H203	0.969
S1—O3	1.444 (2)	C22—C23	1.399 (4)
S1—C4	1.756 (3)	C23—C24	1.389 (4)
S1—C5	1.772 (3)	C23—H231	0.958
C4—H41	0.963	C24—O28	1.371 (3)
C4—H42	0.953	C30—C29	1.508 (4)
C4—H43	0.974	C30—H301	0.950
C5—C6	1.529 (3)	C30—H302	0.950
C5—H52	0.979	C30—H303	0.950
C5—H51	0.986	C29—O28	1.444 (3)
C6—N7	1.473 (3)	C29—H291	0.950
C6—C22	1.515 (4)	C29—H292	0.950
C26—C25—O31	125.1 (3)	N7—C8—C9	106.6 (2)
C26—C25—C24	119.3 (2)	N7—C8—O12	124.3 (2)
O31—C25—C24	115.6 (3)	C9—C8—O12	129.2 (2)
C25—C26—C27	120.3 (2)	C8—C9—C10	108.3 (2)
C25—C26—H261	119.4	C8—C9—C14	130.0 (2)
C27—C26—H261	120.4	C10—C9—C14	121.7 (2)
C26—C27—C22	121.1 (3)	C9—C10—C11	107.7 (2)
C26—C27—H271	120.8	C9—C10—C17	122.0 (3)
C22—C27—H271	118.1	C11—C10—C17	130.3 (2)
C25—O31—C32	115.8 (2)	C10—C11—N7	106.8 (2)
O31—C32—H323	103.7	C10—C11—O13	128.9 (2)
O31—C32—H322	108.0	N7—C11—O13	124.3 (3)
H323—C32—H322	111.2	C9—C14—C15	116.8 (2)
O31—C32—H321	110.6	C9—C14—N18	118.2 (2)
H323—C32—H321	110.7	C15—C14—N18	125.1 (2)
H322—C32—H321	112.4	C14—C15—C16	120.8 (3)
C34—O33—H331	116.1	C14—C15—H151	119.9
O33—C34—C35	118.7 (4)	C16—C15—H151	119.3
O33—C34—C36	118.0 (4)	C15—C16—C17	122.2 (3)
C35—C34—C36	123.3 (4)	C15—C16—H161	118.3
C34—C35—C35^i	119.2 (3)	C17—C16—H161	119.5
C34—C35—H351	119.9	C16—C17—C10	116.5 (3)
C35^i—C35—H351	120.8	C16—C17—H171	121.4
C36^i—C36—C34	117.5 (3)	C10—C17—H171	122.1
C36^i—C36—C37	113.5 (4)	C14—N18—C19	128.3 (2)
C34—C36—C37	127.5 (5)	C14—N18—H181	114.6
C36—C37—O38	122.9 (6)	C19—N18—H181	117.1
C36—C37—O39	121.7 (6)	N18—C19—C20	113.9 (2)
O38—C37—O39	115.4 (6)	N18—C19—O21	123.6 (3)
C37—O38—O38^i	96.5 (5)	C20—C19—O21	122.5 (2)
C37—O38—H381	106.4	C19—C20—H201	109.7
O38^i—O38—H381	117.8	C19—C20—H202	111.6
O2—S1—O3	117.61 (12)	H201—C20—H202	107.9
O2—S1—C4	107.76 (14)	C19—C20—H203	108.9
O3—S1—C4	109.52 (15)	H201—C20—H203	109.1
O2—S1—C5	108.99 (12)	H202—C20—H203	109.6
O3—S1—C5	109.13 (12)	C6—C22—C27	118.5 (2)
C4—S1—C5	102.81 (13)	C6—C22—C23	122.6 (2)
S1—C4—H41	108.2	C27—C22—C23	118.9 (2)
S1—C4—H42	106.0	C22—C23—C24	120.6 (2)
H41—C4—H42	110.2	C22—C23—H231	118.3
S1—C4—H43	110.0	C24—C23—H231	121.0
H41—C4—H43	109.8	C25—C24—C23	119.8 (2)
H42—C4—H43	112.5	C25—C24—O28	115.4 (2)
S1—C5—C6	113.62 (17)	C23—C24—O28	124.8 (2)
S1—C5—H52	103.3	C29—C30—H301	109.7
C6—C5—H52	110.2	C29—C30—H302	109.6
S1—C5—H51	106.6	H301—C30—H302	109.5
C6—C5—H51	111.2	C29—C30—H303	109.1
H52—C5—H51	111.7	H301—C30—H303	109.5
C5—C6—N7	111.0 (2)	H302—C30—H303	109.5
C5—C6—C22	111.6 (2)	C30—C29—O28	107.3 (3)
N7—C6—C22	112.4 (2)	C30—C29—H291	110.6
C5—C6—H61	105.7	O28—C29—H291	110.2
N7—C6—H61	105.6	C30—C29—H292	109.3
C22—C6—H61	110.1	O28—C29—H292	110.0
C6—N7—C8	123.7 (2)	H291—C29—H292	109.5
C6—N7—C11	125.5 (2)	C29—O28—C24	117.0 (2)
C8—N7—C11	110.6 (2)

Symmetry code: (i) −y+1, −x+1, −z+3/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C26—H261···O3^ii	0.95	2.43	3.365 (4)	168
C27—H271···O2^ii	0.96	2.53	3.256 (4)	133
C4—H42···O12^iii	0.95	2.38	3.038 (4)	126
C4—H43···O2^iv	0.97	2.49	3.339 (4)	146
C5—H52···O21^ii	0.98	2.47	3.432 (4)	166
C5—H51···O13^iv	0.99	2.30	3.153 (4)	144
C15—H151···O21	0.94	2.29	2.887 (4)	121
C23—H231···O13^iv	0.96	2.44	3.399 (4)	179
N18—H181···O12	0.86	2.29	2.977 (4)	138
O38—H381···O31^v	0.85	2.27	2.976 (4)	140
O33—H331···O39	0.88	1.99	2.664 (4)	133

Symmetry codes: (ii) −x+3/2, y−1/2, −z+5/4; (iii) y+1/2, −x+3/2, z−1/4; (iv) y, x, −z+1; (v) −x+1/2, y+1/2, −z+5/4.

(Apremilast_4_hydroxybenzoic_acid)

Crystal data

C25.50H25.50N2O8.50S	Dx = 1.429 Mg m^−3
Mr = 528.06	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 42651 reflections
a = 12.9076 (1) Å	θ = 4–67°
c = 29.4670 (2) Å	µ = 1.66 mm^−1
V = 4909.38 (8) Å^3	T = 120 K
Z = 8	Block, colorless
F(000) = 2212	0.27 × 0.14 × 0.12 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4320 reflections with I > 2.0σ(I)
Focussing mirrors monochromator	Rint = 0.042
ω scans	θmax = 67.8°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro (Rigaku Oxford Diffraction, 2017)	h = −15→15
Tmin = 0.59, Tmax = 0.82	k = −15→15
84206 measured reflections	l = −34→35
4433 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.050	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.08P)^2 + 7.51P] , where P = (max(Fo^2,0) + 2Fc^2)/3
wR(F^2) = 0.146	(Δ/σ)max = 0.002
S = 1.03	Δρmax = 0.70 e Å^−3
4433 reflections	Δρmin = −0.86 e Å^−3
356 parameters	Absolute structure: Parsons, Flack & Wagner (2013), 1790 Friedel Pairs
62 restraints	Absolute structure parameter: −0.000 (3)
Primary atom site location: other

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.16345 (7)	0.59577 (7)	0.71378 (3)	0.0259
O2	0.0761 (2)	0.5544 (2)	0.68929 (9)	0.0348
O3	0.2117 (2)	0.6883 (2)	0.69586 (9)	0.0331
C4	0.1252 (3)	0.6203 (3)	0.76999 (14)	0.0402
C5	0.2590 (3)	0.4986 (3)	0.71999 (11)	0.0245
C6	0.2971 (3)	0.4542 (3)	0.67499 (11)	0.0227
C7	0.3061 (3)	0.5631 (3)	0.60378 (11)	0.0223
C8	0.3679 (3)	0.6541 (3)	0.58890 (11)	0.0231
C9	0.4391 (3)	0.6770 (3)	0.62254 (11)	0.0248
C10	0.4245 (3)	0.6011 (3)	0.65965 (11)	0.0240
O11	0.23506 (18)	0.51937 (19)	0.58418 (8)	0.0267
O12	0.47155 (19)	0.5941 (2)	0.69558 (8)	0.0292
C13	0.3636 (3)	0.7094 (3)	0.54847 (11)	0.0235
C14	0.4344 (3)	0.7913 (3)	0.54412 (13)	0.0282
C15	0.5040 (3)	0.8140 (3)	0.57841 (13)	0.0315
C16	0.5091 (3)	0.7566 (3)	0.61870 (12)	0.0291
N17	0.2920 (2)	0.6786 (2)	0.51553 (10)	0.0256
C18	0.2750 (3)	0.7198 (3)	0.47330 (12)	0.0270
C19	0.2013 (3)	0.6583 (3)	0.44478 (12)	0.0346
O20	0.3171 (2)	0.7983 (2)	0.45987 (8)	0.0339
C21	0.3689 (3)	0.3617 (3)	0.68219 (12)	0.0249
C22	0.4241 (3)	0.3472 (3)	0.72271 (12)	0.0253
C23	0.4873 (3)	0.2616 (3)	0.72880 (12)	0.0266
C24	0.4964 (3)	0.1874 (3)	0.69337 (13)	0.0297
C25	0.4427 (3)	0.2028 (3)	0.65355 (13)	0.0313
C26	0.3786 (3)	0.2891 (3)	0.64816 (12)	0.0284
O27	0.5446 (2)	0.2416 (2)	0.76702 (9)	0.0346
C28	0.5407 (3)	0.3192 (3)	0.80235 (13)	0.0359
C29	0.6180 (4)	0.2899 (4)	0.83835 (17)	0.0566
O30	0.5596 (2)	0.1046 (2)	0.70251 (10)	0.0376
C31	0.5765 (4)	0.0347 (4)	0.66559 (16)	0.0550
C36	0.4749 (8)	0.5318 (8)	0.0446 (4)	0.1352
C37	0.5577 (7)	0.5855 (6)	0.0219 (3)	0.1129
N6	0.3445 (2)	0.5345 (2)	0.64627 (9)	0.0221
H42	0.3183	0.5297	0.7353	0.0272*
H41	0.2299	0.4433	0.7385	0.0271*
H51	0.2372	0.4282	0.6583	0.0253*
H142	0.1775	0.6995	0.4198	0.0500*
H141	0.1435	0.6375	0.4633	0.0502*
H143	0.2360	0.5976	0.4342	0.0502*
H151	0.4345	0.8312	0.5177	0.0332*
H161	0.5494	0.8696	0.5742	0.0340*
H171	0.5577	0.7721	0.6411	0.0341*
H221	0.3431	0.2975	0.6206	0.0309*
H231	0.4483	0.1554	0.6298	0.0329*
H261	0.6198	−0.0212	0.6762	0.0759*
H263	0.6090	0.0698	0.6406	0.0760*
H262	0.5109	0.0066	0.6560	0.0761*
H281	0.4189	0.3968	0.7457	0.0281*
H302	0.4723	0.3241	0.8152	0.0432*
H301	0.5598	0.3859	0.7895	0.0430*
H311	0.6235	0.3460	0.8596	0.0831*
H313	0.5941	0.2282	0.8534	0.0831*
H312	0.6844	0.2764	0.8242	0.0830*
H321	0.1797	0.6469	0.7884	0.0571*
H323	0.0691	0.6691	0.7698	0.0569*
H322	0.0997	0.5572	0.7831	0.0571*
H111	0.253 (4)	0.635 (4)	0.5211 (14)	0.0297*
O38	0.5951 (12)	0.6724 (11)	0.0394 (6)	0.1911	0.5000
C35	0.4281 (7)	0.4543 (8)	0.0208 (3)	0.1418
C34	0.3418 (12)	0.4012 (13)	0.0397 (6)	0.1752	0.5000
O33	0.2852 (14)	0.3291 (15)	0.0124 (8)	0.1970	0.5000
O39	0.3048 (15)	0.4311 (15)	0.0793 (9)	0.2207	0.5000
H371	0.5934	0.6391	0.0371	0.1482*	0.5000
H361	0.4628	0.5550	0.0747	0.1769*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0259 (4)	0.0280 (4)	0.0239 (4)	0.0048 (3)	0.0027 (3)	0.0006 (3)
O2	0.0293 (13)	0.0354 (14)	0.0398 (15)	0.0033 (11)	−0.0038 (11)	−0.0001 (12)
O3	0.0376 (14)	0.0290 (13)	0.0328 (13)	0.0020 (11)	0.0019 (11)	0.0057 (11)
C4	0.044 (2)	0.044 (2)	0.032 (2)	0.0053 (18)	0.0152 (17)	−0.0055 (17)
C5	0.0261 (17)	0.0267 (17)	0.0207 (15)	0.0025 (13)	0.0008 (13)	0.0021 (13)
C6	0.0236 (16)	0.0249 (16)	0.0196 (15)	−0.0008 (14)	−0.0011 (13)	−0.0021 (13)
C7	0.0219 (16)	0.0261 (17)	0.0189 (15)	0.0011 (13)	−0.0002 (13)	−0.0024 (13)
C8	0.0225 (16)	0.0238 (16)	0.0230 (16)	0.0037 (13)	0.0009 (13)	−0.0058 (13)
C9	0.0230 (16)	0.0270 (17)	0.0243 (16)	0.0029 (13)	−0.0019 (13)	−0.0063 (14)
C10	0.0229 (17)	0.0259 (17)	0.0231 (17)	0.0024 (14)	−0.0001 (13)	−0.0056 (14)
O11	0.0275 (13)	0.0297 (13)	0.0229 (11)	−0.0051 (10)	−0.0049 (10)	−0.0017 (10)
O12	0.0266 (13)	0.0385 (14)	0.0224 (12)	0.0004 (11)	−0.0063 (10)	−0.0036 (11)
C13	0.0211 (16)	0.0247 (17)	0.0245 (17)	0.0026 (13)	0.0003 (13)	−0.0040 (13)
C14	0.0265 (18)	0.0253 (17)	0.0330 (19)	0.0031 (14)	−0.0007 (14)	−0.0006 (14)
C15	0.0277 (18)	0.0273 (19)	0.040 (2)	−0.0061 (15)	−0.0038 (15)	0.0021 (16)
C16	0.0255 (17)	0.0321 (19)	0.0298 (18)	0.0004 (15)	−0.0055 (14)	−0.0051 (15)
N17	0.0278 (15)	0.0226 (15)	0.0265 (15)	−0.0064 (12)	−0.0051 (12)	0.0017 (12)
C18	0.0274 (17)	0.0305 (19)	0.0233 (17)	0.0054 (15)	0.0022 (14)	−0.0014 (14)
C19	0.042 (2)	0.037 (2)	0.0251 (17)	−0.0018 (18)	−0.0072 (16)	0.0015 (16)
O20	0.0390 (15)	0.0344 (14)	0.0284 (13)	−0.0054 (12)	0.0005 (11)	0.0051 (11)
C21	0.0237 (17)	0.0257 (18)	0.0253 (16)	−0.0030 (14)	0.0009 (13)	−0.0011 (13)
C22	0.0253 (17)	0.0242 (17)	0.0265 (17)	0.0008 (13)	−0.0019 (13)	−0.0047 (14)
C23	0.0251 (17)	0.0215 (16)	0.0332 (18)	0.0001 (13)	−0.0013 (14)	−0.0015 (14)
C24	0.0252 (18)	0.0242 (17)	0.040 (2)	0.0020 (14)	0.0068 (15)	0.0004 (15)
C25	0.034 (2)	0.0275 (18)	0.0319 (18)	−0.0024 (15)	0.0076 (15)	−0.0055 (15)
C26	0.0314 (19)	0.0293 (18)	0.0243 (17)	−0.0034 (14)	0.0024 (14)	−0.0036 (14)
O27	0.0353 (14)	0.0288 (13)	0.0397 (14)	0.0040 (11)	−0.0114 (12)	−0.0031 (11)
C28	0.045 (2)	0.0247 (18)	0.0380 (19)	0.0012 (16)	−0.0156 (18)	−0.0021 (16)
C29	0.075 (4)	0.039 (2)	0.056 (3)	0.011 (2)	−0.033 (3)	−0.005 (2)
O30	0.0416 (15)	0.0261 (13)	0.0450 (16)	0.0112 (12)	0.0070 (13)	−0.0024 (12)
C31	0.086 (4)	0.035 (2)	0.043 (2)	0.022 (2)	0.031 (2)	0.0048 (19)
C36	0.119 (5)	0.113 (5)	0.174 (7)	0.054 (4)	−0.022 (5)	0.047 (5)
C37	0.104 (4)	0.083 (4)	0.152 (7)	0.021 (4)	−0.045 (4)	0.036 (4)
N6	0.0225 (13)	0.0254 (14)	0.0183 (13)	−0.0006 (11)	−0.0023 (11)	−0.0029 (11)
O38	0.192 (10)	0.150 (8)	0.231 (11)	−0.007 (9)	−0.034 (9)	0.007 (9)
C35	0.104 (5)	0.109 (5)	0.212 (9)	0.027 (5)	−0.057 (5)	0.073 (5)
C34	0.144 (8)	0.149 (8)	0.233 (12)	0.005 (8)	−0.049 (8)	0.067 (8)
O33	0.179 (9)	0.177 (9)	0.235 (14)	−0.004 (10)	−0.046 (8)	0.050 (8)
O39	0.195 (11)	0.198 (11)	0.269 (14)	0.008 (11)	−0.045 (11)	0.037 (11)

Geometric parameters (Å, º)

S1—O2	1.441 (3)	C19—H143	0.955
S1—O3	1.447 (3)	C21—C22	1.403 (5)
S1—C4	1.757 (4)	C21—C26	1.378 (5)
S1—C5	1.768 (3)	C22—C23	1.385 (5)
C4—H321	0.952	C22—H281	0.935
C4—H323	0.959	C23—C24	1.421 (5)
C4—H322	0.959	C23—O27	1.371 (4)
C5—C6	1.527 (4)	C24—C25	1.377 (6)
C5—H42	0.975	C24—O30	1.371 (4)
C5—H41	0.974	C25—C26	1.397 (5)
C6—C21	1.526 (5)	C25—H231	0.931
C6—N6	1.472 (4)	C26—H221	0.938
C6—H51	0.977	O27—C28	1.445 (4)
C7—C8	1.486 (5)	C28—C29	1.505 (6)
C7—O11	1.222 (4)	C28—H302	0.962
C7—N6	1.396 (4)	C28—H301	0.973
C8—C9	1.384 (5)	C29—H311	0.959
C8—C13	1.390 (5)	C29—H313	0.962
C9—C10	1.480 (5)	C29—H312	0.968
C9—C16	1.373 (5)	O30—C31	1.430 (5)
C10—O12	1.224 (4)	C31—H261	0.965
C10—N6	1.400 (4)	C31—H263	0.962
C13—C14	1.403 (5)	C31—H262	0.964
C13—N17	1.398 (4)	C36—C37	1.438 (13)
C14—C15	1.383 (5)	C36—C35	1.363 (14)
C14—H151	0.933	C36—H361	0.949
C15—C16	1.401 (5)	C37—C37^i	1.386 (16)
C15—H161	0.934	C37—O38	1.327 (8)
C16—H171	0.933	C37—H371	0.946
N17—C18	1.371 (5)	C35—C35^i	1.32 (2)
N17—H111	0.77 (5)	C35—C34	1.421 (9)
C18—C19	1.497 (5)	C34—O33	1.43 (2)
C18—O20	1.216 (5)	C34—O39	1.32 (3)
C19—H142	0.960	O33—O33^i	1.09 (4)
C19—H141	0.963
O2—S1—O3	117.40 (16)	H141—C19—H143	108.6
O2—S1—C4	108.6 (2)	C6—C21—C22	122.1 (3)
O3—S1—C4	108.41 (19)	C6—C21—C26	119.1 (3)
O2—S1—C5	109.53 (16)	C22—C21—C26	118.8 (3)
O3—S1—C5	108.85 (16)	C21—C22—C23	121.1 (3)
C4—S1—C5	103.07 (18)	C21—C22—H281	119.2
S1—C4—H321	113.2	C23—C22—H281	119.7
S1—C4—H323	108.9	C22—C23—C24	119.4 (3)
H321—C4—H323	109.0	C22—C23—O27	125.0 (3)
S1—C4—H322	108.8	C24—C23—O27	115.6 (3)
H321—C4—H322	109.3	C23—C24—C25	119.2 (3)
H323—C4—H322	107.5	C23—C24—O30	115.4 (3)
S1—C5—C6	113.7 (2)	C25—C24—O30	125.4 (3)
S1—C5—H42	107.7	C24—C25—C26	120.7 (3)
C6—C5—H42	107.6	C24—C25—H231	120.4
S1—C5—H41	108.0	C26—C25—H231	119.0
C6—C5—H41	109.6	C25—C26—C21	120.9 (3)
H42—C5—H41	110.3	C25—C26—H221	118.7
C5—C6—C21	111.7 (3)	C21—C26—H221	120.4
C5—C6—N6	111.6 (3)	C23—O27—C28	116.3 (3)
C21—C6—N6	112.3 (3)	O27—C28—C29	108.1 (3)
C5—C6—H51	108.1	O27—C28—H302	111.1
C21—C6—H51	106.4	C29—C28—H302	110.4
N6—C6—H51	106.4	O27—C28—H301	108.9
C8—C7—O11	128.9 (3)	C29—C28—H301	109.2
C8—C7—N6	106.4 (3)	H302—C28—H301	109.1
O11—C7—N6	124.6 (3)	C28—C29—H311	108.6
C7—C8—C9	108.3 (3)	C28—C29—H313	108.6
C7—C8—C13	129.6 (3)	H311—C29—H313	110.5
C9—C8—C13	122.1 (3)	C28—C29—H312	109.2
C8—C9—C10	107.7 (3)	H311—C29—H312	110.5
C8—C9—C16	122.5 (3)	H313—C29—H312	109.4
C10—C9—C16	129.8 (3)	C24—O30—C31	115.7 (3)
C9—C10—O12	128.7 (3)	O30—C31—H261	108.2
C9—C10—N6	107.0 (3)	O30—C31—H263	110.7
O12—C10—N6	124.4 (3)	H261—C31—H263	110.4
C8—C13—C14	116.0 (3)	O30—C31—H262	109.1
C8—C13—N17	118.4 (3)	H261—C31—H262	108.8
C14—C13—N17	125.6 (3)	H263—C31—H262	109.6
C13—C14—C15	121.1 (3)	C37—C36—C35	116.3 (9)
C13—C14—H151	119.5	C37—C36—H361	113.9
C15—C14—H151	119.4	C35—C36—H361	129.7
C14—C15—C16	122.5 (3)	C36—C37—C37^i	120.0 (5)
C14—C15—H161	118.2	C36—C37—O38	119.8 (2)
C16—C15—H161	119.3	C37^i—C37—O38	119.1 (6)
C15—C16—C9	115.8 (3)	C36—C37—H371	119.6
C15—C16—H171	121.3	C37^i—C37—H371	120.3
C9—C16—H171	123.0	O38—C37—H371	10.9
C13—N17—C18	128.7 (3)	C6—N6—C10	125.2 (3)
C13—N17—H111	119 (3)	C6—N6—C7	123.7 (3)
C18—N17—H111	112 (3)	C10—N6—C7	110.6 (3)
N17—C18—C19	113.9 (3)	C36—C35—C35^i	123.6 (6)
N17—C18—O20	123.2 (3)	C36—C35—C34	120.0 (7)
C19—C18—O20	122.9 (3)	C35^i—C35—C34	116.2 (5)
C18—C19—H142	110.0	C35—C34—O33	119.7 (8)
C18—C19—H141	108.8	C35—C34—O39	119.2 (5)
H142—C19—H141	110.0	O33—C34—O39	120.2 (2)
C18—C19—H143	108.7	C34—O33—O33^i	116.9 (14)
H142—C19—H143	110.7

Symmetry code: (i) y, x, −z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H42···O12	0.98	2.44	3.093 (7)	124
C5—H42···O12^ii	0.98	2.33	3.152 (7)	141
C5—H41···O20^iii	0.97	2.49	3.453 (7)	171
C14—H151···O20	0.93	2.32	2.910 (7)	121
C26—H221···O3^iii	0.94	2.52	3.276 (7)	138
C26—H221···O38^iv	0.94	2.55	3.261 (7)	132
C25—H231···O2^iii	0.93	2.44	3.349 (7)	165
C31—H261···O20^v	0.97	2.54	3.493 (7)	169
C22—H281···O12^ii	0.94	2.43	3.366 (7)	179
C4—H321···O3^ii	0.95	2.54	3.392 (7)	149
C4—H323···O11^vi	0.96	2.37	3.042 (7)	126
N17—H111···O11	0.770	2.396	2.976 (7)	133 (4)

Symmetry codes: (ii) −y+1, −x+1, −z+3/2; (iii) −x+1/2, y−1/2, −z+5/4; (iv) −x+1, −y+1, z+1/2; (v) −y+3/2, x−1/2, z+1/4; (vi) −y+1/2, x+1/2, z+1/4.

(apremilastanisol)

Crystal data

C25.50H28.00N2O7.50S	Dx = 1.394 Mg m^−3
Mr = 514.58	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 39017 reflections
a = 12.8885 (1) Å	θ = 4–67°
c = 29.5227 (1) Å	µ = 1.62 mm^−1
V = 4904.12 (8) Å^3	T = 120 K
Z = 8	Block, colorless
F(000) = 2167.988	0.22 × 0.21 × 0.14 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4342 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.031
ω scans	θmax = 67.6°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.15, Tmax = 0.80	k = −15→15
61003 measured reflections	l = −35→35
4440 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.032	Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)^2]^2 Ai are: 421. 573. 219.
wR(F^2) = 0.046	(Δ/σ)max = 0.003
S = 1.10	Δρmax = 0.76 e Å^−3
4440 reflections	Δρmin = −0.35 e Å^−3
333 parameters	Absolute structure: Flack (1983), 1823 Friedel-pairs
8 restraints	Absolute structure parameter: 0.010 (16)
Primary atom site location: structure-invariant direct methods

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.40256 (4)	0.16203 (4)	0.463269 (18)	0.0232
O2	0.31052 (12)	0.21085 (12)	0.44540 (5)	0.0294
O3	0.44436 (12)	0.07517 (12)	0.43880 (5)	0.0319
C4	0.37759 (19)	0.12371 (19)	0.51958 (7)	0.0342
C5	0.50031 (16)	0.25750 (16)	0.47003 (6)	0.0211
C6	0.54509 (16)	0.29622 (16)	0.42514 (6)	0.0201
N7	0.46407 (13)	0.34358 (13)	0.39649 (5)	0.0194
C8	0.43542 (15)	0.30528 (16)	0.35393 (6)	0.0189
C9	0.34475 (16)	0.36737 (15)	0.33910 (7)	0.0192
C10	0.32183 (16)	0.43851 (16)	0.37257 (7)	0.0210
C11	0.39785 (16)	0.42352 (15)	0.41017 (7)	0.0200
O12	0.47862 (11)	0.23406 (11)	0.33434 (4)	0.0238
O13	0.40403 (12)	0.46926 (11)	0.44562 (5)	0.0257
C14	0.28966 (16)	0.36325 (15)	0.29875 (7)	0.0207
C15	0.20800 (16)	0.43430 (16)	0.29406 (7)	0.0240
C16	0.18482 (17)	0.50396 (17)	0.32862 (7)	0.0279
C17	0.24149 (17)	0.50854 (17)	0.36869 (7)	0.0254
N18	0.32062 (13)	0.29195 (13)	0.26578 (5)	0.0220
C19	0.28006 (17)	0.27599 (17)	0.22352 (7)	0.0239
C20	0.34240 (18)	0.20240 (18)	0.19486 (7)	0.0301
O21	0.20137 (11)	0.31796 (12)	0.21001 (5)	0.0299
C22	0.63718 (16)	0.36884 (16)	0.43235 (7)	0.0208
C23	0.65132 (16)	0.42295 (16)	0.47321 (7)	0.0219
C24	0.73707 (16)	0.48613 (16)	0.47911 (7)	0.0225
C25	0.81033 (17)	0.49640 (17)	0.44397 (7)	0.0252
C26	0.79545 (17)	0.44337 (17)	0.40400 (7)	0.0267
C27	0.70926 (16)	0.37950 (17)	0.39837 (7)	0.0241
O28	0.75666 (12)	0.54271 (12)	0.51777 (5)	0.0290
C29	0.67935 (17)	0.53842 (19)	0.55282 (7)	0.0311
C30	0.7105 (2)	0.6129 (2)	0.58952 (9)	0.0508
O31	0.89353 (12)	0.55971 (12)	0.45321 (5)	0.0326
C32	0.96278 (19)	0.5778 (2)	0.41645 (8)	0.0484
O40	1.1500 (4)	1.1031 (4)	0.0325 (2)	0.1058	0.5000
C41	1.1917 (3)	1.1917 (3)	0.000000 (10)	0.1315
C42	1.0686 (3)	1.0398 (3)	0.02287 (16)	0.1111
C43	1.0150 (4)	0.9624 (4)	0.04385 (16)	0.1049
C44	0.9384 (3)	0.9125 (2)	0.02191 (11)	0.0636
H201	0.3072	0.1856	0.1686	0.0451*
H203	0.4061	0.2383	0.1863	0.0460*
H202	0.3612	0.1424	0.2117	0.0451*
H151	0.1665	0.4351	0.2670	0.0289*
H161	0.1294	0.5517	0.3240	0.0327*
H171	0.2283	0.5542	0.3920	0.0307*
H303	0.6595	0.6143	0.6135	0.0750*
H301	0.7770	0.5964	0.6020	0.0746*
H302	0.7144	0.6816	0.5772	0.0737*
H291	0.6751	0.4656	0.5659	0.0365*
H292	0.6095	0.5571	0.5402	0.0371*
H321	1.0171	0.6221	0.4286	0.0719*
H323	0.9951	0.5128	0.4068	0.0728*
H322	0.9302	0.6090	0.3909	0.0729*
H271	0.7007	0.3432	0.3707	0.0279*
H261	0.8443	0.4495	0.3805	0.0308*
H231	0.6019	0.4167	0.4969	0.0252*
H61	0.5706	0.2361	0.4085	0.0235*
H52	0.5538	0.2256	0.4887	0.0244*
H51	0.4698	0.3157	0.4866	0.0236*
H42	0.3548	0.1843	0.5365	0.0501*
H41	0.4422	0.0927	0.5319	0.0510*
H43	0.3203	0.0721	0.5173	0.0500*
H441	0.8989	0.8591	0.0369	0.0781*
H431	1.0334	0.9456	0.0734	0.1265*
H181	0.3734	0.2539	0.2739	0.0315*
H414	1.2488	1.2254	0.0140	0.1514*	0.5000
H416	1.1381	1.2407	−0.0055	0.1514*	0.5000
H415	1.2134	1.1620	−0.0279	0.1514*	0.5000
H421	1.1238	1.0744	0.0379	0.1287*	0.5000

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0245 (3)	0.0241 (3)	0.0210 (2)	−0.0049 (2)	−0.0014 (2)	0.0018 (2)
O2	0.0249 (8)	0.0348 (9)	0.0286 (8)	−0.0028 (7)	−0.0045 (7)	0.0034 (7)
O3	0.0356 (9)	0.0255 (9)	0.0346 (9)	−0.0048 (7)	−0.0011 (7)	−0.0040 (7)
C4	0.0387 (15)	0.0371 (14)	0.0267 (12)	−0.0062 (10)	0.0024 (11)	0.0093 (10)
C5	0.0225 (11)	0.0230 (11)	0.0178 (10)	−0.0034 (8)	−0.0014 (9)	−0.0008 (9)
C6	0.0229 (11)	0.0205 (11)	0.0170 (10)	0.0013 (9)	0.0003 (9)	−0.0013 (9)
N7	0.0202 (9)	0.0203 (9)	0.0177 (8)	0.0001 (7)	0.0013 (7)	−0.0015 (7)
C8	0.0197 (11)	0.0205 (11)	0.0166 (9)	−0.0022 (8)	0.0030 (8)	0.0008 (8)
C9	0.0205 (11)	0.0180 (10)	0.0193 (10)	−0.0019 (8)	0.0039 (9)	0.0008 (8)
C10	0.0223 (11)	0.0196 (11)	0.0213 (10)	−0.0037 (8)	0.0039 (9)	−0.0002 (8)
C11	0.0205 (11)	0.0189 (11)	0.0205 (10)	−0.0013 (9)	0.0041 (9)	0.0003 (9)
O12	0.0251 (8)	0.0254 (8)	0.0210 (7)	0.0043 (6)	0.0019 (6)	−0.0033 (6)
O13	0.0328 (9)	0.0251 (8)	0.0193 (7)	−0.0006 (7)	0.0019 (7)	−0.0061 (6)
C14	0.0200 (11)	0.0210 (11)	0.0212 (11)	−0.0032 (9)	0.0034 (9)	−0.0007 (8)
C15	0.0226 (11)	0.0242 (12)	0.0253 (11)	−0.0006 (9)	−0.0008 (9)	0.0017 (9)
C16	0.0229 (12)	0.0240 (12)	0.0369 (13)	0.0037 (10)	−0.0001 (10)	−0.0010 (10)
C17	0.0284 (12)	0.0224 (12)	0.0255 (11)	0.0026 (10)	0.0058 (9)	−0.0037 (9)
N18	0.0212 (9)	0.0245 (10)	0.0203 (9)	0.0029 (8)	−0.0013 (7)	−0.0027 (8)
C19	0.0262 (12)	0.0243 (12)	0.0211 (11)	−0.0065 (9)	0.0023 (9)	0.0011 (9)
C20	0.0333 (13)	0.0350 (13)	0.0220 (11)	0.0015 (11)	0.0006 (10)	−0.0067 (10)
O21	0.0296 (9)	0.0356 (9)	0.0244 (8)	0.0043 (7)	−0.0064 (7)	−0.0002 (7)
C22	0.0203 (11)	0.0217 (11)	0.0205 (10)	0.0019 (9)	0.0006 (8)	0.0015 (8)
C23	0.0208 (11)	0.0222 (11)	0.0227 (10)	−0.0003 (8)	0.0047 (9)	0.0002 (9)
C24	0.0219 (11)	0.0217 (11)	0.0239 (10)	0.0010 (8)	−0.0006 (9)	−0.0014 (9)
C25	0.0205 (11)	0.0263 (12)	0.0289 (11)	−0.0007 (9)	0.0002 (9)	0.0061 (10)
C26	0.0218 (12)	0.0323 (13)	0.0259 (11)	0.0016 (9)	0.0040 (10)	0.0045 (10)
C27	0.0267 (12)	0.0261 (12)	0.0195 (10)	0.0039 (9)	0.0014 (9)	0.0001 (9)
O28	0.0268 (8)	0.0305 (9)	0.0296 (8)	−0.0053 (7)	0.0020 (7)	−0.0087 (7)
C29	0.0247 (12)	0.0396 (14)	0.0289 (11)	−0.0011 (11)	0.0024 (10)	−0.0112 (11)
C30	0.0380 (16)	0.072 (2)	0.0425 (15)	−0.0098 (14)	0.0061 (13)	−0.0269 (15)
O31	0.0249 (8)	0.0380 (9)	0.0350 (9)	−0.0114 (7)	0.0003 (7)	0.0046 (7)
C32	0.0299 (14)	0.081 (2)	0.0345 (14)	−0.0232 (14)	−0.0057 (11)	0.0229 (14)
O40	0.072 (4)	0.080 (4)	0.166 (6)	0.012 (3)	0.011 (4)	−0.054 (4)
C41	0.091 (3)	0.091 (3)	0.213 (9)	−0.050 (4)	0.056 (4)	−0.056 (4)
C42	0.039 (2)	0.071 (3)	0.224 (6)	−0.004 (2)	0.035 (3)	−0.088 (3)
C43	0.089 (3)	0.114 (4)	0.111 (4)	0.063 (3)	−0.015 (3)	−0.059 (3)
C44	0.058 (2)	0.0409 (17)	0.092 (2)	0.0093 (15)	0.0241 (18)	−0.0159 (18)

Geometric parameters (Å, º)

S1—O2	1.4427 (16)	C22—C27	1.374 (3)
S1—O3	1.4371 (16)	C23—C24	1.384 (3)
S1—C4	1.764 (2)	C23—H231	0.950
S1—C5	1.772 (2)	C24—C25	1.409 (3)
C4—H42	0.973	C24—O28	1.378 (2)
C4—H41	0.993	C25—C26	1.377 (3)
C4—H43	0.996	C25—O31	1.375 (3)
C5—C6	1.529 (3)	C26—C27	1.393 (3)
C5—H52	0.974	C26—H261	0.939
C5—H51	0.978	C27—H271	0.948
C6—N7	1.476 (2)	O28—C29	1.438 (2)
C6—C22	1.526 (3)	C29—C30	1.502 (3)
C6—H61	0.976	C29—H291	1.016
N7—C8	1.400 (2)	C29—H292	1.004
N7—C11	1.397 (3)	C30—H303	0.967
C8—C9	1.482 (3)	C30—H301	0.956
C8—O12	1.219 (2)	C30—H302	0.958
C9—C10	1.380 (3)	O31—C32	1.424 (3)
C9—C14	1.388 (3)	C32—H321	0.971
C10—C11	1.493 (3)	C32—H323	0.978
C10—C17	1.378 (3)	C32—H322	0.953
C11—O13	1.204 (2)	O40—C41	1.584 (7)
C14—C15	1.402 (3)	O40—C42	1.359 (6)
C14—N18	1.397 (3)	C41—H415^i	0.950
C15—C16	1.391 (3)	C41—H416^i	0.950
C15—H151	0.962	C41—H414^i	0.950
C16—C17	1.392 (3)	C41—H414	0.950
C16—H161	0.953	C41—H416	0.950
C17—H171	0.921	C41—H415	0.950
N18—C19	1.368 (3)	C42—C42^i	1.449 (10)
N18—H181	0.872	C42—C43	1.363 (6)
C19—C20	1.504 (3)	C42—H421	0.950
C19—O21	1.217 (3)	C43—C44	1.344 (5)
C20—H201	0.924	C43—H431	0.929
C20—H203	0.976	C44—C44^i	1.377 (7)
C20—H202	0.951	C44—H441	0.964
C22—C23	1.405 (3)
O2—S1—O3	117.66 (9)	C25—C24—O28	115.94 (18)
O2—S1—C4	108.46 (11)	C24—C25—C26	119.4 (2)
O3—S1—C4	108.90 (11)	C24—C25—O31	115.61 (19)
O2—S1—C5	108.84 (10)	C26—C25—O31	125.0 (2)
O3—S1—C5	109.32 (10)	C25—C26—C27	120.5 (2)
C4—S1—C5	102.59 (10)	C25—C26—H261	119.8
S1—C4—H42	108.4	C27—C26—H261	119.8
S1—C4—H41	107.7	C26—C27—C22	120.7 (2)
H42—C4—H41	112.9	C26—C27—H271	119.2
S1—C4—H43	104.9	C22—C27—H271	120.1
H42—C4—H43	110.4	C24—O28—C29	116.67 (16)
H41—C4—H43	112.2	O28—C29—C30	108.01 (19)
S1—C5—C6	113.40 (13)	O28—C29—H291	110.2
S1—C5—H52	105.9	C30—C29—H291	109.3
C6—C5—H52	111.2	O28—C29—H292	110.1
S1—C5—H51	107.6	C30—C29—H292	110.8
C6—C5—H51	109.6	H291—C29—H292	108.3
H52—C5—H51	109.0	C29—C30—H303	111.0
C5—C6—N7	111.39 (17)	C29—C30—H301	112.1
C5—C6—C22	111.88 (16)	H303—C30—H301	109.3
N7—C6—C22	112.12 (16)	C29—C30—H302	109.3
C5—C6—H61	107.8	H303—C30—H302	107.2
N7—C6—H61	106.1	H301—C30—H302	107.8
C22—C6—H61	107.2	C25—O31—C32	115.75 (18)
C6—N7—C8	123.73 (16)	O31—C32—H321	105.5
C6—N7—C11	124.84 (16)	O31—C32—H323	110.4
C8—N7—C11	111.00 (16)	H321—C32—H323	107.7
N7—C8—C9	106.42 (16)	O31—C32—H322	113.3
N7—C8—O12	124.81 (18)	H321—C32—H322	111.2
C9—C8—O12	128.77 (18)	H323—C32—H322	108.6
C8—C9—C10	108.41 (18)	C41—O40—C42	124.6 (6)
C8—C9—C14	129.51 (18)	O40—C41—O40^i	83.0 (5)
C10—C9—C14	122.04 (19)	O40—C41—H415^i	63.4
C9—C10—C11	107.81 (17)	O40^i—C41—H415^i	109.5
C9—C10—C17	122.43 (19)	O40—C41—H416^i	66.3
C11—C10—C17	129.76 (19)	O40^i—C41—H416^i	109.7
C10—C11—N7	106.33 (16)	H415^i—C41—H416^i	109.5
C10—C11—O13	128.77 (19)	O40—C41—H414^i	167.7
N7—C11—O13	124.9 (2)	O40^i—C41—H414^i	109.2
C9—C14—C15	116.35 (19)	H415^i—C41—H414^i	109.5
C9—C14—N18	118.50 (18)	H416^i—C41—H414^i	109.5
C15—C14—N18	125.13 (19)	O40—C41—H414	109.2
C14—C15—C16	120.7 (2)	O40^i—C41—H414	167.7
C14—C15—H151	120.4	H415^i—C41—H414	78.4
C16—C15—H151	118.9	H416^i—C41—H414	75.0
C15—C16—C17	122.5 (2)	H414^i—C41—H414	58.7
C15—C16—H161	118.2	O40—C41—H416	109.7
C17—C16—H161	119.2	O40^i—C41—H416	66.3
C16—C17—C10	115.9 (2)	H415^i—C41—H416	70.1
C16—C17—H171	124.4	H416^i—C41—H416	175.0
C10—C17—H171	119.6	H414^i—C41—H416	75.0
C14—N18—C19	128.69 (18)	O40—C41—H415	109.5
C14—N18—H181	113.7	O40^i—C41—H415	63.4
C19—N18—H181	117.6	H415^i—C41—H415	171.3
N18—C19—C20	113.82 (19)	H416^i—C41—H415	70.1
N18—C19—O21	123.4 (2)	H414^i—C41—H415	78.4
C20—C19—O21	122.77 (19)	H414—C41—H416	109.5
C19—C20—H201	111.0	H414—C41—H415	109.5
C19—C20—H203	107.2	H416—C41—H415	109.5
H201—C20—H203	107.9	C42^i—C42—O40	103.8 (4)
C19—C20—H202	110.9	C42^i—C42—C43	118.8 (3)
H201—C20—H202	111.9	O40—C42—C43	137.4 (6)
H203—C20—H202	107.8	C42^i—C42—H421	120.6
C6—C22—C23	121.66 (18)	O40—C42—H421	16.8
C6—C22—C27	119.02 (18)	C43—C42—H421	120.7
C23—C22—C27	119.30 (19)	C42—C43—C44	120.2 (5)
C22—C23—C24	120.25 (19)	C42—C43—H431	117.9
C22—C23—H231	120.3	C44—C43—H431	121.9
C24—C23—H231	119.5	C44^i—C44—C43	121.0 (3)
C23—C24—C25	119.86 (19)	C44^i—C44—H441	118.5
C23—C24—O28	124.20 (19)	C43—C44—H441	120.5

Symmetry code: (i) y, x, −z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C32—H321···O21^ii	0.97	2.53	3.490 (3)	167
C27—H271···O2^iii	0.95	2.51	3.275 (3)	138
C26—H261···O3^iii	0.94	2.44	3.354 (3)	164
C23—H231···O13^iv	0.95	2.41	3.363 (3)	177
C5—H52···O21^iii	0.97	2.49	3.454 (3)	168
C5—H51···O13	0.98	2.47	3.084 (3)	120
C5—H51···O13^iv	0.98	2.30	3.151 (3)	145
C4—H42···O2^iv	0.97	2.53	3.389 (3)	148
N18—H181···O12	0.87	2.26	2.967 (3)	139

Symmetry codes: (ii) −y+3/2, x+1/2, z+1/4; (iii) x+1/2, −y+1/2, −z+3/4; (iv) y, x, −z+1.

(apremilast_brombenzen)

Crystal data

C25H26.50Br0.50N2O7S	Dx = 1.465 Mg m^−3
Mr = 539.01	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 55255 reflections
a = 12.8625 (1) Å	θ = 4–68°
c = 29.5499 (1) Å	µ = 2.55 mm^−1
V = 4888.85 (8) Å^3	T = 120 K
Z = 8	Block, colorless
F(000) = 2240	0.22 × 0.17 × 0.09 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4321 reflections with I > 2.0σ(I)
Focussing mirrors monochromator	Rint = 0.033
ω scans	θmax = 67.6°, θmin = 3.8°
Absorption correction: multi-scan CrysAlisPro (Rigaku Oxford Diffraction, 2017)	h = −15→15
Tmin = 0.67, Tmax = 0.79	k = −15→15
92129 measured reflections	l = −35→34
4425 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.074	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.15P)^2 + 15.58P] , where P = (max(Fo^2,0) + 2Fc^2)/3
wR(F^2) = 0.215	(Δ/σ)max = 0.006
S = 0.99	Δρmax = 2.25 e Å^−3
4425 reflections	Δρmin = −2.35 e Å^−3
325 parameters	Absolute structure: Parsons, Flack & Wagner (2013), 1780 Friedel Pairs
61 restraints	Absolute structure parameter: 0.011 (3)
Primary atom site location: structure-invariant direct methods

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.83868 (10)	0.40196 (10)	0.71396 (4)	0.0198
O2	0.9262 (3)	0.4443 (3)	0.68985 (14)	0.0269
O3	0.7907 (3)	0.3089 (3)	0.69612 (13)	0.0267
C4	0.8756 (5)	0.3784 (5)	0.7703 (2)	0.0307
C5	0.7433 (4)	0.4998 (4)	0.72018 (17)	0.0192
C6	0.7045 (4)	0.5437 (4)	0.67501 (16)	0.0192
N7	0.6574 (3)	0.4625 (3)	0.64648 (14)	0.0180
C8	0.6953 (4)	0.4339 (4)	0.60392 (17)	0.0178
C9	0.6322 (4)	0.3446 (4)	0.58907 (17)	0.0172
C10	0.5610 (4)	0.3210 (4)	0.62282 (17)	0.0185
C11	0.5758 (4)	0.3968 (4)	0.65972 (17)	0.0183
O12	0.7671 (3)	0.4773 (3)	0.58431 (12)	0.0215
O13	0.5299 (3)	0.4039 (3)	0.69567 (12)	0.0232
C14	0.6354 (4)	0.2889 (4)	0.54829 (17)	0.0196
C15	0.5644 (4)	0.2079 (4)	0.54326 (19)	0.0238
C16	0.4939 (4)	0.1842 (4)	0.57841 (19)	0.0249
C17	0.4904 (4)	0.2405 (4)	0.61865 (19)	0.0226
N18	0.7073 (4)	0.3209 (4)	0.51536 (14)	0.0209
C19	0.7227 (4)	0.2800 (4)	0.47335 (18)	0.0219
O20	0.6815 (3)	0.2008 (3)	0.45990 (13)	0.0283
C21	0.7980 (5)	0.3432 (5)	0.44479 (19)	0.0293
C22	0.6315 (4)	0.6365 (4)	0.68198 (18)	0.0191
C23	0.5778 (4)	0.6515 (4)	0.72214 (17)	0.0198
C24	0.5134 (4)	0.7373 (4)	0.72775 (17)	0.0195
C25	0.5036 (4)	0.8105 (4)	0.69241 (19)	0.0224
C26	0.5571 (4)	0.7943 (4)	0.65259 (18)	0.0213
C27	0.6207 (4)	0.7079 (4)	0.64726 (17)	0.0198
O28	0.4569 (3)	0.7572 (3)	0.76625 (13)	0.0259
C29	0.4606 (5)	0.6795 (4)	0.80141 (19)	0.0275
C30	0.3818 (6)	0.7089 (5)	0.8372 (2)	0.0418
O31	0.4410 (3)	0.8935 (3)	0.70102 (13)	0.0259
C32	0.4271 (5)	0.9649 (4)	0.6646 (2)	0.0307
Br33	0.58460 (12)	0.58460 (12)	0.5000	0.1840
C36	0.3310 (8)	0.3946 (7)	0.5364 (3)	0.0706
C35	0.4151 (7)	0.4717 (7)	0.5375 (3)	0.0828
C34	0.4820 (7)	0.4820 (7)	0.5000	0.0917
C37	0.3281 (7)	0.3281 (7)	0.5000	0.0700
H41	0.8992	0.4403	0.7848	0.0452*
H43	0.8189	0.3487	0.7863	0.0451*
H52	0.7739	0.5544	0.7373	0.0201*
H51	0.6855	0.4723	0.7363	0.0198*
H61	0.7635	0.5687	0.6580	0.0213*
H151	0.5636	0.1698	0.5168	0.0266*
H161	0.4481	0.1287	0.5747	0.0271*
H171	0.4431	0.2266	0.6411	0.0258*
H212	0.8166	0.3036	0.4188	0.0428*
H211	0.8591	0.3582	0.4627	0.0428*
H213	0.7653	0.4063	0.4365	0.0433*
H231	0.5845	0.6034	0.7451	0.0228*
H261	0.5503	0.8427	0.6295	0.0253*
H271	0.6557	0.6986	0.6204	0.0225*
H291	0.5286	0.6784	0.8157	0.0329*
H292	0.4421	0.6115	0.7886	0.0330*
H301	0.3754	0.6534	0.8581	0.0591*
H302	0.4033	0.7714	0.8524	0.0590*
H303	0.3163	0.7190	0.8238	0.0588*
H321	0.3779	1.0176	0.6726	0.0448*
H322	0.4924	0.9981	0.6580	0.0447*
H323	0.4036	0.9294	0.6381	0.0446*
H361	0.2815	0.3904	0.5593	0.0792*
H371	0.2773	0.2773	0.5000	0.0785*
H42	0.9313	0.3284	0.7707	0.0447*
H351	0.4210	0.5130	0.5641	0.0909*
H181	0.7502	0.3672	0.5240	0.0246*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0201 (6)	0.0204 (6)	0.0190 (6)	0.0050 (5)	−0.0022 (5)	−0.0012 (5)
O2	0.0213 (19)	0.030 (2)	0.030 (2)	0.0053 (16)	0.0044 (16)	−0.0021 (17)
O3	0.031 (2)	0.0223 (19)	0.0266 (19)	0.0016 (17)	−0.0019 (17)	−0.0043 (16)
C4	0.035 (3)	0.033 (3)	0.024 (3)	0.005 (3)	−0.009 (2)	0.002 (2)
C5	0.019 (3)	0.020 (2)	0.019 (2)	0.0044 (19)	0.000 (2)	−0.003 (2)
C6	0.023 (3)	0.021 (3)	0.014 (2)	0.000 (2)	0.0017 (19)	−0.002 (2)
N7	0.019 (2)	0.021 (2)	0.0139 (19)	−0.0025 (18)	0.0045 (17)	0.0011 (17)
C8	0.020 (2)	0.016 (2)	0.018 (2)	0.0006 (19)	0.000 (2)	0.0030 (19)
C9	0.019 (2)	0.018 (2)	0.015 (2)	0.0011 (19)	0.0004 (19)	0.0031 (19)
C10	0.015 (2)	0.021 (3)	0.019 (2)	0.0047 (19)	0.0027 (19)	0.005 (2)
C11	0.015 (2)	0.021 (2)	0.019 (3)	0.001 (2)	−0.001 (2)	0.004 (2)
O12	0.0230 (19)	0.0223 (19)	0.0191 (17)	−0.0023 (15)	0.0037 (15)	0.0005 (14)
O13	0.0199 (19)	0.030 (2)	0.0194 (18)	0.0003 (16)	0.0052 (15)	0.0017 (16)
C14	0.020 (3)	0.021 (3)	0.017 (2)	0.002 (2)	0.002 (2)	0.004 (2)
C15	0.026 (3)	0.020 (3)	0.026 (3)	0.001 (2)	0.001 (2)	−0.002 (2)
C16	0.021 (3)	0.023 (3)	0.030 (3)	−0.003 (2)	0.006 (2)	0.002 (2)
C17	0.020 (3)	0.022 (3)	0.026 (3)	0.002 (2)	0.005 (2)	0.004 (2)
N18	0.025 (2)	0.021 (2)	0.016 (2)	−0.0024 (19)	0.0030 (18)	−0.0024 (17)
C19	0.025 (3)	0.021 (3)	0.020 (3)	0.004 (2)	0.000 (2)	0.001 (2)
O20	0.032 (2)	0.029 (2)	0.0243 (19)	−0.0066 (18)	0.0029 (17)	−0.0056 (17)
C21	0.033 (3)	0.035 (3)	0.020 (3)	−0.002 (3)	0.004 (2)	−0.004 (2)
C22	0.021 (3)	0.018 (3)	0.019 (2)	−0.003 (2)	0.0001 (19)	0.0036 (19)
C23	0.022 (3)	0.020 (2)	0.018 (2)	0.002 (2)	0.001 (2)	0.004 (2)
C24	0.022 (3)	0.019 (3)	0.017 (2)	0.002 (2)	0.0018 (19)	−0.0004 (19)
C25	0.022 (3)	0.019 (3)	0.026 (3)	0.000 (2)	−0.002 (2)	0.002 (2)
C26	0.025 (3)	0.020 (3)	0.020 (2)	−0.002 (2)	−0.001 (2)	0.006 (2)
C27	0.023 (3)	0.022 (3)	0.015 (2)	0.001 (2)	0.001 (2)	0.004 (2)
O28	0.030 (2)	0.024 (2)	0.0236 (19)	0.0094 (16)	0.0106 (16)	0.0057 (15)
C29	0.038 (3)	0.022 (3)	0.023 (3)	0.003 (2)	0.012 (2)	0.003 (2)
C30	0.060 (5)	0.032 (3)	0.033 (3)	0.008 (3)	0.021 (3)	0.006 (3)
O31	0.032 (2)	0.0198 (19)	0.0261 (19)	0.0098 (16)	−0.0003 (17)	0.0024 (16)
C32	0.047 (4)	0.017 (3)	0.028 (3)	0.010 (2)	−0.010 (3)	0.002 (2)
Br33	0.0888 (10)	0.0888 (10)	0.374 (5)	−0.0231 (12)	−0.1006 (19)	0.1006 (19)
C36	0.066 (4)	0.059 (4)	0.086 (5)	0.011 (4)	−0.008 (4)	0.039 (4)
C35	0.072 (5)	0.060 (4)	0.117 (5)	0.012 (4)	−0.041 (4)	0.025 (4)
C34	0.055 (3)	0.055 (3)	0.165 (6)	−0.003 (4)	−0.044 (4)	0.044 (4)
C37	0.061 (4)	0.061 (4)	0.088 (6)	−0.006 (5)	−0.027 (4)	0.027 (4)

Geometric parameters (Å, º)

S1—O2	1.440 (4)	C21—H212	0.951
S1—O3	1.446 (4)	C21—H211	0.966
S1—C4	1.759 (6)	C21—H213	0.946
S1—C5	1.767 (5)	C22—C23	1.387 (7)
C4—H41	0.954	C22—C27	1.383 (7)
C4—H43	0.949	C23—C24	1.389 (7)
C4—H42	0.963	C23—H231	0.922
C5—C6	1.533 (7)	C24—C25	1.412 (7)
C5—H52	0.951	C24—O28	1.374 (6)
C5—H51	0.951	C25—C26	1.379 (8)
C6—N7	1.472 (7)	C25—O31	1.361 (7)
C6—C22	1.533 (7)	C26—C27	1.389 (8)
C6—H61	0.966	C26—H261	0.928
N7—C8	1.398 (7)	C27—H271	0.919
N7—C11	1.403 (7)	O28—C29	1.443 (7)
C8—C9	1.473 (7)	C29—C30	1.514 (8)
C8—O12	1.225 (7)	C29—H291	0.971
C9—C10	1.388 (7)	C29—H292	0.981
C9—C14	1.403 (8)	C30—H301	0.946
C10—C11	1.475 (7)	C30—H302	0.961
C10—C17	1.383 (8)	C30—H303	0.940
C11—O13	1.219 (7)	O31—C32	1.426 (7)
C14—C15	1.394 (8)	C32—H321	0.958
C14—N18	1.405 (7)	C32—H322	0.962
C15—C16	1.412 (8)	C32—H323	0.955
C15—H151	0.922	Br33—C34	1.867 (13)
C16—C17	1.393 (8)	C36—C35	1.468 (13)
C16—H161	0.932	C36—C37	1.374 (13)
C17—H171	0.918	C36—H361	0.931
N18—C19	1.362 (7)	C35—C34	1.409 (9)
N18—H181	0.852	C35—H351	0.951
C19—O20	1.215 (7)	C37—H371	0.924
C19—C21	1.520 (8)
O2—S1—O3	117.8 (2)	C19—C21—H212	108.8
O2—S1—C4	108.9 (3)	C19—C21—H211	108.8
O3—S1—C4	108.5 (3)	H212—C21—H211	110.1
O2—S1—C5	109.0 (2)	C19—C21—H213	108.6
O3—S1—C5	109.3 (2)	H212—C21—H213	111.3
C4—S1—C5	102.2 (3)	H211—C21—H213	109.3
S1—C4—H41	111.5	C6—C22—C23	121.9 (5)
S1—C4—H43	109.5	C6—C22—C27	118.6 (5)
H41—C4—H43	111.0	C23—C22—C27	119.5 (5)
S1—C4—H42	109.1	C22—C23—C24	120.6 (5)
H41—C4—H42	108.3	C22—C23—H231	119.2
H43—C4—H42	107.4	C24—C23—H231	120.1
S1—C5—C6	113.4 (3)	C23—C24—C25	119.6 (5)
S1—C5—H52	107.1	C23—C24—O28	124.2 (5)
C6—C5—H52	109.0	C25—C24—O28	116.2 (5)
S1—C5—H51	109.2	C24—C25—C26	119.1 (5)
C6—C5—H51	108.6	C24—C25—O31	115.9 (5)
H52—C5—H51	109.4	C26—C25—O31	125.0 (5)
C5—C6—N7	111.8 (4)	C25—C26—C27	120.8 (5)
C5—C6—C22	111.7 (4)	C25—C26—H261	118.6
N7—C6—C22	112.2 (4)	C27—C26—H261	120.6
C5—C6—H61	108.6	C26—C27—C22	120.4 (5)
N7—C6—H61	105.2	C26—C27—H271	119.3
C22—C6—H61	107.0	C22—C27—H271	120.3
C6—N7—C8	123.9 (4)	C24—O28—C29	116.7 (4)
C6—N7—C11	125.1 (4)	O28—C29—C30	107.9 (5)
C8—N7—C11	110.7 (4)	O28—C29—H291	110.7
N7—C8—C9	106.3 (4)	C30—C29—H291	107.6
N7—C8—O12	124.7 (5)	O28—C29—H292	109.4
C9—C8—O12	129.0 (5)	C30—C29—H292	109.2
C8—C9—C10	108.7 (4)	H291—C29—H292	111.9
C8—C9—C14	129.7 (5)	C29—C30—H301	108.9
C10—C9—C14	121.7 (5)	C29—C30—H302	110.1
C9—C10—C11	107.5 (5)	H301—C30—H302	110.6
C9—C10—C17	122.2 (5)	C29—C30—H303	109.9
C11—C10—C17	130.2 (5)	H301—C30—H303	107.5
C10—C11—N7	106.8 (4)	H302—C30—H303	109.9
C10—C11—O13	129.2 (5)	C25—O31—C32	116.0 (4)
N7—C11—O13	124.1 (5)	O31—C32—H321	110.6
C9—C14—C15	117.0 (5)	O31—C32—H322	109.2
C9—C14—N18	117.7 (5)	H321—C32—H322	108.3
C15—C14—N18	125.2 (5)	O31—C32—H323	110.5
C14—C15—C16	120.2 (5)	H321—C32—H323	109.3
C14—C15—H151	119.6	H322—C32—H323	108.8
C16—C15—H151	120.2	C35—C36—C37	117.3 (7)
C15—C16—C17	122.5 (5)	C35—C36—H361	121.8
C15—C16—H161	118.9	C37—C36—H361	120.9
C17—C16—H161	118.6	C36—C35—C34	119.7 (8)
C16—C17—C10	116.3 (5)	C36—C35—H351	117.0
C16—C17—H171	122.6	C34—C35—H351	123.3
C10—C17—H171	121.1	Br33—C34—C35	119.8 (6)
C14—N18—C19	127.9 (5)	Br33—C34—C35^i	119.8 (6)
C14—N18—H181	115.0	C35—C34—C35^i	120.3 (11)
C19—N18—H181	116.8	C36^i—C37—C36	125.3 (12)
N18—C19—O20	123.9 (5)	C36^i—C37—H371	117.3
N18—C19—C21	113.1 (5)	C36—C37—H371	117.3
O20—C19—C21	123.0 (5)

Symmetry code: (i) y, x, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H43···O3^ii	0.95	2.49	3.367 (8)	154
C5—H52···O20^iii	0.95	2.51	3.448 (8)	168
C5—H51···O13	0.95	2.49	3.095 (8)	121
C5—H51···O13^ii	0.95	2.32	3.149 (8)	146
C15—H151···O20	0.92	2.30	2.889 (8)	121
C23—H231···O13^ii	0.92	2.46	3.377 (8)	177
C26—H261···O2^iii	0.93	2.45	3.351 (8)	164
C27—H271···O3^iii	0.92	2.52	3.256 (8)	137
C32—H321···O20^iv	0.96	2.59	3.502 (8)	160
C4—H42···O12^v	0.96	2.35	3.034 (8)	127
N18—H181···O12	0.85	2.29	2.965 (8)	137

Symmetry codes: (ii) −y+1, −x+1, −z+3/2; (iii) −x+3/2, y+1/2, −z+5/4; (iv) −y+1/2, x+1/2, z+1/4; (v) −y+3/2, x−1/2, z+1/4.

(Apremilast_chlorbenzen)

Crystal data

C33.33H35.33Cl0.67N2.67O9.33S1.33	Dx = 1.411 Mg m^−3
Mr = 689.05	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 29828 reflections
a = 12.8788 (1) Å	θ = 3–68°
c = 29.3261 (1) Å	µ = 2.11 mm^−1
V = 4864.13 (8) Å^3	T = 120 K
Z = 6	Block, colorless
F(000) = 2168	0.36 × 0.22 × 0.17 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4293 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.035
ω scans	θmax = 67.6°, θmin = 4.6°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.27, Tmax = 0.70	k = −13→15
45672 measured reflections	l = −35→33
4375 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.032	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.06P)^2 + 2.22P] , where P = (max(Fo^2,0) + 2Fc^2)/3
wR(F^2) = 0.090	(Δ/σ)max = 0.001
S = 0.99	Δρmax = 0.74 e Å^−3
4375 reflections	Δρmin = −0.48 e Å^−3
353 parameters	Absolute structure: Flack (1983), 1792 Friedel-pairs
120 restraints	Absolute structure parameter: −0.002 (15)
Primary atom site location: Other

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.83338 (4)	0.59281 (4)	0.535290 (15)	0.0209
O2	0.78621 (12)	0.68571 (11)	0.55365 (5)	0.0285
O3	0.92110 (11)	0.55006 (12)	0.55933 (5)	0.0297
C4	0.86911 (19)	0.61702 (18)	0.47858 (7)	0.0337
C5	0.73663 (15)	0.49608 (15)	0.52942 (6)	0.0198
C6	0.70029 (14)	0.45069 (15)	0.57500 (6)	0.0192
N7	0.65371 (12)	0.53190 (12)	0.60392 (5)	0.0181
C8	0.69400 (14)	0.56082 (14)	0.64653 (6)	0.0178
C9	0.63211 (14)	0.65106 (14)	0.66189 (6)	0.0186
C10	0.55915 (14)	0.67363 (15)	0.62873 (6)	0.0194
C11	0.57215 (14)	0.59752 (14)	0.59125 (6)	0.0188
O12	0.76558 (10)	0.51740 (11)	0.66566 (4)	0.0228
O13	0.52369 (11)	0.58965 (11)	0.55585 (4)	0.0242
C14	0.63792 (14)	0.70680 (14)	0.70243 (6)	0.0188
C15	0.56687 (15)	0.78869 (15)	0.70766 (7)	0.0228
C16	0.49488 (15)	0.81118 (16)	0.67379 (7)	0.0260
C17	0.48837 (16)	0.75369 (15)	0.63339 (7)	0.0242
N18	0.71178 (12)	0.67619 (12)	0.73485 (5)	0.0202
C19	0.73064 (15)	0.71863 (15)	0.77692 (6)	0.0224
C20	0.80639 (17)	0.65822 (17)	0.80517 (7)	0.0282
O21	0.68941 (12)	0.79803 (11)	0.79057 (5)	0.0274
C22	0.62850 (14)	0.35783 (15)	0.56808 (6)	0.0195
C23	0.57242 (14)	0.34285 (15)	0.52768 (6)	0.0210
C24	0.50920 (15)	0.25649 (15)	0.52240 (6)	0.0215
C25	0.50205 (15)	0.18262 (15)	0.55782 (7)	0.0221
C26	0.55710 (16)	0.19813 (15)	0.59768 (7)	0.0232
C27	0.62053 (16)	0.28568 (15)	0.60251 (6)	0.0222
O28	0.45004 (12)	0.23601 (10)	0.48454 (5)	0.0271
C29	0.44727 (18)	0.31466 (15)	0.44969 (7)	0.0271
C30	0.3625 (2)	0.28688 (19)	0.41678 (8)	0.0422
O31	0.43929 (12)	0.09896 (11)	0.54950 (5)	0.0282
C32	0.42404 (19)	0.02912 (17)	0.58662 (7)	0.0340
Cl40	0.3979 (2)	0.4897 (2)	0.67626 (9)	0.1147	0.5000
C41	0.4632 (4)	0.4996 (5)	0.72509 (16)	0.0617	0.5000
H41	0.9238	0.6717	0.4809	0.0513*
C42	0.4285 (7)	0.5696 (9)	0.7571 (3)	0.0663	0.5000
H42	0.8978	0.5548	0.4642	0.0511*
C43	0.4824 (5)	0.5842 (4)	0.7959 (2)	0.0648	0.5000
H43	0.8076	0.6434	0.4616	0.0510*
C44	0.5634 (4)	0.5149 (4)	0.80783 (16)	0.0551	0.5000
C45	0.5933 (5)	0.4392 (6)	0.7779 (2)	0.0561	0.5000
C46	0.5427 (7)	0.4306 (6)	0.7359 (2)	0.0651	0.5000
H51	0.7686	0.4414	0.5113	0.0239*
H52	0.6834	0.5294	0.5119	0.0233*
H61	0.7613	0.4273	0.5929	0.0229*
H151	0.5665	0.8275	0.7340	0.0263*
H161	0.4489	0.8669	0.6781	0.0298*
H171	0.4387	0.7697	0.6105	0.0292*
H181	0.7542	0.6188	0.7266	0.0244*
H201	0.8310	0.7022	0.8297	0.0428*
H202	0.7697	0.5988	0.8163	0.0434*
H203	0.8654	0.6394	0.7872	0.0428*
H231	0.5785	0.3923	0.5038	0.0253*
H261	0.5525	0.1503	0.6211	0.0271*
H271	0.6602	0.2964	0.6295	0.0271*
H291	0.4298	0.3823	0.4638	0.0330*
H292	0.5158	0.3196	0.4342	0.0329*
H301	0.3524	0.3411	0.3952	0.0622*
H302	0.2967	0.2741	0.4324	0.0631*
H303	0.3809	0.2264	0.3984	0.0625*
H321	0.3778	−0.0231	0.5767	0.0493*
H322	0.3932	0.0638	0.6117	0.0496*
H323	0.4891	−0.0016	0.5955	0.0506*
H421	0.3779	0.6196	0.7486	0.0766*	0.5000
H431	0.4608	0.6358	0.8178	0.0804*	0.5000
H441	0.5975	0.5205	0.8370	0.0684*	0.5000
H451	0.6483	0.3931	0.7855	0.0661*	0.5000
H461	0.5627	0.3785	0.7147	0.0759*	0.5000

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0216 (2)	0.0217 (2)	0.0196 (2)	−0.00418 (18)	0.00156 (18)	−0.00186 (18)
O2	0.0348 (8)	0.0228 (7)	0.0281 (7)	−0.0012 (6)	0.0017 (6)	−0.0050 (6)
O3	0.0239 (7)	0.0321 (8)	0.0333 (8)	−0.0032 (6)	−0.0042 (6)	−0.0012 (6)
C4	0.0364 (12)	0.0375 (12)	0.0273 (10)	−0.0063 (9)	0.0109 (9)	0.0021 (9)
C5	0.0204 (9)	0.0217 (9)	0.0171 (8)	−0.0027 (7)	−0.0003 (7)	−0.0031 (7)
C6	0.0194 (9)	0.0204 (9)	0.0179 (9)	0.0020 (7)	−0.0007 (7)	−0.0001 (7)
N7	0.0184 (7)	0.0210 (8)	0.0148 (7)	−0.0005 (6)	−0.0016 (6)	0.0012 (6)
C8	0.0191 (9)	0.0192 (9)	0.0151 (8)	−0.0030 (7)	0.0002 (7)	0.0031 (7)
C9	0.0185 (9)	0.0180 (9)	0.0193 (9)	−0.0030 (7)	0.0003 (7)	0.0034 (7)
C10	0.0190 (9)	0.0199 (9)	0.0194 (8)	−0.0020 (7)	−0.0008 (7)	0.0034 (7)
C11	0.0188 (9)	0.0193 (9)	0.0183 (9)	−0.0021 (7)	−0.0003 (7)	0.0029 (7)
O12	0.0232 (7)	0.0242 (7)	0.0209 (6)	0.0047 (5)	−0.0044 (5)	0.0009 (5)
O13	0.0226 (7)	0.0300 (7)	0.0201 (6)	0.0001 (6)	−0.0048 (5)	0.0013 (6)
C14	0.0187 (9)	0.0171 (9)	0.0204 (9)	−0.0027 (7)	0.0003 (7)	0.0026 (7)
C15	0.0234 (10)	0.0218 (9)	0.0233 (9)	−0.0007 (8)	−0.0014 (7)	−0.0025 (8)
C16	0.0224 (10)	0.0227 (10)	0.0329 (11)	0.0055 (8)	−0.0021 (8)	−0.0015 (8)
C17	0.0218 (10)	0.0241 (10)	0.0268 (10)	0.0030 (8)	−0.0050 (8)	0.0020 (8)
N18	0.0229 (8)	0.0193 (8)	0.0185 (7)	0.0025 (6)	−0.0025 (6)	−0.0008 (6)
C19	0.0228 (10)	0.0244 (10)	0.0201 (9)	−0.0032 (8)	0.0005 (7)	0.0010 (8)
C20	0.0316 (11)	0.0312 (11)	0.0218 (9)	0.0011 (9)	−0.0065 (8)	0.0012 (8)
O21	0.0328 (8)	0.0270 (7)	0.0224 (7)	0.0040 (6)	−0.0012 (6)	−0.0047 (6)
C22	0.0191 (9)	0.0197 (9)	0.0198 (9)	0.0032 (7)	0.0013 (7)	−0.0003 (7)
C23	0.0215 (9)	0.0207 (9)	0.0206 (9)	0.0010 (7)	−0.0015 (7)	0.0040 (7)
C24	0.0227 (9)	0.0201 (9)	0.0216 (9)	0.0020 (7)	−0.0027 (7)	0.0000 (7)
C25	0.0221 (10)	0.0179 (9)	0.0262 (10)	−0.0004 (7)	0.0021 (8)	0.0017 (8)
C26	0.0269 (10)	0.0215 (10)	0.0213 (9)	0.0032 (8)	0.0027 (8)	0.0045 (7)
C27	0.0253 (10)	0.0241 (10)	0.0174 (9)	0.0014 (8)	−0.0019 (7)	−0.0001 (7)
O28	0.0307 (8)	0.0225 (7)	0.0280 (7)	−0.0051 (6)	−0.0103 (6)	0.0045 (6)
C29	0.0359 (11)	0.0214 (10)	0.0241 (9)	0.0007 (8)	−0.0101 (8)	0.0026 (8)
C30	0.0600 (16)	0.0285 (12)	0.0381 (13)	−0.0051 (11)	−0.0250 (12)	0.0030 (10)
O31	0.0345 (8)	0.0202 (7)	0.0298 (7)	−0.0071 (6)	−0.0012 (6)	0.0033 (6)
C32	0.0520 (14)	0.0217 (10)	0.0282 (11)	−0.0088 (10)	0.0117 (10)	−0.0006 (8)
Cl40	0.1142 (19)	0.142 (2)	0.0877 (15)	−0.0859 (18)	−0.0338 (14)	0.0533 (15)
C41	0.052 (3)	0.065 (3)	0.069 (4)	−0.033 (3)	0.004 (3)	0.026 (3)
C42	0.050 (4)	0.060 (4)	0.088 (6)	−0.007 (2)	0.037 (4)	0.043 (4)
C43	0.071 (4)	0.050 (3)	0.073 (4)	−0.018 (3)	0.018 (3)	−0.004 (3)
C44	0.050 (3)	0.044 (3)	0.070 (4)	−0.022 (2)	0.013 (3)	0.012 (3)
C45	0.038 (3)	0.045 (3)	0.085 (4)	−0.013 (2)	0.015 (3)	0.036 (3)
C46	0.059 (4)	0.057 (5)	0.079 (6)	−0.027 (4)	0.023 (4)	0.017 (4)

Geometric parameters (Å, º)

S1—O2	1.4459 (15)	C25—C26	1.382 (3)
S1—O3	1.4411 (15)	C25—O31	1.369 (2)
S1—C4	1.754 (2)	C26—C27	1.400 (3)
S1—C5	1.7703 (19)	C26—H261	0.923
C4—H41	0.998	C27—H271	0.952
C4—H42	0.979	O28—C29	1.440 (2)
C4—H43	0.995	C29—C30	1.500 (3)
C5—C6	1.532 (2)	C29—H291	0.990
C5—H51	0.973	C29—H292	0.995
C5—H52	0.958	C30—H301	0.952
C6—N7	1.474 (2)	C30—H302	0.977
C6—C22	1.525 (3)	C30—H303	0.975
C6—H61	0.993	O31—C32	1.426 (2)
N7—C8	1.403 (2)	C32—H321	0.944
N7—C11	1.399 (2)	C32—H322	0.948
C8—C9	1.479 (3)	C32—H323	0.963
C8—O12	1.215 (2)	Cl40—H441^i	1.587
C9—C10	1.383 (3)	Cl40—C44^i	1.395 (6)
C9—C14	1.391 (3)	Cl40—H431^i	0.791
C10—C11	1.482 (3)	Cl40—C41	1.666 (5)
C10—C17	1.383 (3)	C41—C41^i	1.611 (9)
C11—O13	1.216 (2)	C41—C45^i	1.738 (7)
C14—C15	1.405 (3)	C41—C44^i	1.292 (8)
C14—N18	1.401 (2)	C41—C42^i	1.144 (8)
C15—C16	1.389 (3)	C41—C43^i	0.897 (6)
C15—H151	0.921	C41—C42	1.376 (7)
C16—C17	1.400 (3)	C41—C46	1.393 (6)
C16—H161	0.939	C42—H421^i	0.932
C17—H171	0.950	C42—C43^i	1.701 (13)
N18—C19	1.371 (2)	C42—C43	1.347 (7)
N18—H181	0.950	C42—H421	0.950
C19—C20	1.498 (3)	C43—C44	1.416 (6)
C19—O21	1.220 (2)	C43—H431	0.965
C20—H201	0.969	C44—C46^i	1.483 (10)
C20—H202	0.957	C44—C45	1.367 (6)
C20—H203	0.956	C44—H441	0.965
C22—C23	1.401 (3)	C45—C45^i	1.741 (14)
C22—C27	1.376 (3)	C45—C46	1.3992 (10)
C23—C24	1.387 (3)	C45—H451	0.950
C23—H231	0.950	C46—C46^i	0.961 (13)
C24—C25	1.411 (3)	C46—H461	0.950
C24—O28	1.372 (2)	H451—H461^i	0.665
O2—S1—O3	117.60 (9)	H322—C32—H323	110.3
O2—S1—C4	108.44 (10)	H441^i—Cl40—C44^i	37.0
O3—S1—C4	109.04 (10)	H441^i—Cl40—H431^i	171.2
O2—S1—C5	108.84 (9)	C44^i—Cl40—H431^i	139.7
O3—S1—C5	109.30 (9)	H441^i—Cl40—C41	86.0
C4—S1—C5	102.57 (10)	C44^i—Cl40—C41	49.0 (3)
S1—C4—H41	104.2	H431^i—Cl40—C41	91.4
S1—C4—H42	111.3	C41^i—C41—Cl40	162.4 (3)
H41—C4—H42	109.9	C41^i—C41—C45^i	92.0 (3)
S1—C4—H43	109.0	Cl40—C41—C45^i	105.6 (4)
H41—C4—H43	110.8	C41^i—C41—C44^i	143.1 (4)
H42—C4—H43	111.3	Cl40—C41—C44^i	54.5 (3)
S1—C5—C6	113.49 (13)	C45^i—C41—C44^i	51.1 (3)
S1—C5—H51	105.3	C41^i—C41—C42^i	57.0 (5)
C6—C5—H51	109.2	Cl40—C41—C42^i	105.6 (5)
S1—C5—H52	103.9	C45^i—C41—C42^i	148.0 (7)
C6—C5—H52	114.9	C44^i—C41—C42^i	158.4 (7)
H51—C5—H52	109.5	C41^i—C41—C43^i	138.5 (7)
C5—C6—N7	110.83 (15)	Cl40—C41—C43^i	24.0 (5)
C5—C6—C22	111.60 (15)	C45^i—C41—C43^i	129.4 (8)
N7—C6—C22	112.72 (15)	C44^i—C41—C43^i	78.3 (6)
C5—C6—H61	109.7	C42^i—C41—C43^i	81.6 (6)
N7—C6—H61	103.5	C41^i—C41—C42	44.2 (2)
C22—C6—H61	108.2	Cl40—C41—C42	118.2 (4)
C6—N7—C8	123.38 (15)	C45^i—C41—C42	136.1 (4)
C6—N7—C11	125.56 (14)	C44^i—C41—C42	172.7 (5)
C8—N7—C11	110.73 (15)	C42^i—C41—C42	15.9 (8)
N7—C8—C9	106.28 (15)	C41^i—C41—C46	76.4 (2)
N7—C8—O12	124.69 (17)	Cl40—C41—C46	121.2 (4)
C9—C8—O12	129.02 (17)	C45^i—C41—C46	16.2 (4)
C8—C9—C10	108.49 (16)	C44^i—C41—C46	66.9 (5)
C8—C9—C14	129.54 (17)	C42^i—C41—C46	133.2 (6)
C10—C9—C14	121.94 (18)	C43^i—C41—C42	94.5 (8)
C9—C10—C11	107.80 (16)	C43^i—C41—C46	145.1 (8)
C9—C10—C17	122.35 (18)	C42—C41—C46	120.14 (18)
C11—C10—C17	129.84 (17)	H421^i—C42—C43^i	93.4
C10—C11—N7	106.70 (14)	H421^i—C42—C41	124.7
C10—C11—O13	129.09 (17)	C43^i—C42—C41	31.7 (3)
N7—C11—O13	124.21 (17)	H421^i—C42—C41^i	152.5
C9—C14—C15	116.47 (17)	C43^i—C42—C41^i	110.5 (4)
C9—C14—N18	118.11 (16)	C41—C42—C41^i	78.9 (4)
C15—C14—N18	125.40 (17)	H421^i—C42—C43	113.1
C14—C15—C16	120.88 (18)	C43^i—C42—C43	151.3 (4)
C14—C15—H151	120.1	C41—C42—C43	120.03 (18)
C16—C15—H151	119.0	C41^i—C42—C43	41.2 (4)
C15—C16—C17	122.34 (18)	H421^i—C42—H421	5.8
C15—C16—H161	118.9	C43^i—C42—H421	87.7
C17—C16—H161	118.8	C41—C42—H421	119.1
C16—C17—C10	116.01 (18)	C41^i—C42—H421	157.8
C16—C17—H171	121.6	C43—C42—H421	118.8
C10—C17—H171	122.4	C42^i—C43—C42	8.4 (10)
C14—N18—C19	128.21 (17)	C42^i—C43—C41^i	53.7 (6)
C14—N18—H181	115.9	C42—C43—C41^i	57.2 (5)
C19—N18—H181	115.9	C42^i—C43—C44	117.1 (2)
N18—C19—C20	113.96 (17)	C42—C43—C44	120.04 (18)
N18—C19—O21	123.53 (18)	C41^i—C43—C44	63.4 (5)
C20—C19—O21	122.51 (18)	C42^i—C43—H431	124.0
C19—C20—H201	108.7	C42—C43—H431	120.6
C19—C20—H202	106.4	C41^i—C43—H431	177.7
H201—C20—H202	112.1	C44—C43—H431	118.9
C19—C20—H203	110.2	C46^i—C44—C43	98.1 (2)
H201—C20—H203	107.3	C46^i—C44—C41^i	59.8 (4)
H202—C20—H203	112.2	C43—C44—C41^i	38.4 (3)
C6—C22—C23	122.22 (17)	C46^i—C44—Cl40^i	135.8 (4)
C6—C22—C27	118.49 (17)	C43—C44—Cl40^i	38.2 (3)
C23—C22—C27	119.28 (18)	C41^i—C44—Cl40^i	76.5 (4)
C22—C23—C24	120.50 (17)	C46^i—C44—C45	22.1 (2)
C22—C23—H231	119.2	C43—C44—C45	119.90 (17)
C24—C23—H231	120.3	C41^i—C44—C45	81.6 (3)
C23—C24—C25	119.77 (17)	Cl40^i—C44—C45	157.9 (3)
C23—C24—O28	124.78 (17)	C46^i—C44—H441	141.3
C25—C24—O28	115.44 (17)	C43—C44—H441	120.5
C24—C25—C26	119.45 (17)	C41^i—C44—H441	158.8
C24—C25—O31	115.97 (16)	Cl40^i—C44—H441	82.3
C26—C25—O31	124.58 (17)	C45—C44—H441	119.6
C25—C26—C27	120.11 (17)	C44—C45—C41^i	47.4 (3)
C25—C26—H261	119.9	C44—C45—C45^i	135.0 (2)
C27—C26—H261	120.0	C41^i—C45—C45^i	87.7 (3)
C26—C27—C22	120.88 (18)	C44—C45—C46	119.42 (17)
C26—C27—H271	121.0	C41^i—C45—C46	72.1 (3)
C22—C27—H271	118.1	C45^i—C45—C46	16.3 (3)
C24—O28—C29	116.94 (15)	C44—C45—H451	120.4
O28—C29—C30	107.88 (18)	C41^i—C45—H451	167.7
O28—C29—H291	109.1	C45^i—C45—H451	104.4
C30—C29—H291	108.3	C46—C45—H451	120.2
O28—C29—H292	110.3	C44^i—C46—C45	172.1 (5)
C30—C29—H292	111.5	C44^i—C46—C41	53.3 (4)
H291—C29—H292	109.6	C45—C46—C41	119.47 (17)
C29—C30—H301	110.7	C44^i—C46—C46^i	154.9 (6)
C29—C30—H302	111.7	C45—C46—C46^i	17.2 (5)
H301—C30—H302	108.4	C41—C46—C46^i	103.3 (3)
C29—C30—H303	111.7	C44^i—C46—H461	66.9
H301—C30—H303	104.6	C45—C46—H461	120.4
H302—C30—H303	109.5	C41—C46—H461	120.1
C25—O31—C32	116.22 (16)	C46^i—C46—H461	136.0
O31—C32—H321	107.5	C42—H421—C42^i	25.6
O31—C32—H322	110.7	C43—H431—Cl40^i	62.3
H321—C32—H322	108.1	C44—H441—Cl40^i	60.6
O31—C32—H323	110.3	H461^i—H451—C45	22.7
H321—C32—H323	109.8	H451^i—H461—C46	127.1

Symmetry code: (i) −y+1, −x+1, −z+3/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H41···O12^ii	1.00	2.40	3.056 (4)	122
C4—H43···O2^iii	1.00	2.46	3.350 (4)	149
C5—H51···O21^iv	0.97	2.45	3.410 (4)	167
C5—H52···O13^iii	0.96	2.33	3.156 (4)	145
C15—H151···O21	0.92	2.32	2.901 (4)	121
N18—H181···O12	0.95	2.22	2.963 (4)	134
C23—H231···O13^iii	0.95	2.44	3.387 (4)	178
C26—H261···O3^iv	0.92	2.44	3.339 (4)	165
C27—H271···O2^iv	0.95	2.52	3.267 (4)	135
C45—H451···O2^v	0.95	2.60	3.543 (4)	173

Symmetry codes: (ii) y+1/2, −x+3/2, z−1/4; (iii) y, x, −z+1; (iv) −x+3/2, y−1/2, −z+5/4; (v) −y+3/2, x−1/2, z+1/4.

(ApreHexa)

Crystal data

2(C22H24N2O7S)·(C6F6)	Dx = 1.514 Mg m^−3
Mr = 1107.1	Cu Kα radiation, λ = 1.54184 Å
Tetragonal, P41212	Cell parameters from 32712 reflections
Hall symbol: P 43n;2nw	θ = 3.0–74.0°
a = 12.8425 (1) Å	µ = 1.84 mm^−1
c = 29.4534 (2) Å	T = 120 K
V = 4857.74 (6) Å^3	Block, yellow
Z = 4	0.34 × 0.25 × 0.17 mm
F(000) = 2296

Data collection

SuperNova, Dual, Cu at home/near, AtlasS2 diffractometer	4928 independent reflections
Radiation source: X-ray tube	4897 reflections with I > 3σ(I)
Mirror monochromator	Rint = 0.018
Detector resolution: 5.2027 pixels mm^-1	θmax = 74.3°, θmin = 3.8°
ω scans	h = −15→15
Absorption correction: analytical CrysAlisPro 1.171.40.67a (Rigaku Oxford Diffraction, 2019) Analytical numeric absorption correction based on crystal shape	k = −15→15
Tmin = 0.671, Tmax = 0.796	l = −36→36
41296 measured reflections

Refinement

Refinement on F^2	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.023	Weighting scheme based on measured s.u.'s w = 1/(σ^2(I) + 0.0016I^2)
wR(F^2) = 0.072	(Δ/σ)max = 0.021
S = 1.66	Δρmax = 0.16 e Å^−3
4928 reflections	Δρmin = −0.21 e Å^−3
349 parameters	Absolute structure: 2035 of Friedel pairs used in the refinement
1 restraint	Absolute structure parameter: 0.004 (9)
93 constraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.16716 (2)	0.59424 (2)	0.712495 (8)	0.01827 (7)
F1	0.79300 (9)	0.20700 (9)	0.75	0.0599 (4)
F2	0.91597 (10)	0.18083 (8)	0.82396 (3)	0.0541 (3)
F3	1.06368 (9)	0.03077 (9)	0.82434 (4)	0.0554 (3)
F4	1.09175 (9)	−0.09175 (9)	0.75	0.0610 (4)
O1	0.47431 (6)	0.59043 (7)	0.69488 (3)	0.0212 (2)
O2	0.23649 (7)	0.51093 (6)	0.58451 (3)	0.0202 (2)
O3	0.21769 (7)	0.68444 (7)	0.69299 (3)	0.0252 (2)
O4	0.07948 (7)	0.55094 (7)	0.68841 (3)	0.0269 (2)
O5	0.54631 (7)	0.23422 (6)	0.76843 (3)	0.0202 (2)
O6	0.55846 (7)	0.09487 (7)	0.70395 (3)	0.0223 (2)
O7	0.31494 (7)	0.78740 (7)	0.45864 (3)	0.0275 (2)
N1	0.34699 (7)	0.52852 (7)	0.64649 (3)	0.0155 (2)
N2	0.28903 (7)	0.66880 (7)	0.51529 (3)	0.0185 (2)
C1	0.42738 (8)	0.59541 (9)	0.65931 (3)	0.0162 (3)
C2	0.30732 (8)	0.55534 (8)	0.60383 (3)	0.0158 (3)
C3	0.36833 (8)	0.64609 (8)	0.58815 (4)	0.0159 (3)
C4	0.36203 (8)	0.70139 (8)	0.54747 (4)	0.0164 (3)
C5	0.43298 (9)	0.78404 (9)	0.54194 (4)	0.0200 (3)
C6	0.50511 (9)	0.80799 (9)	0.57592 (4)	0.0223 (3)
C7	0.51127 (9)	0.75145 (9)	0.61652 (4)	0.0213 (3)
C8	0.44134 (8)	0.67054 (9)	0.62133 (3)	0.0172 (3)
C9	0.29946 (8)	0.44849 (8)	0.67568 (3)	0.0161 (3)
C10	0.26178 (8)	0.49535 (8)	0.72064 (3)	0.0173 (3)
C11	0.12892 (11)	0.62580 (11)	0.76816 (4)	0.0293 (3)
C12	0.37136 (8)	0.35585 (9)	0.68342 (4)	0.0169 (3)
C13	0.42630 (8)	0.34120 (8)	0.72406 (3)	0.0177 (3)
C14	0.48941 (8)	0.25425 (8)	0.73014 (4)	0.0171 (3)
C15	0.49734 (9)	0.17951 (8)	0.69495 (4)	0.0176 (3)
C16	0.44369 (9)	0.19507 (9)	0.65468 (4)	0.0195 (3)
C17	0.38102 (9)	0.28280 (9)	0.64905 (4)	0.0189 (3)
C18	0.54743 (9)	0.31501 (9)	0.80237 (4)	0.0210 (3)
C19	0.62629 (11)	0.28555 (11)	0.83813 (4)	0.0305 (4)
C20	0.57506 (10)	0.02516 (9)	0.66685 (4)	0.0246 (3)
C21	0.27073 (9)	0.71040 (9)	0.47284 (3)	0.0195 (3)
C22	0.19379 (9)	0.64936 (10)	0.44499 (4)	0.0241 (3)
C23	0.86636 (12)	0.13364 (12)	0.75	0.0356 (4)
C24	0.92905 (13)	0.12041 (11)	0.78747 (5)	0.0365 (4)
C25	1.00426 (12)	0.04442 (12)	0.78760 (5)	0.0369 (4)
C26	1.01845 (12)	−0.01845 (12)	0.75	0.0376 (5)
H1c5	0.4318	0.824406	0.514512	0.024*
H1c6	0.552059	0.865173	0.571281	0.0268*
H1c7	0.561243	0.768011	0.639659	0.0256*
H1c9	0.239689	0.422257	0.659799	0.0193*
H1c10	0.320103	0.523418	0.736951	0.0208*
H2c10	0.233166	0.441284	0.739374	0.0208*
H1c11	0.099735	0.565369	0.782518	0.0352*
H2c11	0.188437	0.649024	0.785086	0.0352*
H3c11	0.077727	0.680229	0.767265	0.0352*
H1c13	0.420322	0.391711	0.74794	0.0212*
H1c16	0.449706	0.145203	0.630543	0.0235*
H1c17	0.344125	0.292695	0.621035	0.0226*
H1c18	0.479754	0.320397	0.816009	0.0252*
H2c18	0.567339	0.379762	0.788591	0.0252*
H1c19	0.630144	0.339663	0.860556	0.0366*
H2c19	0.605567	0.221577	0.852369	0.0366*
H3c19	0.693301	0.276675	0.82422	0.0366*
H1c20	0.61677	−0.032525	0.676802	0.0295*
H2c20	0.509186	−0.000005	0.656033	0.0295*
H3c20	0.610371	0.061151	0.64279	0.0295*
H1c22	0.138627	0.624901	0.464229	0.0289*
H2c22	0.165366	0.693263	0.421702	0.0289*
H3c22	0.22828	0.590984	0.431273	0.0289*
H1n2	0.2529 (11)	0.6157 (8)	0.5235 (5)	0.0223*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.01925 (13)	0.02004 (13)	0.01552 (12)	0.00511 (9)	0.00156 (9)	0.00123 (9)
F1	0.0539 (6)	0.0539 (6)	0.0718 (10)	0.0121 (7)	0.0118 (6)	0.0118 (6)
F2	0.0792 (7)	0.0442 (5)	0.0390 (5)	−0.0212 (5)	0.0123 (5)	−0.0116 (4)
F3	0.0563 (6)	0.0652 (7)	0.0447 (5)	−0.0225 (5)	−0.0178 (5)	0.0206 (5)
F4	0.0488 (5)	0.0488 (5)	0.0855 (11)	0.0076 (7)	0.0127 (6)	0.0127 (6)
O1	0.0200 (4)	0.0278 (4)	0.0159 (3)	0.0019 (3)	−0.0047 (3)	−0.0024 (3)
O2	0.0231 (4)	0.0210 (4)	0.0164 (3)	−0.0044 (3)	−0.0048 (3)	−0.0003 (3)
O3	0.0301 (4)	0.0211 (4)	0.0243 (4)	0.0045 (3)	0.0044 (3)	0.0048 (3)
O4	0.0225 (4)	0.0312 (4)	0.0269 (4)	0.0044 (3)	−0.0049 (3)	0.0010 (3)
O5	0.0245 (4)	0.0185 (4)	0.0177 (3)	0.0049 (3)	−0.0067 (3)	−0.0034 (3)
O6	0.0277 (4)	0.0186 (4)	0.0205 (3)	0.0072 (3)	−0.0016 (3)	−0.0031 (3)
O7	0.0311 (4)	0.0311 (5)	0.0202 (4)	−0.0089 (4)	−0.0026 (3)	0.0061 (3)
N1	0.0162 (4)	0.0181 (4)	0.0121 (4)	0.0006 (3)	−0.0018 (3)	−0.0008 (3)
N2	0.0210 (5)	0.0186 (4)	0.0160 (4)	−0.0029 (3)	−0.0031 (3)	0.0007 (3)
C1	0.0144 (4)	0.0190 (5)	0.0153 (4)	0.0024 (4)	−0.0001 (4)	−0.0040 (4)
C2	0.0177 (5)	0.0169 (5)	0.0129 (4)	0.0034 (4)	−0.0008 (4)	−0.0010 (3)
C3	0.0159 (5)	0.0160 (5)	0.0156 (5)	0.0018 (4)	0.0011 (3)	−0.0024 (4)
C4	0.0167 (5)	0.0171 (5)	0.0154 (5)	0.0013 (4)	0.0003 (4)	−0.0017 (4)
C5	0.0185 (5)	0.0201 (5)	0.0213 (5)	0.0004 (4)	−0.0012 (4)	0.0019 (4)
C6	0.0204 (5)	0.0201 (5)	0.0264 (5)	−0.0031 (4)	−0.0015 (4)	0.0006 (4)
C7	0.0184 (5)	0.0229 (5)	0.0227 (5)	−0.0006 (4)	−0.0029 (4)	−0.0024 (4)
C8	0.0170 (5)	0.0183 (5)	0.0163 (4)	0.0029 (4)	−0.0005 (4)	−0.0029 (4)
C9	0.0175 (5)	0.0174 (5)	0.0134 (4)	0.0004 (4)	−0.0009 (3)	−0.0002 (4)
C10	0.0186 (5)	0.0194 (5)	0.0140 (4)	0.0044 (4)	0.0001 (4)	0.0010 (4)
C11	0.0319 (6)	0.0343 (7)	0.0219 (5)	0.0058 (5)	0.0093 (5)	−0.0029 (5)
C12	0.0172 (5)	0.0171 (5)	0.0165 (5)	0.0006 (4)	0.0000 (4)	0.0000 (4)
C13	0.0194 (5)	0.0178 (5)	0.0158 (5)	0.0007 (4)	−0.0013 (4)	−0.0026 (4)
C14	0.0189 (5)	0.0177 (5)	0.0148 (4)	−0.0012 (4)	−0.0016 (4)	−0.0001 (4)
C15	0.0190 (5)	0.0151 (4)	0.0186 (5)	0.0002 (4)	0.0016 (4)	−0.0014 (4)
C16	0.0219 (5)	0.0193 (5)	0.0175 (5)	−0.0012 (4)	0.0000 (4)	−0.0042 (4)
C17	0.0215 (5)	0.0202 (5)	0.0149 (4)	0.0004 (4)	−0.0022 (4)	−0.0023 (4)
C18	0.0278 (6)	0.0173 (5)	0.0181 (4)	0.0028 (4)	−0.0045 (4)	−0.0029 (4)
C19	0.0388 (7)	0.0310 (6)	0.0217 (5)	0.0090 (5)	−0.0123 (5)	−0.0061 (5)
C20	0.0329 (6)	0.0184 (5)	0.0225 (5)	0.0069 (5)	0.0039 (4)	−0.0034 (4)
C21	0.0198 (5)	0.0233 (5)	0.0154 (4)	0.0009 (4)	−0.0004 (4)	0.0005 (4)
C22	0.0266 (6)	0.0291 (6)	0.0164 (5)	−0.0041 (5)	−0.0046 (4)	−0.0014 (4)
C23	0.0339 (6)	0.0339 (6)	0.0390 (10)	−0.0055 (8)	0.0067 (5)	0.0067 (5)
C24	0.0448 (8)	0.0336 (7)	0.0310 (6)	−0.0168 (6)	0.0074 (6)	−0.0019 (5)
C25	0.0374 (7)	0.0421 (7)	0.0314 (6)	−0.0195 (6)	−0.0039 (6)	0.0125 (6)
C26	0.0317 (6)	0.0317 (6)	0.0494 (11)	−0.0071 (8)	0.0088 (6)	0.0088 (6)

Geometric parameters (Å, º)

S1—O3	1.4467 (9)	C9—C12	1.5232 (15)
S1—O4	1.4423 (9)	C9—H1c9	0.96
S1—C10	1.7740 (11)	C10—H1c10	0.96
S1—C11	1.7589 (13)	C10—H2c10	0.96
F1—C23	1.3323 (19)	C11—H1c11	0.96
F2—C24	1.3362 (17)	C11—H2c11	0.96
F3—C25	1.3356 (18)	C11—H3c11	0.96
F4—C26	1.3314 (19)	C12—C13	1.4021 (15)
O1—C1	1.2103 (13)	C12—C17	1.3857 (15)
O2—C2	1.2151 (13)	C13—C14	1.3914 (15)
O5—C14	1.3682 (13)	C13—H1c13	0.96
O5—C18	1.4406 (13)	C14—C15	1.4165 (15)
O6—C15	1.3668 (14)	C15—C16	1.3861 (15)
O6—C20	1.4285 (14)	C16—C17	1.3944 (16)
O7—C21	1.2146 (15)	C16—H1c16	0.96
N1—C1	1.3952 (14)	C17—H1c17	0.96
N1—C2	1.3987 (13)	C18—C19	1.5095 (17)
N1—C9	1.4724 (13)	C18—H1c18	0.96
N2—C4	1.3971 (14)	C18—H2c18	0.96
N2—C21	1.3799 (14)	C19—H1c19	0.96
N2—H1n2	0.859 (12)	C19—H2c19	0.96
C1—C8	1.4881 (15)	C19—H3c19	0.96
C2—C3	1.4783 (15)	C20—H1c20	0.96
C3—C4	1.3953 (15)	C20—H2c20	0.96
C3—C8	1.3901 (15)	C20—H3c20	0.96
C4—C5	1.4083 (15)	C21—C22	1.5045 (16)
C5—C6	1.3981 (16)	C22—H1c22	0.96
C5—H1c5	0.96	C22—H2c22	0.96
C6—C7	1.4011 (17)	C22—H3c22	0.96
C6—H1c6	0.96	C23—C24	1.3766 (18)
C7—C8	1.3807 (16)	C23—C24^i	1.3766 (18)
C7—H1c7	0.96	C24—C25	1.373 (2)
C9—C10	1.5330 (14)	C25—C26	1.3826 (17)
O3—S1—O4	117.62 (5)	C9—C12—C17	118.28 (9)
O3—S1—C10	108.64 (5)	C13—C12—C17	119.19 (10)
O3—S1—C11	108.11 (6)	C12—C13—C14	120.72 (9)
O4—S1—C10	108.98 (5)	C12—C13—H1c13	119.64
O4—S1—C11	109.22 (6)	C14—C13—H1c13	119.64
C10—S1—C11	103.30 (6)	O5—C14—C13	124.62 (9)
C14—O5—C18	116.22 (8)	O5—C14—C15	115.94 (9)
C15—O6—C20	115.84 (9)	C13—C14—C15	119.43 (9)
C1—N1—C2	111.16 (9)	O6—C15—C14	116.00 (9)
C1—N1—C9	125.34 (8)	O6—C15—C16	124.48 (10)
C2—N1—C9	123.05 (9)	C14—C15—C16	119.52 (10)
C4—N2—C21	127.80 (9)	C15—C16—C17	120.34 (10)
C4—N2—H1n2	114.2 (10)	C15—C16—H1c16	119.83
C21—N2—H1n2	118.0 (10)	C17—C16—H1c16	119.83
O1—C1—N1	124.76 (10)	C12—C17—C16	120.78 (10)
O1—C1—C8	128.68 (10)	C12—C17—H1c17	119.61
N1—C1—C8	106.55 (8)	C16—C17—H1c17	119.61
O2—C2—N1	125.29 (10)	O5—C18—C19	108.08 (9)
O2—C2—C3	128.35 (9)	O5—C18—H1c18	109.47
N1—C2—C3	106.36 (9)	O5—C18—H2c18	109.47
C2—C3—C4	129.70 (10)	C19—C18—H1c18	109.47
C2—C3—C8	108.42 (9)	C19—C18—H2c18	109.47
C4—C3—C8	121.86 (10)	H1c18—C18—H2c18	110.83
N2—C4—C3	117.97 (9)	C18—C19—H1c19	109.47
N2—C4—C5	125.56 (10)	C18—C19—H2c19	109.47
C3—C4—C5	116.44 (10)	C18—C19—H3c19	109.47
C4—C5—C6	120.78 (10)	H1c19—C19—H2c19	109.47
C4—C5—H1c5	119.61	H1c19—C19—H3c19	109.47
C6—C5—H1c5	119.61	H2c19—C19—H3c19	109.47
C5—C6—C7	122.30 (11)	O6—C20—H1c20	109.47
C5—C6—H1c6	118.85	O6—C20—H2c20	109.47
C7—C6—H1c6	118.85	O6—C20—H3c20	109.47
C6—C7—C8	116.15 (10)	H1c20—C20—H2c20	109.47
C6—C7—H1c7	121.92	H1c20—C20—H3c20	109.47
C8—C7—H1c7	121.92	H2c20—C20—H3c20	109.47
C1—C8—C3	107.50 (9)	O7—C21—N2	123.19 (10)
C1—C8—C7	130.04 (10)	O7—C21—C22	122.92 (10)
C3—C8—C7	122.46 (10)	N2—C21—C22	113.85 (10)
N1—C9—C10	111.18 (8)	C21—C22—H1c22	109.47
N1—C9—C12	112.42 (8)	C21—C22—H2c22	109.47
N1—C9—H1c9	106.97	C21—C22—H3c22	109.47
C10—C9—C12	111.63 (8)	H1c22—C22—H2c22	109.47
C10—C9—H1c9	107.83	H1c22—C22—H3c22	109.47
C12—C9—H1c9	106.47	H2c22—C22—H3c22	109.47
S1—C10—C9	112.36 (7)	F1—C23—C24	120.05 (9)
S1—C10—H1c10	109.47	F1—C23—C24^i	120.05 (9)
S1—C10—H2c10	109.47	C24—C23—C24^i	119.90 (14)
C9—C10—H1c10	109.47	F2—C24—C23	119.98 (14)
C9—C10—H2c10	109.47	F2—C24—C25	119.93 (13)
H1c10—C10—H2c10	106.42	C23—C24—C25	120.08 (13)
S1—C11—H1c11	109.47	F3—C25—C24	119.83 (13)
S1—C11—H2c11	109.47	F3—C25—C26	119.80 (14)
S1—C11—H3c11	109.47	C24—C25—C26	120.37 (13)
H1c11—C11—H2c11	109.47	F4—C26—C25	120.41 (9)
H1c11—C11—H3c11	109.47	F4—C26—C25^i	120.41 (9)
H2c11—C11—H3c11	109.47	C25—C26—C25^i	119.19 (14)
C9—C12—C13	122.53 (9)

Symmetry code: (i) −y+1, −x+1, −z+3/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H1c5···O7	0.96	2.28	2.8842 (14)	120
C10—H1c10···O1	0.96	2.49	3.0848 (13)	120
C10—H1c10···O1^i	0.96	2.31	3.1537 (13)	146
C11—H2c11···O3^i	0.96	2.45	3.3308 (16)	152
C11—H3c11···O2^ii	0.96	2.40	3.0109 (15)	121
C13—H1c13···O1^i	0.96	2.41	3.3707 (13)	177
C16—H1c16···O4^iii	0.96	2.39	3.3216 (14)	162
C17—H1c17···O3^iii	0.96	2.47	3.2484 (14)	138
C20—H1c20···O7^iv	0.96	2.50	3.4531 (15)	174
N2—H1n2···O2	0.859 (12)	2.256 (13)	2.9534 (12)	138.3 (12)

Symmetry codes: (i) −y+1, −x+1, −z+3/2; (ii) −y+1/2, x+1/2, z+1/4; (iii) −x+1/2, y−1/2, −z+5/4; (iv) −y+3/2, x−1/2, z+1/4.

(apremilastiodobenzene)

Crystal data

2(C22H24N2O7S)·C6H5I	Dx = 1.522 Mg m^−3
Mr = 1124.98	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 56749 reflections
a = 12.9104 (1) Å	θ = 5–76°
c = 29.4495 (1) Å	µ = 6.53 mm^−1
V = 4908.60 (8) Å^3	T = 95 K
Z = 4	Block, colorless
F(000) = 2312	0.19 × 0.14 × 0.12 mm

Data collection

Oxford Diffraction SuperNova diffractometer	5108 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.030
ω scans	θmax = 76.3°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −16→15
Tmin = 0.15, Tmax = 0.45	k = −15→16
86093 measured reflections	l = −37→37
5141 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.036	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.02P)^2 + 11.85P] , where P = (max(Fo^2,0) + 2Fc^2)/3
wR(F^2) = 0.079	(Δ/σ)max = 0.004
S = 1.00	Δρmax = 0.99 e Å^−3
5141 reflections	Δρmin = −1.74 e Å^−3
329 parameters	Absolute structure: Flack (1983), 2129 Friedel-pairs
16 restraints	Absolute structure parameter: −0.004 (4)
Primary atom site location: structure-invariant direct methods

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.39991 (5)	0.84164 (5)	0.28493 (2)	0.0143
O2	0.44130 (15)	0.92927 (16)	0.30926 (7)	0.0214
O3	0.30587 (16)	0.79458 (16)	0.30199 (7)	0.0202
C4	0.3803 (2)	0.8766 (2)	0.22785 (9)	0.0234
C5	0.4967 (2)	0.7453 (2)	0.28021 (8)	0.0139
C6	0.5391 (2)	0.7068 (2)	0.32565 (8)	0.0132
N7	0.45657 (17)	0.66017 (17)	0.35374 (7)	0.0131
C8	0.4274 (2)	0.6977 (2)	0.39633 (8)	0.0128
C9	0.3398 (2)	0.63273 (19)	0.41141 (8)	0.0128
C10	0.3175 (2)	0.5609 (2)	0.37752 (8)	0.0132
C11	0.39286 (19)	0.5786 (2)	0.34004 (9)	0.0146
O12	0.46803 (15)	0.77031 (15)	0.41582 (6)	0.0156
O13	0.40048 (16)	0.53258 (14)	0.30421 (6)	0.0173
C14	0.2845 (2)	0.6340 (2)	0.45217 (9)	0.0141
C15	0.2044 (2)	0.5611 (2)	0.45675 (9)	0.0184
C16	0.1827 (2)	0.4918 (2)	0.42203 (10)	0.0191
C17	0.2391 (2)	0.4895 (2)	0.38147 (9)	0.0172
N18	0.31505 (18)	0.70543 (17)	0.48536 (7)	0.0153
C19	0.2742 (2)	0.7204 (2)	0.52796 (9)	0.0160
C20	0.3364 (2)	0.7932 (2)	0.55661 (9)	0.0210
O21	0.19585 (16)	0.67727 (16)	0.54135 (6)	0.0218
C22	0.6302 (2)	0.6344 (2)	0.31915 (9)	0.0137
C23	0.6470 (2)	0.5810 (2)	0.27820 (9)	0.0154
C24	0.7324 (2)	0.5168 (2)	0.27287 (9)	0.0146
C25	0.8041 (2)	0.5061 (2)	0.30869 (9)	0.0155
C26	0.7867 (2)	0.5582 (2)	0.34922 (9)	0.0156
C27	0.7007 (2)	0.6221 (2)	0.35420 (9)	0.0151
O28	0.75315 (15)	0.46153 (15)	0.23414 (6)	0.0175
C29	0.6766 (2)	0.4665 (2)	0.19891 (9)	0.0180
C30	0.7078 (2)	0.3935 (3)	0.16140 (10)	0.0251
O31	0.88757 (15)	0.44391 (15)	0.30014 (6)	0.0195
C32	0.9598 (2)	0.4324 (2)	0.33649 (10)	0.0211
I33	0.582336 (19)	0.582336 (19)	0.5000	0.0824
C34	0.4679 (2)	0.4679 (2)	0.5000	0.0274
C35	0.4601 (3)	0.4024 (3)	0.46354 (11)	0.0356
C36	0.3834 (3)	0.3224 (3)	0.46390 (13)	0.0385
C37	0.3180 (3)	0.3180 (3)	0.500000 (7)	0.0506
H51	0.5530	0.7761	0.2633	0.0181*
H52	0.4683	0.6872	0.2639	0.0182*
H61	0.5643	0.7670	0.3424	0.0171*
H151	0.1654	0.5591	0.4833	0.0229*
H161	0.1285	0.4449	0.4258	0.0231*
H171	0.2250	0.4427	0.3583	0.0211*
H201	0.2987	0.8086	0.5837	0.0312*
H203	0.4010	0.7613	0.5650	0.0312*
H202	0.3507	0.8567	0.5407	0.0310*
H231	0.5998	0.5883	0.2543	0.0190*
H261	0.8333	0.5504	0.3730	0.0192*
H271	0.6898	0.6569	0.3815	0.0191*
H291	0.6729	0.5372	0.1867	0.0221*
H292	0.6091	0.4470	0.2105	0.0220*
H302	0.6543	0.3918	0.1389	0.0392*
H301	0.7714	0.4171	0.1479	0.0392*
H303	0.7177	0.3250	0.1734	0.0389*
H322	1.0145	0.3876	0.3265	0.0322*
H321	0.9886	0.4987	0.3447	0.0320*
H323	0.9257	0.4022	0.3623	0.0322*
H351	0.5036	0.4113	0.4382	0.0421*
H361	0.3794	0.2750	0.4407	0.0463*
H371	0.2671	0.2671	0.5000	0.0603*
H43	0.3292	0.9301	0.2261	0.0379*
H181	0.3667 (19)	0.742 (2)	0.4785 (7)	0.018 (2)*
H42	0.3564	0.8178	0.2107	0.0378*
H41	0.4448	0.9013	0.2150	0.0379*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0136 (3)	0.0153 (3)	0.0139 (3)	0.0036 (2)	0.0021 (2)	0.0016 (2)
O2	0.0225 (10)	0.0171 (10)	0.0247 (10)	0.0039 (8)	0.0029 (8)	−0.0032 (8)
O3	0.0168 (10)	0.0234 (10)	0.0204 (9)	0.0020 (8)	0.0043 (8)	0.0026 (8)
C4	0.0223 (15)	0.0288 (16)	0.0192 (13)	0.0061 (12)	0.0008 (11)	0.0090 (12)
C5	0.0147 (12)	0.0144 (12)	0.0126 (11)	0.0049 (10)	0.0023 (10)	0.0000 (10)
C6	0.0155 (13)	0.0146 (12)	0.0095 (11)	0.0011 (10)	0.0000 (9)	0.0000 (9)
N7	0.0158 (11)	0.0135 (10)	0.0102 (9)	0.0009 (9)	−0.0014 (8)	−0.0029 (8)
C8	0.0128 (12)	0.0141 (12)	0.0115 (11)	0.0039 (10)	−0.0009 (9)	0.0016 (9)
C9	0.0144 (12)	0.0111 (12)	0.0128 (11)	0.0021 (10)	−0.0028 (10)	0.0012 (9)
C10	0.0148 (12)	0.0124 (12)	0.0123 (11)	0.0035 (9)	−0.0030 (10)	−0.0004 (9)
C11	0.0153 (12)	0.0122 (12)	0.0163 (12)	0.0033 (10)	−0.0018 (10)	0.0016 (10)
O12	0.0183 (10)	0.0150 (9)	0.0133 (8)	−0.0016 (7)	−0.0023 (7)	−0.0037 (7)
O13	0.0232 (10)	0.0162 (9)	0.0124 (8)	0.0018 (8)	−0.0017 (8)	−0.0051 (7)
C14	0.0146 (12)	0.0130 (12)	0.0145 (12)	0.0018 (10)	−0.0030 (10)	0.0000 (10)
C15	0.0169 (13)	0.0226 (14)	0.0157 (12)	0.0009 (11)	0.0013 (10)	0.0001 (11)
C16	0.0161 (13)	0.0159 (13)	0.0253 (14)	−0.0028 (11)	−0.0015 (11)	0.0001 (11)
C17	0.0186 (13)	0.0147 (13)	0.0185 (13)	0.0003 (11)	−0.0043 (11)	−0.0037 (10)
N18	0.0154 (11)	0.0158 (11)	0.0149 (10)	−0.0021 (9)	0.0014 (9)	−0.0024 (9)
C19	0.0178 (14)	0.0174 (13)	0.0129 (12)	0.0044 (10)	−0.0002 (10)	0.0010 (10)
C20	0.0240 (15)	0.0246 (15)	0.0145 (12)	−0.0016 (12)	0.0000 (11)	−0.0031 (11)
O21	0.0222 (10)	0.0258 (11)	0.0174 (9)	−0.0043 (9)	0.0053 (8)	−0.0016 (8)
C22	0.0134 (12)	0.0141 (12)	0.0138 (12)	0.0002 (9)	0.0009 (10)	0.0006 (9)
C23	0.0142 (12)	0.0151 (12)	0.0170 (12)	0.0021 (10)	−0.0036 (10)	−0.0020 (10)
C24	0.0157 (13)	0.0128 (12)	0.0154 (11)	−0.0006 (10)	0.0011 (10)	−0.0019 (10)
C25	0.0119 (12)	0.0135 (12)	0.0211 (13)	0.0012 (10)	−0.0009 (10)	0.0011 (10)
C26	0.0135 (12)	0.0166 (13)	0.0168 (12)	−0.0010 (10)	−0.0058 (10)	0.0027 (10)
C27	0.0165 (13)	0.0170 (13)	0.0119 (12)	−0.0009 (10)	−0.0003 (10)	−0.0017 (10)
O28	0.0164 (9)	0.0216 (10)	0.0145 (9)	0.0060 (7)	−0.0035 (7)	−0.0066 (8)
C29	0.0164 (13)	0.0228 (14)	0.0148 (12)	0.0023 (11)	−0.0010 (10)	−0.0032 (11)
C30	0.0268 (15)	0.0302 (17)	0.0184 (13)	0.0063 (13)	−0.0041 (12)	−0.0073 (12)
O31	0.0162 (9)	0.0227 (10)	0.0195 (9)	0.0066 (8)	−0.0036 (8)	−0.0019 (8)
C32	0.0131 (13)	0.0297 (16)	0.0203 (13)	0.0067 (12)	−0.0020 (11)	0.0050 (12)
I33	0.03570 (14)	0.03570 (14)	0.1759 (6)	−0.01778 (17)	−0.0541 (2)	0.0541 (2)
C34	0.0191 (12)	0.0191 (12)	0.044 (3)	−0.0018 (16)	−0.0109 (14)	0.0109 (14)
C35	0.0350 (18)	0.046 (2)	0.0254 (16)	0.0116 (17)	0.0016 (14)	0.0091 (16)
C36	0.045 (2)	0.0324 (18)	0.0381 (19)	0.0001 (15)	−0.0276 (17)	−0.0018 (15)
C37	0.0388 (19)	0.0388 (19)	0.074 (4)	−0.023 (2)	−0.035 (2)	0.035 (2)

Geometric parameters (Å, º)

S1—O2	1.442 (2)	C20—H201	0.956
S1—O3	1.448 (2)	C20—H203	0.962
S1—C4	1.759 (3)	C20—H202	0.961
S1—C5	1.769 (3)	C22—C23	1.406 (4)
C4—H43	0.957	C22—C27	1.385 (4)
C4—H42	0.963	C23—C24	1.388 (4)
C4—H41	0.969	C23—H231	0.937
C5—C6	1.529 (3)	C24—C25	1.410 (4)
C5—H51	0.966	C24—O28	1.371 (3)
C5—H52	0.964	C25—C26	1.388 (4)
C6—N7	1.477 (3)	C25—O31	1.368 (3)
C6—C22	1.515 (4)	C26—C27	1.392 (4)
C6—H61	0.975	C26—H261	0.929
N7—C8	1.396 (3)	C27—H271	0.931
N7—C11	1.396 (3)	O28—C29	1.434 (3)
C8—C9	1.477 (4)	C29—C30	1.507 (4)
C8—O12	1.217 (3)	C29—H291	0.983
C9—C10	1.393 (3)	C29—H292	0.970
C9—C14	1.397 (4)	C30—H302	0.957
C10—C11	1.489 (4)	C30—H301	0.962
C10—C17	1.373 (4)	C30—H303	0.960
C11—O13	1.215 (3)	O31—C32	1.428 (3)
C14—C15	1.404 (4)	C32—H322	0.958
C14—N18	1.401 (3)	C32—H321	0.964
C15—C16	1.387 (4)	C32—H323	0.961
C15—H151	0.930	I33—C34	2.089 (4)
C16—C17	1.399 (4)	C34—C35^i	1.371 (4)
C16—H161	0.932	C34—C35	1.371 (4)
C17—H171	0.930	C35—C36	1.430 (5)
N18—C19	1.375 (3)	C35—H351	0.942
N18—H181	0.840 (17)	C36—C37	1.359 (5)
C19—C20	1.498 (4)	C36—H361	0.919
C19—O21	1.220 (3)	C37—H371	0.930
O2—S1—O3	117.88 (12)	C19—C20—H201	109.1
O2—S1—C4	109.10 (14)	C19—C20—H203	109.9
O3—S1—C4	108.58 (14)	H201—C20—H203	108.5
O2—S1—C5	109.21 (12)	C19—C20—H202	111.4
O3—S1—C5	108.95 (13)	H201—C20—H202	109.0
C4—S1—C5	101.93 (13)	H203—C20—H202	108.9
S1—C4—H43	109.7	C6—C22—C23	122.1 (2)
S1—C4—H42	110.3	C6—C22—C27	119.1 (2)
H43—C4—H42	108.6	C23—C22—C27	118.8 (2)
S1—C4—H41	109.6	C22—C23—C24	120.8 (2)
H43—C4—H41	109.4	C22—C23—H231	119.7
H42—C4—H41	109.3	C24—C23—H231	119.5
S1—C5—C6	114.35 (17)	C23—C24—C25	119.6 (2)
S1—C5—H51	106.4	C23—C24—O28	124.0 (2)
C6—C5—H51	108.4	C25—C24—O28	116.4 (2)
S1—C5—H52	108.5	C24—C25—C26	119.4 (2)
C6—C5—H52	108.7	C24—C25—O31	115.9 (2)
H51—C5—H52	110.5	C26—C25—O31	124.8 (2)
C5—C6—N7	111.4 (2)	C25—C26—C27	120.5 (2)
C5—C6—C22	111.6 (2)	C25—C26—H261	119.5
N7—C6—C22	112.3 (2)	C27—C26—H261	120.1
C5—C6—H61	107.6	C26—C27—C22	120.9 (2)
N7—C6—H61	106.4	C26—C27—H271	119.8
C22—C6—H61	107.3	C22—C27—H271	119.3
C6—N7—C8	123.7 (2)	C24—O28—C29	116.4 (2)
C6—N7—C11	124.8 (2)	O28—C29—C30	108.5 (2)
C8—N7—C11	111.3 (2)	O28—C29—H291	109.9
N7—C8—C9	106.2 (2)	C30—C29—H291	109.0
N7—C8—O12	125.1 (2)	O28—C29—H292	110.6
C9—C8—O12	128.7 (2)	C30—C29—H292	109.7
C8—C9—C10	108.8 (2)	H291—C29—H292	109.1
C8—C9—C14	130.1 (2)	C29—C30—H302	109.1
C10—C9—C14	121.2 (2)	C29—C30—H301	109.5
C9—C10—C11	107.1 (2)	H302—C30—H301	109.8
C9—C10—C17	122.6 (2)	C29—C30—H303	110.0
C11—C10—C17	130.3 (2)	H302—C30—H303	109.2
C10—C11—N7	106.7 (2)	H301—C30—H303	109.3
C10—C11—O13	128.4 (2)	C25—O31—C32	116.0 (2)
N7—C11—O13	124.9 (2)	O31—C32—H322	108.3
C9—C14—C15	116.8 (2)	O31—C32—H321	110.4
C9—C14—N18	117.6 (2)	H322—C32—H321	109.2
C15—C14—N18	125.6 (2)	O31—C32—H323	109.7
C14—C15—C16	120.6 (3)	H322—C32—H323	109.6
C14—C15—H151	119.9	H321—C32—H323	109.8
C16—C15—H151	119.5	C35^i—C34—I33	119.3 (2)
C15—C16—C17	122.6 (3)	C35^i—C34—C35	121.5 (4)
C15—C16—H161	118.9	I33—C34—C35	119.3 (2)
C17—C16—H161	118.6	C34—C35—C36	119.4 (3)
C16—C17—C10	116.2 (2)	C34—C35—H351	120.1
C16—C17—H171	122.6	C36—C35—H351	120.4
C10—C17—H171	121.2	C35—C36—C37	117.8 (4)
C14—N18—C19	128.4 (2)	C35—C36—H361	121.0
C14—N18—H181	115.0 (12)	C37—C36—H361	121.2
C19—N18—H181	116.6 (12)	C36^i—C37—C36	124.0 (5)
N18—C19—C20	113.3 (2)	C36^i—C37—H371	118.0
N18—C19—O21	123.3 (3)	C36—C37—H371	118.0
C20—C19—O21	123.3 (2)

Symmetry code: (i) y, x, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H51···O21^ii	0.97	2.52	3.471 (4)	168
C5—H52···O13	0.96	2.48	3.096 (4)	121
C5—H52···O13^iii	0.96	2.30	3.141 (4)	145
C15—H151···O21	0.93	2.32	2.910 (4)	121
C23—H231···O13^iii	0.94	2.43	3.365 (4)	175
C26—H261···O2^ii	0.93	2.45	3.358 (4)	166
C27—H271···O3^ii	0.93	2.55	3.261 (4)	134
C32—H322···O21^iv	0.96	2.58	3.520 (4)	167
C4—H43···O12^v	0.96	2.34	3.063 (4)	132
N18—H181···O12	0.84	2.29	2.966 (4)	138 (2)
C4—H42···O3^iii	0.96	2.55	3.379 (4)	145

Symmetry codes: (ii) x+1/2, −y+3/2, −z+3/4; (iii) −y+1, −x+1, −z+1/2; (iv) y+1/2, −x+1/2, z−1/4; (v) y−1/2, −x+3/2, z−1/4.

(apremilastmesitilene)

Crystal data

2(C22H24N2O7S)·C9H12	Dx = 1.387 Mg m^−3
Mr = 1041.17	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 62445 reflections
a = 13.2792 (1) Å	θ = 5–68°
c = 28.2737 (1) Å	µ = 1.58 mm^−1
V = 4985.70 (8) Å^3	T = 120 K
Z = 4	Block, colorless
F(000) = 2199.988	0.49 × 0.35 × 0.31 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4479 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.035
ω scans	θmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.49, Tmax = 0.61	k = −15→15
90441 measured reflections	l = −33→33
4516 independent reflections

Refinement

Refinement on F^2	H-atom parameters constrained
Least-squares matrix: full	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.04P)^2 + 2.04P] , where P = (max(Fo^2,0) + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.022	(Δ/σ)max = 0.001
wR(F^2) = 0.060	Δρmax = 0.21 e Å^−3
S = 0.86	Δρmin = −0.26 e Å^−3
4516 reflections	Extinction correction: Larson (1970), Equation 22
337 parameters	Extinction coefficient: 61 (8)
6 restraints	Absolute structure: Flack (1983), 1862 Friedel-pairs
Primary atom site location: Other	Absolute structure parameter: −0.003 (11)
Hydrogen site location: difference Fourier map

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.57862 (2)	0.18236 (2)	0.282453 (11)	0.0204
O2	0.66730 (7)	0.22420 (8)	0.30443 (3)	0.0263
O3	0.53532 (8)	0.09343 (8)	0.30348 (4)	0.0296
C4	0.60449 (11)	0.15805 (12)	0.22253 (5)	0.0287
C5	0.48529 (10)	0.27773 (10)	0.27897 (5)	0.0199
C6	0.44358 (10)	0.30955 (10)	0.32720 (4)	0.0192
N7	0.52323 (8)	0.35398 (8)	0.35716 (4)	0.0188
C8	0.55573 (10)	0.31021 (10)	0.39949 (4)	0.0184
C9	0.64526 (10)	0.36763 (10)	0.41484 (5)	0.0184
C10	0.66422 (10)	0.44234 (10)	0.38152 (4)	0.0193
C11	0.58556 (10)	0.43403 (10)	0.34421 (4)	0.0189
O12	0.51551 (7)	0.23868 (7)	0.41875 (3)	0.0226
O13	0.57507 (8)	0.48496 (7)	0.30884 (3)	0.0243
C14	0.70448 (10)	0.35641 (10)	0.45493 (4)	0.0194
C15	0.78599 (10)	0.42293 (11)	0.45998 (5)	0.0233
C16	0.80428 (11)	0.49674 (11)	0.42596 (5)	0.0246
C17	0.74369 (10)	0.50871 (10)	0.38608 (5)	0.0226
N18	0.67762 (9)	0.28104 (9)	0.48739 (4)	0.0211
C19	0.71998 (11)	0.26047 (11)	0.53052 (5)	0.0232
C20	0.66192 (12)	0.18431 (12)	0.55886 (5)	0.0287
O21	0.79692 (8)	0.30058 (8)	0.54498 (3)	0.0287
C22	0.35211 (10)	0.37771 (10)	0.32180 (5)	0.0194
C23	0.33704 (10)	0.43779 (10)	0.28178 (5)	0.0207
C24	0.25140 (10)	0.49712 (10)	0.27760 (5)	0.0212
C25	0.17836 (10)	0.49566 (10)	0.31376 (5)	0.0219
C26	0.19388 (10)	0.43612 (10)	0.35331 (5)	0.0228
C27	0.28041 (11)	0.37748 (11)	0.35718 (5)	0.0223
O28	0.23129 (7)	0.55953 (8)	0.24018 (3)	0.0268
C29	0.30457 (11)	0.56389 (11)	0.20284 (5)	0.0243
C30	0.27799 (12)	0.65034 (13)	0.17106 (6)	0.0351
O31	0.09501 (7)	0.55421 (8)	0.30633 (4)	0.0277
C32	0.01938 (11)	0.55043 (12)	0.34229 (5)	0.0279
C40	0.37984 (16)	0.37984 (16)	0.500000 (10)	0.0938
C41	0.45912 (13)	0.45912 (13)	0.5000	0.0434
C42	0.46605 (12)	0.52845 (14)	0.46313 (6)	0.0405
C43	0.53901 (12)	0.60302 (12)	0.46292 (5)	0.0312
C44	0.60652 (12)	0.60652 (12)	0.500000 (7)	0.0299
C45	0.54511 (17)	0.67888 (16)	0.42349 (7)	0.0535
H51	0.5165	0.3363	0.2630	0.0241*
H52	0.4300	0.2497	0.2600	0.0236*
H61	0.4212	0.2472	0.3453	0.0234*
H203	0.7040	0.1597	0.5845	0.0428*
H202	0.6017	0.2171	0.5719	0.0433*
H201	0.6428	0.1287	0.5384	0.0429*
H151	0.8300	0.4194	0.4866	0.0278*
H161	0.8616	0.5417	0.4302	0.0301*
H171	0.7555	0.5599	0.3632	0.0274*
H271	0.2894	0.3352	0.3850	0.0260*
H261	0.1449	0.4341	0.3774	0.0265*
H323	−0.0369	0.5929	0.3329	0.0417*
H321	0.0458	0.5774	0.3726	0.0419*
H322	−0.0035	0.4806	0.3469	0.0412*
H231	0.3867	0.4389	0.2572	0.0240*
H291	0.3729	0.5737	0.2163	0.0290*
H292	0.3036	0.4994	0.1850	0.0297*
H302	0.3268	0.6584	0.1454	0.0510*
H301	0.2740	0.7131	0.1886	0.0508*
H303	0.2132	0.6394	0.1546	0.0512*
H43	0.6400	0.2166	0.2094	0.0442*
H42	0.5409	0.1465	0.2061	0.0443*
H441	0.6570	0.6570	0.5000	0.0351*
H421	0.4195	0.5234	0.4374	0.0495*
H451	0.4788	0.7095	0.4188	0.0812*
H452	0.5926	0.7335	0.4323	0.0828*
H453	0.5650	0.6473	0.3936	0.0819*
H401	0.3728	0.3247	0.5264	0.1394*	0.5000
H402	0.3032	0.3940	0.5010	0.1407*	0.5000
H403	0.3688	0.3277	0.4724	0.1397*	0.5000
H41	0.6463	0.0981	0.2215	0.0435*
H181	0.6232	0.2388	0.4783	0.0254*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.01895 (16)	0.02090 (17)	0.02129 (15)	0.00234 (12)	−0.00270 (12)	−0.00033 (12)
O2	0.0209 (5)	0.0315 (5)	0.0266 (5)	0.0012 (4)	−0.0046 (4)	−0.0026 (4)
O3	0.0288 (5)	0.0246 (5)	0.0355 (5)	0.0004 (4)	−0.0030 (4)	0.0069 (4)
C4	0.0283 (8)	0.0317 (8)	0.0260 (7)	0.0052 (6)	−0.0022 (6)	−0.0076 (6)
C5	0.0197 (6)	0.0202 (6)	0.0196 (6)	0.0021 (5)	−0.0021 (5)	0.0008 (5)
C6	0.0193 (7)	0.0192 (6)	0.0191 (6)	−0.0014 (5)	−0.0006 (5)	0.0015 (5)
N7	0.0190 (5)	0.0196 (5)	0.0179 (5)	−0.0009 (4)	0.0008 (4)	0.0018 (4)
C8	0.0190 (6)	0.0187 (6)	0.0175 (6)	0.0026 (5)	0.0025 (5)	−0.0002 (5)
C9	0.0172 (6)	0.0187 (6)	0.0193 (6)	0.0017 (5)	0.0026 (5)	−0.0007 (5)
C10	0.0200 (6)	0.0186 (6)	0.0193 (6)	0.0023 (5)	0.0033 (5)	−0.0009 (5)
C11	0.0200 (6)	0.0180 (6)	0.0187 (6)	0.0014 (5)	0.0038 (5)	−0.0002 (5)
O12	0.0241 (5)	0.0221 (5)	0.0217 (5)	−0.0027 (4)	0.0009 (4)	0.0046 (4)
O13	0.0282 (5)	0.0234 (5)	0.0212 (5)	−0.0009 (4)	−0.0003 (4)	0.0061 (4)
C14	0.0192 (6)	0.0203 (6)	0.0186 (6)	0.0032 (5)	0.0022 (5)	−0.0004 (5)
C15	0.0208 (7)	0.0256 (7)	0.0233 (6)	0.0014 (6)	−0.0020 (5)	0.0001 (6)
C16	0.0196 (7)	0.0243 (7)	0.0301 (7)	−0.0023 (5)	0.0009 (6)	−0.0004 (6)
C17	0.0235 (7)	0.0203 (7)	0.0242 (7)	−0.0014 (5)	0.0037 (5)	0.0027 (5)
N18	0.0218 (6)	0.0220 (6)	0.0194 (5)	−0.0013 (4)	−0.0013 (5)	0.0030 (5)
C19	0.0259 (7)	0.0243 (7)	0.0194 (6)	0.0069 (6)	0.0020 (6)	−0.0008 (6)
C20	0.0343 (8)	0.0302 (8)	0.0217 (7)	0.0026 (7)	0.0011 (6)	0.0047 (6)
O21	0.0275 (5)	0.0360 (6)	0.0227 (5)	−0.0009 (5)	−0.0047 (4)	0.0010 (4)
C22	0.0184 (6)	0.0190 (6)	0.0207 (6)	−0.0012 (5)	−0.0011 (5)	0.0001 (5)
C23	0.0198 (6)	0.0215 (7)	0.0209 (6)	0.0003 (5)	0.0023 (5)	0.0005 (5)
C24	0.0220 (6)	0.0215 (7)	0.0200 (6)	−0.0002 (5)	−0.0003 (5)	0.0023 (5)
C25	0.0187 (6)	0.0219 (7)	0.0251 (7)	0.0010 (5)	0.0002 (5)	−0.0010 (5)
C26	0.0210 (7)	0.0260 (7)	0.0213 (6)	−0.0019 (5)	0.0045 (5)	−0.0015 (5)
C27	0.0225 (7)	0.0253 (7)	0.0193 (6)	−0.0020 (5)	−0.0004 (5)	0.0028 (5)
O28	0.0247 (5)	0.0310 (6)	0.0246 (5)	0.0077 (4)	0.0047 (4)	0.0102 (4)
C29	0.0241 (7)	0.0277 (7)	0.0212 (6)	0.0009 (6)	0.0027 (5)	0.0053 (5)
C30	0.0362 (9)	0.0387 (9)	0.0304 (8)	0.0063 (7)	0.0019 (7)	0.0133 (7)
O31	0.0214 (5)	0.0316 (5)	0.0302 (5)	0.0076 (4)	0.0058 (4)	0.0043 (4)
C32	0.0186 (7)	0.0332 (8)	0.0318 (7)	0.0011 (6)	0.0040 (6)	−0.0041 (6)
C40	0.0762 (16)	0.0762 (16)	0.129 (3)	−0.052 (2)	0.071 (2)	−0.071 (2)
C41	0.0350 (8)	0.0350 (8)	0.0604 (16)	−0.0101 (10)	0.0258 (9)	−0.0258 (9)
C42	0.0256 (8)	0.0541 (11)	0.0417 (9)	0.0063 (7)	0.0014 (7)	−0.0258 (9)
C43	0.0298 (8)	0.0323 (8)	0.0315 (8)	0.0089 (6)	0.0026 (7)	−0.0050 (6)
C44	0.0254 (6)	0.0254 (6)	0.0388 (12)	0.0005 (8)	0.0032 (6)	−0.0032 (6)
C45	0.0669 (13)	0.0530 (12)	0.0406 (10)	0.0251 (10)	0.0020 (9)	0.0073 (9)

Geometric parameters (Å, º)

S1—O2	1.4428 (10)	C23—C24	1.3885 (19)
S1—O3	1.4418 (11)	C23—H231	0.959
S1—C4	1.7585 (14)	C24—C25	1.4095 (19)
S1—C5	1.7747 (13)	C24—O28	1.3702 (16)
C4—H43	0.982	C25—C26	1.385 (2)
C4—H42	0.975	C25—O31	1.3687 (16)
C4—H41	0.971	C26—C27	1.392 (2)
C5—C6	1.5312 (18)	C26—H261	0.942
C5—H51	0.990	C27—H271	0.973
C5—H52	0.982	O28—C29	1.4370 (16)
C6—N7	1.4780 (16)	C29—C30	1.500 (2)
C6—C22	1.5226 (18)	C29—H291	0.993
C6—H61	1.018	C29—H292	0.994
N7—C8	1.3987 (17)	C30—H302	0.978
N7—C11	1.3960 (17)	C30—H301	0.971
C8—C9	1.4775 (18)	C30—H303	0.990
C8—O12	1.2182 (16)	O31—C32	1.4301 (17)
C9—C10	1.3912 (18)	C32—H323	0.973
C9—C14	1.3875 (18)	C32—H321	0.994
C10—C11	1.4884 (18)	C32—H322	0.985
C10—C17	1.3810 (19)	C40—H403^i	1.053
C11—O13	1.2153 (16)	C40—H401^i	1.050
C14—C15	1.4044 (19)	C40—H402^i	1.036
C14—N18	1.4040 (17)	C40—C41	1.489 (4)
C15—C16	1.395 (2)	C40—H401	1.050
C15—H151	0.954	C40—H402	1.036
C16—C17	1.394 (2)	C40—H403	1.053
C16—H161	0.975	C41—C42^i	1.394 (2)
C17—H171	0.951	C41—C42	1.394 (2)
N18—C19	1.3707 (17)	C42—C43	1.385 (2)
N18—H181	0.950	C42—H421	0.956
C19—C20	1.503 (2)	C43—C44	1.3801 (19)
C19—O21	1.2225 (18)	C43—C45	1.505 (2)
C20—H203	0.973	C44—H441	0.948
C20—H202	0.982	C45—H451	0.978
C20—H201	0.972	C45—H452	0.993
C22—C23	1.3990 (18)	C45—H453	0.979
C22—C27	1.3808 (19)
O2—S1—O3	117.60 (6)	C23—C24—O28	124.65 (12)
O2—S1—C4	109.03 (7)	C25—C24—O28	115.74 (12)
O3—S1—C4	108.96 (7)	C24—C25—C26	119.41 (12)
O2—S1—C5	108.61 (6)	C24—C25—O31	115.93 (12)
O3—S1—C5	109.20 (6)	C26—C25—O31	124.65 (12)
C4—S1—C5	102.35 (7)	C25—C26—C27	120.36 (12)
S1—C4—H43	108.3	C25—C26—H261	119.9
S1—C4—H42	108.5	C27—C26—H261	119.8
H43—C4—H42	111.1	C26—C27—C22	120.72 (13)
S1—C4—H41	106.9	C26—C27—H271	119.1
H43—C4—H41	111.3	C22—C27—H271	120.2
H42—C4—H41	110.6	C24—O28—C29	117.36 (10)
S1—C5—C6	113.58 (9)	O28—C29—C30	108.15 (12)
S1—C5—H51	107.1	O28—C29—H291	110.0
C6—C5—H51	109.9	C30—C29—H291	110.2
S1—C5—H52	106.4	O28—C29—H292	109.2
C6—C5—H52	108.6	C30—C29—H292	110.7
H51—C5—H52	111.2	H291—C29—H292	108.7
C5—C6—N7	111.21 (10)	C29—C30—H302	111.8
C5—C6—C22	111.31 (10)	C29—C30—H301	111.3
N7—C6—C22	113.02 (10)	H302—C30—H301	108.7
C5—C6—H61	109.3	C29—C30—H303	112.0
N7—C6—H61	104.2	H302—C30—H303	104.1
C22—C6—H61	107.5	H301—C30—H303	108.6
C6—N7—C8	123.04 (11)	C25—O31—C32	116.03 (11)
C6—N7—C11	125.31 (11)	O31—C32—H323	109.0
C8—N7—C11	110.97 (11)	O31—C32—H321	110.7
N7—C8—C9	106.57 (11)	H323—C32—H321	107.3
N7—C8—O12	124.84 (12)	O31—C32—H322	110.2
C9—C8—O12	128.59 (12)	H323—C32—H322	110.2
C8—C9—C10	108.34 (11)	H321—C32—H322	109.5
C8—C9—C14	129.84 (12)	H403^i—C40—H401^i	93.2
C10—C9—C14	121.81 (12)	H403^i—C40—H402^i	90.1
C9—C10—C11	107.46 (11)	H401^i—C40—H402^i	91.1
C9—C10—C17	122.02 (12)	H403^i—C40—C41	124.3
C11—C10—C17	130.52 (12)	H401^i—C40—C41	123.8
C10—C11—N7	106.66 (11)	H402^i—C40—C41	124.5
C10—C11—O13	128.48 (12)	H403^i—C40—H401	47.0
N7—C11—O13	124.86 (12)	H401^i—C40—H401	112.3
C9—C14—C15	116.90 (12)	H402^i—C40—H401	49.4
C9—C14—N18	117.80 (12)	C41—C40—H401	123.8
C15—C14—N18	125.29 (12)	H403^i—C40—H402	50.2
C14—C15—C16	120.40 (13)	H401^i—C40—H402	49.4
C14—C15—H151	121.4	H402^i—C40—H402	111.0
C16—C15—H151	118.1	C41—C40—H402	124.5
C15—C16—C17	122.51 (13)	H401—C40—H402	91.1
C15—C16—H161	118.8	H403^i—C40—H403	111.5
C17—C16—H161	118.7	H401^i—C40—H403	47.0
C16—C17—C10	116.34 (12)	H402^i—C40—H403	50.2
C16—C17—H171	122.4	C41—C40—H403	124.3
C10—C17—H171	121.2	H401—C40—H403	93.2
C14—N18—C19	128.28 (12)	H402—C40—H403	90.1
C14—N18—H181	115.9	C40—C41—C42^i	120.91 (11)
C19—N18—H181	115.8	C40—C41—C42	120.91 (11)
N18—C19—C20	113.44 (12)	C42^i—C41—C42	118.2 (2)
N18—C19—O21	123.62 (13)	C41—C42—C43	121.42 (17)
C20—C19—O21	122.93 (12)	C41—C42—H421	118.7
C19—C20—H203	109.2	C43—C42—H421	119.9
C19—C20—H202	108.6	C42—C43—C44	118.37 (16)
H203—C20—H202	109.6	C42—C43—C45	121.27 (16)
C19—C20—H201	109.1	C44—C43—C45	120.35 (17)
H203—C20—H201	109.8	C43—C44—C43^i	122.2 (2)
H202—C20—H201	110.4	C43—C44—H441	118.9
C6—C22—C23	122.28 (11)	C43^i—C44—H441	118.9
C6—C22—C27	118.44 (12)	C43—C45—H451	109.2
C23—C22—C27	119.25 (12)	C43—C45—H452	109.8
C22—C23—C24	120.64 (12)	H451—C45—H452	107.6
C22—C23—H231	119.8	C43—C45—H453	111.5
C24—C23—H231	119.5	H451—C45—H453	107.7
C23—C24—C25	119.61 (12)	H452—C45—H453	110.9

Symmetry code: (i) y, x, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H51···O13	0.99	2.49	3.116 (2)	121
C5—H51···O13^ii	0.99	2.35	3.185 (2)	142
C5—H52···O21^iii	0.98	2.45	3.422 (2)	172
C27—H271···O2^iii	0.97	2.49	3.213 (2)	131
C26—H261···O3^iii	0.94	2.46	3.396 (2)	170
C23—H231···O13^ii	0.96	2.53	3.490 (2)	175
C4—H43···O2^ii	0.98	2.40	3.337 (2)	158
C40—H401···O2^iv	1.05	2.58	3.499 (2)	146
C4—H41···O12^v	0.97	2.45	3.286 (2)	144
N18—H181···O12	0.95	2.21	2.952 (2)	134

Symmetry codes: (ii) −y+1, −x+1, −z+1/2; (iii) x−1/2, −y+1/2, −z+3/4; (iv) −y+1/2, x−1/2, z+1/4; (v) y+1/2, −x+1/2, z−1/4.

(apremilastmetaxylene)

Crystal data

C22H24N2O7S·0.5(C8H10)	Dx = 1.387 Mg m^−3
Mr = 513.59	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 69131 reflections
a = 12.9696 (1) Å	θ = 5–68°
c = 29.2499 (1) Å	µ = 1.59 mm^−1
V = 4920.14 (8) Å^3	T = 120 K
Z = 8	Block, colorless
F(000) = 2168	0.33 × 0.28 × 0.25 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4439 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.037
ω scans	θmax = 67.6°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.56, Tmax = 0.68	k = −15→15
100964 measured reflections	l = −32→34
4454 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.036	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.02P)^2 + 6.16P] , where P = (max(Fo^2,0) + 2Fc^2)/3
wR(F^2) = 0.091	(Δ/σ)max = 0.001
S = 1.12	Δρmax = 0.20 e Å^−3
4453 reflections	Δρmin = −0.23 e Å^−3
362 parameters	Absolute structure: Flack (1983), 1832 Friedel-pairs
125 restraints	Absolute structure parameter: 0.03 (2)
Primary atom site location: Other

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C40	0.6710 (6)	0.5593 (6)	0.5661 (3)	0.0594	0.5000
C41	0.4691 (7)	0.5885 (6)	0.4199 (3)	0.0602	0.5000
C42	0.4860 (6)	0.5383 (6)	0.4649 (3)	0.0448	0.5000
C43	0.5667 (19)	0.571 (2)	0.4928 (5)	0.0373	0.5000
C44	0.5815 (5)	0.5255 (5)	0.5356 (2)	0.0434	0.5000
C45	0.5155 (6)	0.4481 (5)	0.5503 (3)	0.0425	0.5000
C46	0.4358 (17)	0.4139 (17)	0.5219 (7)	0.0463	0.5000
C47	0.4215 (17)	0.4588 (18)	0.4792 (6)	0.0463	0.5000
S1	0.59258 (5)	0.16872 (5)	0.28452 (2)	0.0212
O2	0.68444 (14)	0.21493 (14)	0.30385 (6)	0.0283
O3	0.54917 (15)	0.08080 (14)	0.30775 (7)	0.0296
C4	0.6189 (2)	0.1357 (2)	0.22751 (9)	0.0327
C5	0.49641 (19)	0.26539 (19)	0.27892 (8)	0.0200
C6	0.45191 (19)	0.29989 (19)	0.32485 (8)	0.0193
N7	0.53234 (16)	0.34636 (15)	0.35428 (7)	0.0185
C8	0.56145 (19)	0.30486 (18)	0.39650 (8)	0.0184
C9	0.65096 (19)	0.36583 (19)	0.41219 (8)	0.0183
C10	0.6736 (2)	0.43869 (19)	0.37903 (8)	0.0201
C11	0.59690 (19)	0.42708 (18)	0.34173 (8)	0.0190
O12	0.51867 (14)	0.23342 (13)	0.41545 (6)	0.0228
O13	0.58875 (15)	0.47698 (13)	0.30636 (6)	0.0250
C14	0.70720 (19)	0.35921 (18)	0.45244 (8)	0.0187
C15	0.78905 (19)	0.4284 (2)	0.45773 (9)	0.0245
C16	0.8115 (2)	0.5000 (2)	0.42382 (10)	0.0274
C17	0.7539 (2)	0.5079 (2)	0.38358 (9)	0.0245
N18	0.67714 (17)	0.28524 (16)	0.48458 (7)	0.0224
C19	0.7192 (2)	0.2664 (2)	0.52696 (9)	0.0242
C20	0.6582 (2)	0.1912 (2)	0.55505 (9)	0.0321
O21	0.79719 (14)	0.30845 (15)	0.54103 (6)	0.0296
C22	0.35946 (19)	0.37069 (19)	0.31878 (8)	0.0201
C23	0.34297 (19)	0.42797 (19)	0.27877 (9)	0.0229
C24	0.2569 (2)	0.4900 (2)	0.27427 (9)	0.0244
C25	0.1834 (2)	0.49466 (19)	0.30987 (9)	0.0241
C26	0.2001 (2)	0.4383 (2)	0.34941 (9)	0.0246
C27	0.2879 (2)	0.3768 (2)	0.35362 (9)	0.0226
O28	0.23479 (14)	0.55103 (16)	0.23704 (7)	0.0320
C29	0.3117 (2)	0.5567 (2)	0.20161 (10)	0.0342
C30	0.2841 (3)	0.6454 (3)	0.17110 (13)	0.0529
O31	0.09927 (14)	0.55572 (15)	0.30243 (7)	0.0317
C32	0.0267 (2)	0.5629 (3)	0.33924 (10)	0.0379
H52	0.4417	0.2377	0.2601	0.0242*
H51	0.5272	0.3249	0.2638	0.0237*
H61	0.4267	0.2371	0.3412	0.0219*
H201	0.7012	0.1678	0.5804	0.0471*
H203	0.6397	0.1337	0.5350	0.0469*
H202	0.5968	0.2248	0.5664	0.0476*
H151	0.8288	0.4265	0.4837	0.0278*
H161	0.8670	0.5441	0.4279	0.0325*
H171	0.7693	0.5565	0.3611	0.0307*
H271	0.2970	0.3375	0.3804	0.0249*
H261	0.1525	0.4422	0.3738	0.0286*
H321	−0.0277	0.6092	0.3305	0.0530*
H322	−0.0001	0.4961	0.3465	0.0531*
H323	0.0602	0.5907	0.3665	0.0525*
H231	0.3919	0.4243	0.2536	0.0256*
H292	0.3131	0.4921	0.1860	0.0404*
H291	0.3779	0.5682	0.2160	0.0402*
H301	0.3415	0.6550	0.1497	0.0700*
H303	0.2227	0.6296	0.1537	0.0699*
H302	0.2743	0.7069	0.1891	0.0693*
H43	0.5531	0.1184	0.2146	0.0500*
H42	0.6636	0.0770	0.2285	0.0499*
H41	0.6501	0.1946	0.2134	0.0500*
H411	0.4110	0.5584	0.4053	0.0759*	0.5000
H412	0.4571	0.6600	0.4243	0.0759*	0.5000
H413	0.5285	0.5792	0.4013	0.0759*	0.5000
H401	0.6699	0.5221	0.5941	0.0711*	0.5000
H402	0.6656	0.6311	0.5722	0.0711*	0.5000
H403	0.7338	0.5459	0.5505	0.0711*	0.5000
H431	0.6127	0.6230	0.4824	0.0457*	0.5000
H451	0.5245	0.4175	0.5798	0.0513*	0.5000
H461	0.3912	0.3603	0.5318	0.0536*	0.5000
H471	0.3675	0.4356	0.4598	0.0566*	0.5000
H181	0.6207	0.2427	0.4761	0.0276*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C40	0.044 (4)	0.049 (4)	0.085 (6)	0.009 (3)	−0.007 (4)	−0.024 (4)
C41	0.062 (5)	0.050 (4)	0.069 (5)	0.028 (4)	0.013 (4)	−0.003 (4)
C42	0.036 (6)	0.045 (6)	0.054 (5)	0.011 (4)	−0.003 (4)	−0.019 (5)
C43	0.029 (5)	0.031 (6)	0.051 (11)	0.007 (3)	0.005 (7)	−0.012 (6)
C44	0.037 (5)	0.023 (4)	0.070 (5)	0.009 (3)	0.017 (4)	−0.013 (4)
C45	0.040 (5)	0.028 (4)	0.060 (6)	0.018 (4)	0.020 (4)	−0.011 (4)
C46	0.029 (8)	0.034 (6)	0.076 (8)	0.006 (3)	0.008 (5)	−0.021 (5)
C47	0.029 (5)	0.045 (10)	0.065 (7)	0.001 (5)	0.009 (5)	−0.020 (6)
S1	0.0220 (3)	0.0220 (3)	0.0196 (3)	0.0039 (2)	−0.0020 (2)	−0.0027 (2)
O2	0.0218 (9)	0.0348 (11)	0.0281 (10)	0.0021 (8)	−0.0053 (8)	−0.0032 (8)
O3	0.0325 (10)	0.0229 (9)	0.0335 (10)	0.0038 (8)	−0.0006 (8)	0.0029 (8)
C4	0.0323 (16)	0.0377 (16)	0.0281 (14)	0.0056 (12)	0.0038 (12)	−0.0103 (12)
C5	0.0204 (12)	0.0208 (12)	0.0190 (11)	0.0041 (9)	−0.0013 (10)	0.0008 (10)
C6	0.0204 (12)	0.0206 (12)	0.0169 (11)	0.0002 (10)	−0.0010 (10)	−0.0001 (9)
N7	0.0215 (11)	0.0172 (10)	0.0167 (10)	0.0006 (8)	0.0012 (8)	0.0022 (8)
C8	0.0215 (12)	0.0184 (12)	0.0155 (11)	0.0044 (10)	0.0030 (9)	−0.0019 (9)
C9	0.0184 (12)	0.0185 (12)	0.0180 (12)	0.0028 (9)	0.0046 (9)	−0.0017 (9)
C10	0.0229 (13)	0.0175 (12)	0.0198 (11)	0.0023 (10)	0.0042 (10)	−0.0008 (9)
C11	0.0209 (12)	0.0166 (12)	0.0196 (12)	0.0015 (10)	0.0044 (10)	−0.0007 (10)
O12	0.0251 (9)	0.0215 (9)	0.0218 (9)	−0.0048 (7)	0.0022 (7)	0.0033 (7)
O13	0.0330 (10)	0.0222 (9)	0.0197 (9)	−0.0007 (8)	0.0024 (8)	0.0056 (7)
C14	0.0207 (12)	0.0172 (12)	0.0182 (12)	0.0055 (10)	0.0024 (9)	0.0002 (9)
C15	0.0223 (13)	0.0252 (14)	0.0260 (13)	0.0009 (11)	−0.0013 (10)	−0.0009 (10)
C16	0.0215 (13)	0.0226 (13)	0.0380 (15)	−0.0044 (11)	−0.0009 (12)	0.0038 (11)
C17	0.0260 (14)	0.0211 (13)	0.0263 (14)	−0.0017 (11)	0.0020 (11)	0.0050 (11)
N18	0.0218 (11)	0.0254 (11)	0.0200 (10)	−0.0047 (9)	0.0005 (9)	0.0021 (9)
C19	0.0263 (14)	0.0267 (14)	0.0197 (12)	0.0041 (11)	0.0011 (11)	−0.0017 (11)
C20	0.0341 (16)	0.0408 (17)	0.0216 (13)	−0.0032 (13)	0.0005 (12)	0.0068 (12)
O21	0.0291 (10)	0.0375 (11)	0.0224 (9)	−0.0044 (9)	−0.0023 (8)	−0.0006 (8)
C22	0.0200 (13)	0.0192 (12)	0.0211 (12)	−0.0021 (10)	0.0004 (10)	−0.0006 (10)
C23	0.0220 (13)	0.0215 (13)	0.0250 (12)	0.0019 (10)	0.0071 (10)	0.0045 (10)
C24	0.0195 (12)	0.0249 (14)	0.0290 (13)	0.0005 (10)	0.0023 (10)	0.0071 (11)
C25	0.0191 (12)	0.0199 (13)	0.0333 (14)	0.0021 (10)	0.0025 (11)	−0.0030 (11)
C26	0.0211 (13)	0.0258 (14)	0.0268 (13)	−0.0040 (10)	0.0062 (11)	−0.0038 (11)
C27	0.0248 (14)	0.0237 (13)	0.0192 (12)	−0.0030 (10)	0.0031 (10)	−0.0012 (10)
O28	0.0217 (10)	0.0366 (11)	0.0378 (11)	0.0063 (8)	0.0067 (8)	0.0180 (9)
C29	0.0250 (14)	0.0444 (17)	0.0332 (15)	0.0011 (13)	0.0040 (12)	0.0197 (13)
C30	0.0320 (17)	0.068 (3)	0.059 (2)	0.0053 (16)	0.0048 (16)	0.042 (2)
O31	0.0209 (9)	0.0331 (11)	0.0410 (11)	0.0076 (8)	0.0072 (8)	0.0018 (9)
C32	0.0209 (14)	0.058 (2)	0.0349 (16)	0.0093 (14)	0.0031 (12)	−0.0188 (14)

Geometric parameters (Å, º)

C40—C41^i	1.638 (12)	C8—C9	1.478 (3)
C40—C44	1.528 (9)	C8—O12	1.214 (3)
C40—H401	0.950	C9—C10	1.386 (3)
C40—H402	0.950	C9—C14	1.388 (3)
C40—H403	0.950	C10—C11	1.484 (3)
C41—H451^i	1.066	C10—C17	1.381 (4)
C41—C44^i	1.497 (11)	C11—O13	1.225 (3)
C41—C45^i	1.315 (12)	C14—C15	1.398 (4)
C41—C42	1.485 (12)	C14—N18	1.399 (3)
C41—H411	0.950	C15—C16	1.390 (4)
C41—H412	0.950	C15—H151	0.919
C41—H413	0.950	C16—C17	1.398 (4)
C42—C46^i	1.671 (12)	C16—H161	0.926
C42—C43^i	1.697 (11)	C17—H171	0.933
C42—C43	1.393 (7)	N18—C19	1.376 (3)
C42—C47	1.393 (7)	N18—H181	0.950
C43—H431^i	1.161	C19—C20	1.500 (4)
C43—C44^i	0.996 (15)	C19—O21	1.220 (3)
C43—C44	1.395 (6)	C20—H201	0.976
C43—H431	0.950	C20—H203	0.979
C44—C45	1.388 (6)	C20—H202	0.967
C45—C47^i	1.187 (19)	C22—C23	1.403 (3)
C45—C46	1.399 (7)	C22—C27	1.381 (3)
C45—H451	0.956	C23—C24	1.382 (4)
C46—C46^i	1.34 (3)	C23—H231	0.972
C46—H471^i	0.806	C24—C25	1.413 (4)
C46—C47	1.389 (6)	C24—O28	1.377 (3)
C46—H461	0.950	C25—C26	1.385 (4)
C47—H461^i	1.226	C25—O31	1.365 (3)
C47—C47^i	1.39 (2)	C26—C27	1.395 (4)
C47—H471	0.951	C26—H261	0.946
S1—O2	1.4485 (19)	C27—H271	0.943
S1—O3	1.442 (2)	O28—C29	1.440 (3)
S1—C4	1.755 (3)	C29—C30	1.499 (4)
S1—C5	1.776 (2)	C29—H292	0.954
C4—H43	0.959	C29—H291	0.968
C4—H42	0.958	C30—H301	0.981
C4—H41	0.958	C30—H303	0.966
C5—C6	1.529 (3)	C30—H302	0.964
C5—H52	0.968	O31—C32	1.433 (3)
C5—H51	0.975	C32—H321	0.960
C6—N7	1.481 (3)	C32—H322	0.958
C6—C22	1.521 (3)	C32—H323	0.976
C6—H61	0.999	H411—H451^i	0.626
N7—C8	1.399 (3)	H461—H471^i	0.633
N7—C11	1.390 (3)
C41^i—C40—C44	56.3 (5)	O2—S1—O3	117.68 (11)
C41^i—C40—H401	54.0	O2—S1—C4	108.19 (13)
C44—C40—H401	110.3	O3—S1—C4	109.30 (14)
C41^i—C40—H402	127.2	O2—S1—C5	108.75 (12)
C44—C40—H402	109.6	O3—S1—C5	109.12 (12)
H401—C40—H402	109.5	C4—S1—C5	102.76 (12)
C41^i—C40—H403	123.4	S1—C4—H43	105.0
C44—C40—H403	108.6	S1—C4—H42	106.4
H401—C40—H403	109.5	H43—C4—H42	111.4
H402—C40—H403	109.5	S1—C4—H41	107.2
H451^i—C41—C44^i	104.6	H43—C4—H41	113.2
H451^i—C41—C40^i	162.7	H42—C4—H41	113.0
C44^i—C41—C40^i	58.1 (5)	S1—C5—C6	112.98 (16)
H451^i—C41—C45^i	45.9	S1—C5—H52	107.8
C44^i—C41—C45^i	58.7 (4)	C6—C5—H52	109.4
C40^i—C41—C45^i	116.9 (7)	S1—C5—H51	108.2
H451^i—C41—C42	75.2	C6—C5—H51	108.8
C44^i—C41—C42	29.5 (3)	H52—C5—H51	109.6
C40^i—C41—C42	87.6 (6)	C5—C6—N7	111.3 (2)
C45^i—C41—C42	29.3 (3)	C5—C6—C22	111.82 (19)
H451^i—C41—H411	35.6	N7—C6—C22	112.18 (19)
C44^i—C41—H411	139.0	C5—C6—H61	107.8
C40^i—C41—H411	161.4	N7—C6—H61	106.5
C45^i—C41—H411	80.7	C22—C6—H61	106.8
C42—C41—H411	109.7	C6—N7—C8	123.1 (2)
H451^i—C41—H412	131.1	C6—N7—C11	125.3 (2)
C44^i—C41—H412	91.2	C8—N7—C11	111.1 (2)
C40^i—C41—H412	56.2	N7—C8—C9	106.3 (2)
C45^i—C41—H412	125.4	N7—C8—O12	125.0 (2)
C42—C41—H412	109.3	C9—C8—O12	128.7 (2)
H451^i—C41—H413	114.6	C8—C9—C10	108.3 (2)
C44^i—C41—H413	95.4	C8—C9—C14	130.0 (2)
C40^i—C41—H413	69.3	C10—C9—C14	121.6 (2)
C45^i—C41—H413	117.1	C9—C10—C11	107.7 (2)
C42—C41—H413	109.4	C9—C10—C17	122.4 (2)
H411—C41—H412	109.5	C11—C10—C17	129.9 (2)
H411—C41—H413	109.5	C10—C11—N7	106.61 (19)
H412—C41—H413	109.5	C10—C11—O13	128.7 (2)
C41—C42—C46^i	118.1 (7)	N7—C11—O13	124.7 (2)
C41—C42—C43^i	130.4 (7)	C9—C14—C15	116.9 (2)
C46^i—C42—C43^i	111.5 (8)	C9—C14—N18	117.8 (2)
C41—C42—C43	119.9 (6)	C15—C14—N18	125.3 (2)
C46^i—C42—C43	121.8 (8)	C14—C15—C16	120.6 (2)
C43^i—C42—C43	11.2 (10)	C14—C15—H151	120.0
C41—C42—C47	120.1 (6)	C16—C15—H151	119.4
C46^i—C42—C47	6 (2)	C15—C16—C17	122.5 (2)
C43^i—C42—C47	109.3 (4)	C15—C16—H161	118.9
C43—C42—C47	119.98 (9)	C17—C16—H161	118.5
H431^i—C43—C42	168.1	C16—C17—C10	115.9 (2)
H431^i—C43—C42^i	89.1	C16—C17—H171	122.0
C42—C43—C42^i	93.9 (5)	C10—C17—H171	122.2
H431^i—C43—C44^i	142.4	C14—N18—C19	128.1 (2)
C42—C43—C44^i	31.9 (5)	C14—N18—H181	115.9
C42^i—C43—C44^i	125.4 (3)	C19—N18—H181	116.0
H431^i—C43—C44	63.4	N18—C19—C20	113.6 (2)
C42—C43—C44	120.01 (9)	N18—C19—O21	123.5 (2)
C42^i—C43—C44	26.2 (5)	C20—C19—O21	122.9 (2)
C44^i—C43—C44	151.4 (7)	C19—C20—H201	108.5
H431^i—C43—H431	58.3	C19—C20—H203	107.2
C42—C43—H431	120.0	H201—C20—H203	111.0
C42^i—C43—H431	146.1	C19—C20—H202	109.2
C44^i—C43—H431	88.5	H201—C20—H202	110.5
C44—C43—H431	120.0	H203—C20—H202	110.3
C40—C44—C41^i	65.6 (5)	C6—C22—C23	122.5 (2)
C40—C44—C43	120.4 (5)	C6—C22—C27	118.6 (2)
C41^i—C44—C43	174.0 (6)	C23—C22—C27	118.9 (2)
C40—C44—C43^i	115.9 (6)	C22—C23—C24	120.7 (2)
C41^i—C44—C43^i	174 (2)	C22—C23—H231	120.4
C43—C44—C43^i	7 (3)	C24—C23—H231	118.9
C40—C44—C45	119.6 (5)	C23—C24—C25	120.0 (2)
C41^i—C44—C45	54.0 (5)	C23—C24—O28	125.3 (2)
C43—C44—C45	119.97 (9)	C25—C24—O28	114.7 (2)
C43^i—C44—C45	124.2 (5)	C24—C25—C26	119.1 (2)
C44—C45—C41^i	67.2 (6)	C24—C25—O31	116.5 (2)
C44—C45—C47^i	111.5 (6)	C26—C25—O31	124.4 (2)
C41^i—C45—C47^i	171.6 (18)	C25—C26—C27	120.2 (2)
C44—C45—C46	119.97 (9)	C25—C26—H261	120.0
C41^i—C45—C46	172.5 (7)	C27—C26—H261	119.8
C47^i—C45—C46	10 (2)	C26—C27—C22	121.1 (2)
C44—C45—H451	120.4	C26—C27—H271	119.0
C41^i—C45—H451	53.2	C22—C27—H271	119.9
C47^i—C45—H451	127.7	C24—O28—C29	117.0 (2)
C46—C45—H451	119.7	O28—C29—C30	107.6 (2)
C42^i—C46—C45	25.4 (4)	O28—C29—H292	108.3
C42^i—C46—C46^i	105.7 (7)	C30—C29—H292	113.1
C45—C46—C46^i	131.1 (7)	O28—C29—H291	108.0
C42^i—C46—H471^i	105.5	C30—C29—H291	110.7
C45—C46—H471^i	81.0	H292—C29—H291	109.0
C46^i—C46—H471^i	142.4	C29—C30—H301	107.2
C42^i—C46—C47	94.6 (4)	C29—C30—H303	110.4
C45—C46—C47	120.01 (9)	H301—C30—H303	108.5
C46^i—C46—C47	13.1 (13)	C29—C30—H302	110.0
H471^i—C46—C47	155.5	H301—C30—H302	110.0
C42^i—C46—H461	145.4	H303—C30—H302	110.8
C45—C46—H461	120.0	C25—O31—C32	116.3 (2)
C46^i—C46—H461	108.5	O31—C32—H321	108.9
H471^i—C46—H461	41.2	O31—C32—H322	110.2
C47—C46—H461	120.0	H321—C32—H322	111.0
H461^i—C47—C47^i	101.9	O31—C32—H323	110.2
H461^i—C47—C42	147.1	H321—C32—H323	108.3
C47^i—C47—C42	108.1 (4)	H322—C32—H323	108.3
H461^i—C47—C46	91.3	H451^i—H411—C41	82.3
C47^i—C47—C46	13.0 (12)	C43^i—H431—C43	20.4
C42—C47—C46	120.02 (9)	H411^i—H451—C41^i	62.1
H461^i—C47—C45^i	116.1	H411^i—H451—C45	140.5
C47^i—C47—C45^i	138.5 (11)	C41^i—H451—C45	80.9
C42—C47—C45^i	31.4 (4)	H471^i—H461—C47^i	49.9
C46—C47—C45^i	151.1 (5)	H471^i—H461—C46	57.1
H461^i—C47—H471	30.6	C47^i—H461—C46	8.2
C47^i—C47—H471	131.8	H461^i—H471—C47	99.5
C42—C47—H471	119.8	H461^i—H471—C46^i	81.7
C46—C47—H471	120.2	C47—H471—C46^i	18.4
C45^i—C47—H471	88.6

Symmetry code: (i) y, x, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H52···O21^ii	0.97	2.47	3.432 (8)	172
C5—H51···O13	0.98	2.47	3.100 (8)	122
C5—H51···O13^iii	0.98	2.34	3.149 (8)	140
C15—H151···O21	0.92	2.31	2.892 (8)	121
C27—H271···O2^ii	0.94	2.51	3.247 (8)	135
C26—H261···O3^ii	0.95	2.43	3.357 (8)	168
C23—H231···O13^iii	0.97	2.45	3.420 (8)	176
C4—H42···O12^iv	0.96	2.40	3.084 (8)	128
C4—H41···O2^iii	0.96	2.40	3.306 (8)	157
C43^i—H431···C40^i	1.16	1.70	2.538 (8)	124
N18—H181···O12	0.95	2.22	2.961 (8)	135

Symmetry codes: (i) y, x, −z+1; (ii) x−1/2, −y+1/2, −z+3/4; (iii) −y+1, −x+1, −z+1/2; (iv) y+1/2, −x+1/2, z−1/4.

(apremilastnicotinamide)

Crystal data

2(C22H24N2O7S)·C6H4N2O	Dx = 1.413 Mg m^−3
Mr = 1041.12	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 57694 reflections
a = 12.8876 (1) Å	θ = 4–68°
c = 29.4547 (2) Å	µ = 1.64 mm^−1
V = 4892.14 (8) Å^3	T = 120 K
Z = 4	Block, colorless
F(000) = 2183.989	0.32 × 0.24 × 0.16 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4359 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.039
ω scans	θmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.60, Tmax = 0.77	k = −15→15
90858 measured reflections	l = −35→35
4429 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.039	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.05P)^2 + 4.21P] , where P = (max(Fo^2,0) + 2Fc^2)/3
wR(F^2) = 0.106	(Δ/σ)max = 0.001
S = 1.02	Δρmax = 0.54 e Å^−3
4429 reflections	Δρmin = −0.47 e Å^−3
350 parameters	Absolute structure: Flack (1983), 1816 Friedel-pairs
57 restraints	Absolute structure parameter: 0.01 (2)
Primary atom site location: Other

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.40408 (5)	0.16284 (5)	0.46354 (2)	0.0286
O2	0.31159 (15)	0.21130 (15)	0.44569 (7)	0.0351
O3	0.44578 (16)	0.07561 (15)	0.43907 (7)	0.0375
C4	0.3796 (3)	0.1259 (3)	0.51985 (10)	0.0430
C5	0.5017 (2)	0.2588 (2)	0.46997 (8)	0.0270
C6	0.5461 (2)	0.2969 (2)	0.42483 (8)	0.0258
N7	0.46516 (16)	0.34458 (16)	0.39623 (7)	0.0252
C8	0.43716 (19)	0.30687 (19)	0.35368 (8)	0.0252
C9	0.3461 (2)	0.36864 (19)	0.33869 (8)	0.0253
C10	0.3231 (2)	0.43952 (19)	0.37260 (8)	0.0274
C11	0.3991 (2)	0.42444 (19)	0.40975 (8)	0.0262
O12	0.48091 (14)	0.23567 (14)	0.33384 (6)	0.0306
O13	0.40556 (15)	0.47053 (14)	0.44576 (6)	0.0317
C14	0.2906 (2)	0.36469 (19)	0.29837 (9)	0.0266
C15	0.2087 (2)	0.4351 (2)	0.29409 (9)	0.0301
C16	0.1857 (2)	0.5046 (2)	0.32857 (10)	0.0342
C17	0.2429 (2)	0.5096 (2)	0.36865 (9)	0.0312
N18	0.32153 (17)	0.29309 (17)	0.26523 (7)	0.0286
C19	0.2800 (2)	0.2761 (2)	0.22329 (9)	0.0293
C20	0.3422 (2)	0.2023 (2)	0.19433 (9)	0.0369
O21	0.20092 (15)	0.31738 (16)	0.20995 (6)	0.0364
C22	0.6385 (2)	0.3688 (2)	0.43224 (9)	0.0271
C23	0.6525 (2)	0.4236 (2)	0.47291 (9)	0.0282
C24	0.7385 (2)	0.4876 (2)	0.47889 (9)	0.0298
C25	0.8116 (2)	0.4964 (2)	0.44365 (10)	0.0315
C26	0.7968 (2)	0.4426 (2)	0.40369 (9)	0.0337
C27	0.7109 (2)	0.3789 (2)	0.39814 (9)	0.0310
O28	0.75763 (15)	0.54457 (16)	0.51723 (7)	0.0373
C29	0.6807 (2)	0.5400 (2)	0.55255 (10)	0.0384
C30	0.7104 (3)	0.6157 (3)	0.58912 (13)	0.0586
O31	0.89513 (15)	0.56018 (16)	0.45259 (7)	0.0407
C32	0.9653 (3)	0.5761 (3)	0.41558 (11)	0.0537
C34	0.5391 (6)	0.5197 (6)	0.2961 (3)	0.1355
C35	0.4586 (5)	0.5701 (5)	0.2713 (2)	0.1239
C36	0.4092 (9)	0.6550 (9)	0.2898 (4)	0.1466	0.5000
N37	0.3342 (11)	0.7152 (11)	0.2646 (5)	0.1697	0.5000
O38	0.4246 (11)	0.6777 (10)	0.3310 (5)	0.2134	0.5000
H201	0.3034	0.1814	0.1688	0.0554*
H203	0.4032	0.2340	0.1839	0.0548*
H202	0.3618	0.1424	0.2108	0.0541*
H181	0.3713	0.2549	0.2721	0.0340*
H171	0.2294	0.5590	0.3914	0.0366*
H161	0.1290	0.5518	0.3248	0.0414*
H151	0.1703	0.4375	0.2677	0.0358*
H321	1.0186	0.6239	0.4262	0.0790*
H323	0.9301	0.6065	0.3899	0.0796*
H322	0.9992	0.5101	0.4068	0.0799*
H231	0.6038	0.4163	0.4963	0.0328*
H302	0.6569	0.6183	0.6120	0.0890*
H301	0.7746	0.5948	0.6029	0.0885*
H303	0.7184	0.6817	0.5743	0.0884*
H292	0.6154	0.5614	0.5398	0.0459*
H291	0.6728	0.4689	0.5642	0.0453*
H261	0.8450	0.4474	0.3808	0.0405*
H271	0.7005	0.3426	0.3707	0.0361*
H61	0.5695	0.2369	0.4081	0.0302*
H52	0.5572	0.2254	0.4864	0.0325*
H51	0.4708	0.3160	0.4871	0.0317*
H41	0.4406	0.0953	0.5323	0.0638*
H43	0.3253	0.0755	0.5181	0.0642*
H42	0.3568	0.1848	0.5372	0.0632*
H331	0.6532	0.4020	0.3008	0.1357*	0.5000
H341	0.5546	0.5404	0.3278	0.1617*
H351	0.4258	0.6290	0.2843	0.1523*	0.5000
C33	0.5931 (5)	0.4348 (5)	0.2723 (2)	0.1247	0.5000
N133	0.5944 (5)	0.4384 (5)	0.2720 (2)	0.1295	0.5000

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0297 (3)	0.0275 (3)	0.0286 (3)	−0.0049 (2)	−0.0009 (2)	0.0020 (3)
O2	0.0292 (10)	0.0391 (11)	0.0371 (10)	−0.0027 (8)	−0.0059 (8)	0.0010 (8)
O3	0.0387 (11)	0.0296 (10)	0.0442 (11)	−0.0036 (8)	−0.0005 (9)	−0.0039 (8)
C4	0.0449 (17)	0.0479 (18)	0.0362 (15)	−0.0062 (14)	0.0029 (13)	0.0124 (13)
C5	0.0274 (13)	0.0279 (13)	0.0256 (12)	−0.0030 (10)	−0.0022 (10)	0.0018 (10)
C6	0.0273 (12)	0.0257 (12)	0.0245 (12)	0.0018 (10)	0.0011 (10)	−0.0013 (10)
N7	0.0275 (11)	0.0249 (10)	0.0232 (10)	−0.0004 (9)	0.0024 (8)	−0.0015 (8)
C8	0.0253 (12)	0.0261 (12)	0.0243 (11)	−0.0015 (10)	0.0029 (10)	0.0004 (10)
C9	0.0264 (12)	0.0230 (12)	0.0265 (12)	−0.0022 (10)	0.0051 (10)	0.0001 (9)
C10	0.0281 (13)	0.0254 (12)	0.0286 (12)	−0.0030 (10)	0.0063 (10)	−0.0017 (10)
C11	0.0286 (12)	0.0236 (12)	0.0264 (12)	−0.0022 (10)	0.0048 (10)	−0.0004 (10)
O12	0.0319 (10)	0.0315 (10)	0.0284 (9)	0.0060 (8)	0.0018 (7)	−0.0062 (8)
O13	0.0382 (10)	0.0288 (9)	0.0281 (9)	0.0002 (8)	0.0028 (8)	−0.0062 (8)
C14	0.0265 (13)	0.0247 (12)	0.0286 (13)	−0.0027 (10)	0.0031 (10)	0.0005 (10)
C15	0.0262 (13)	0.0285 (13)	0.0357 (14)	−0.0012 (10)	−0.0006 (11)	−0.0015 (11)
C16	0.0293 (14)	0.0294 (14)	0.0437 (15)	0.0066 (11)	0.0003 (12)	−0.0036 (12)
C17	0.0328 (14)	0.0263 (13)	0.0346 (14)	0.0015 (11)	0.0047 (11)	−0.0043 (11)
N18	0.0255 (11)	0.0312 (11)	0.0293 (11)	0.0057 (9)	−0.0009 (9)	−0.0053 (9)
C19	0.0299 (14)	0.0309 (13)	0.0271 (13)	−0.0029 (11)	0.0011 (10)	0.0024 (11)
C20	0.0380 (15)	0.0431 (16)	0.0295 (13)	0.0022 (13)	−0.0004 (12)	−0.0071 (12)
O21	0.0364 (10)	0.0407 (11)	0.0321 (9)	0.0063 (9)	−0.0052 (8)	0.0003 (8)
C22	0.0254 (13)	0.0262 (13)	0.0298 (13)	0.0028 (11)	0.0013 (10)	0.0007 (10)
C23	0.0261 (12)	0.0271 (13)	0.0313 (13)	−0.0013 (10)	0.0047 (10)	−0.0018 (10)
C24	0.0260 (13)	0.0280 (13)	0.0355 (13)	−0.0009 (10)	−0.0003 (10)	−0.0021 (11)
C25	0.0244 (13)	0.0282 (13)	0.0418 (14)	−0.0023 (10)	−0.0003 (11)	0.0054 (11)
C26	0.0280 (13)	0.0387 (15)	0.0345 (13)	0.0014 (11)	0.0053 (11)	0.0063 (12)
C27	0.0310 (14)	0.0329 (14)	0.0291 (13)	0.0028 (11)	0.0027 (11)	0.0015 (11)
O28	0.0308 (10)	0.0385 (11)	0.0426 (10)	−0.0064 (8)	0.0030 (8)	−0.0125 (9)
C29	0.0268 (13)	0.0472 (17)	0.0411 (14)	−0.0013 (12)	0.0016 (12)	−0.0156 (13)
C30	0.0433 (19)	0.074 (3)	0.058 (2)	−0.0110 (17)	0.0045 (16)	−0.0294 (19)
O31	0.0294 (10)	0.0447 (12)	0.0479 (12)	−0.0124 (9)	0.0021 (9)	0.0050 (9)
C32	0.0360 (17)	0.078 (3)	0.0468 (18)	−0.0207 (17)	−0.0054 (14)	0.0264 (17)
C34	0.110 (4)	0.117 (4)	0.180 (6)	−0.043 (4)	0.041 (4)	0.025 (4)
C35	0.097 (3)	0.085 (3)	0.190 (7)	−0.026 (3)	0.057 (4)	0.039 (4)
C36	0.135 (6)	0.119 (6)	0.186 (9)	−0.021 (6)	0.078 (6)	0.033 (6)
N37	0.175 (7)	0.159 (7)	0.175 (11)	−0.006 (8)	0.064 (7)	0.041 (7)
O38	0.213 (9)	0.192 (9)	0.236 (10)	−0.030 (9)	0.026 (10)	0.029 (9)
C33	0.108 (5)	0.105 (5)	0.162 (7)	−0.029 (5)	0.049 (5)	0.046 (5)
N133	0.132 (7)	0.102 (6)	0.155 (8)	0.016 (6)	0.042 (7)	0.039 (6)

Geometric parameters (Å, º)

S1—O2	1.445 (2)	C22—C27	1.377 (4)
S1—O3	1.439 (2)	C23—C24	1.393 (4)
S1—C4	1.754 (3)	C23—H231	0.937
S1—C5	1.774 (3)	C24—C25	1.406 (4)
C4—H41	0.953	C24—O28	1.370 (3)
C4—H43	0.957	C25—C26	1.379 (4)
C4—H42	0.962	C25—O31	1.380 (3)
C5—C6	1.528 (3)	C26—C27	1.389 (4)
C5—H52	0.966	C26—H261	0.919
C5—H51	0.978	C27—H271	0.944
C6—N7	1.475 (3)	O28—C29	1.439 (3)
C6—C22	1.525 (4)	C29—C30	1.503 (4)
C6—H61	0.966	C29—H292	0.961
N7—C8	1.392 (3)	C29—H291	0.984
N7—C11	1.393 (3)	C30—H302	0.964
C8—C9	1.485 (4)	C30—H301	0.960
C8—O12	1.225 (3)	C30—H303	0.962
C9—C10	1.386 (3)	O31—C32	1.431 (4)
C9—C14	1.387 (4)	C32—H321	0.974
C10—C11	1.482 (4)	C32—H323	0.965
C10—C17	1.378 (4)	C32—H322	0.990
C11—O13	1.219 (3)	C34—C35	1.425 (10)
C14—C15	1.397 (4)	C34—H341	0.991
C14—N18	1.401 (3)	C34—C33	1.474 (10)
C15—C16	1.386 (4)	C34—N133	1.452 (10)
C15—H151	0.922	C35—C35^i	1.360 (14)
C16—C17	1.393 (4)	C35—C36	1.378 (9)
C16—H161	0.958	C35—H351	0.950
C17—H171	0.942	C36—N37	1.445 (9)
N18—C19	1.364 (3)	C36—O38	1.263 (9)
N18—H181	0.834	N37—N37^i	1.24 (3)
C19—C20	1.508 (4)	H331—C33	1.217
C19—O21	1.215 (3)	H331—N133	1.229
C20—H201	0.942	C33—N133^i	1.419 (14)
C20—H203	0.938	C33—C33^i	1.410 (14)
C20—H202	0.947	N133—N133^i	1.430 (14)
C22—C23	1.402 (4)
O2—S1—O3	117.61 (12)	C23—C22—C27	119.3 (2)
O2—S1—C4	108.26 (14)	C22—C23—C24	120.5 (2)
O3—S1—C4	109.17 (14)	C22—C23—H231	119.5
O2—S1—C5	108.81 (12)	C24—C23—H231	119.9
O3—S1—C5	109.47 (12)	C23—C24—C25	119.2 (2)
C4—S1—C5	102.45 (13)	C23—C24—O28	124.4 (2)
S1—C4—H41	109.2	C25—C24—O28	116.4 (2)
S1—C4—H43	105.4	C24—C25—C26	119.8 (2)
H41—C4—H43	110.1	C24—C25—O31	115.5 (2)
S1—C4—H42	110.1	C26—C25—O31	124.8 (2)
H41—C4—H42	111.9	C25—C26—C27	120.5 (2)
H43—C4—H42	109.9	C25—C26—H261	120.0
S1—C5—C6	113.37 (17)	C27—C26—H261	119.4
S1—C5—H52	105.6	C26—C27—C22	120.7 (3)
C6—C5—H52	107.6	C26—C27—H271	120.5
S1—C5—H51	107.0	C22—C27—H271	118.8
C6—C5—H51	111.1	C24—O28—C29	116.7 (2)
H52—C5—H51	112.2	O28—C29—C30	108.4 (2)
C5—C6—N7	111.4 (2)	O28—C29—H292	108.0
C5—C6—C22	111.3 (2)	C30—C29—H292	108.4
N7—C6—C22	112.4 (2)	O28—C29—H291	111.2
C5—C6—H61	107.6	C30—C29—H291	112.3
N7—C6—H61	105.3	H292—C29—H291	108.3
C22—C6—H61	108.4	C29—C30—H302	110.0
C6—N7—C8	123.5 (2)	C29—C30—H301	109.9
C6—N7—C11	125.2 (2)	H302—C30—H301	109.3
C8—N7—C11	110.9 (2)	C29—C30—H303	106.0
N7—C8—C9	106.6 (2)	H302—C30—H303	111.4
N7—C8—O12	124.9 (2)	H301—C30—H303	110.2
C9—C8—O12	128.6 (2)	C25—O31—C32	115.6 (2)
C8—C9—C10	108.0 (2)	O31—C32—H321	106.9
C8—C9—C14	130.0 (2)	O31—C32—H323	110.9
C10—C9—C14	122.1 (2)	H321—C32—H323	109.0
C9—C10—C11	107.7 (2)	O31—C32—H322	110.8
C9—C10—C17	122.1 (2)	H321—C32—H322	108.4
C11—C10—C17	130.1 (2)	H323—C32—H322	110.6
C10—C11—N7	106.8 (2)	C35—C34—H341	120.5
C10—C11—O13	128.6 (2)	C35—C34—C33	116.0 (8)
N7—C11—O13	124.6 (2)	H341—C34—C33	123.5
C9—C14—C15	116.3 (2)	C35—C34—N133	115.9 (8)
C9—C14—N18	118.3 (2)	H341—C34—N133	123.7
C15—C14—N18	125.4 (2)	C33—C34—N133	1.779 (13)
C14—C15—C16	121.0 (3)	C34—C35—C35^i	123.1 (5)
C14—C15—H151	120.3	C34—C35—C36	119.7 (7)
C16—C15—H151	118.7	C35^i—C35—C36	117.1 (5)
C15—C16—C17	122.5 (2)	C34—C35—H351	118.8
C15—C16—H161	119.3	C35^i—C35—H351	118.0
C17—C16—H161	118.1	C36—C35—H351	1.1
C16—C17—C10	116.0 (2)	C35—C36—N37	122.1 (11)
C16—C17—H171	122.5	C35—C36—O38	119.4 (2)
C10—C17—H171	121.5	N37—C36—O38	118.3 (11)
C14—N18—C19	128.7 (2)	C36—N37—N37^i	115.0 (10)
C14—N18—H181	115.9	C33—H331—N133	2.3
C19—N18—H181	115.4	C34—C33—N133^i	119.9 (5)
N18—C19—C20	113.9 (2)	C34—C33—H331	103.4
N18—C19—O21	123.5 (2)	N133^i—C33—H331	136.4
C20—C19—O21	122.6 (2)	C34—C33—C33^i	120.8 (5)
C19—C20—H201	110.5	N133^i—C33—C33^i	2.01 (2)
C19—C20—H203	110.8	H331—C33—C33^i	135.7
H201—C20—H203	108.0	C34—N133—N133^i	120.7 (5)
C19—C20—H202	111.4	C34—N133—C33^i	121.7 (5)
H201—C20—H202	108.5	N133^i—N133—C33^i	1.98 (2)
H203—C20—H202	107.5	C34—N133—H331	104.0
C6—C22—C23	121.9 (2)	N133^i—N133—H331	134.0
C6—C22—C27	118.8 (2)	C33^i—N133—H331	133.5

Symmetry code: (i) −y+1, −x+1, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N18—H181···O12	0.83	2.32	2.975 (5)	136
C15—H151···O21	0.92	2.33	2.908 (5)	120
C32—H321···O21^ii	0.97	2.54	3.484 (5)	164
C23—H231···O13^iii	0.94	2.43	3.360 (5)	176
C26—H261···O3^iv	0.92	2.45	3.348 (5)	165
C27—H271···O2^iv	0.94	2.52	3.267 (5)	136
C5—H52···O21^iv	0.97	2.50	3.438 (5)	165
C5—H51···O13^iii	0.98	2.29	3.146 (5)	146
C4—H43···O12^v	0.96	2.42	3.042 (5)	123
C4—H42···O2^iii	0.96	2.54	3.386 (5)	147
C35—H351···N37	0.95	1.72	2.471 (5)	133
C35—H351···O38	0.95	1.51	2.281 (5)	135

Symmetry codes: (ii) −y+3/2, x+1/2, z+1/4; (iii) y, x, −z+1; (iv) x+1/2, −y+1/2, −z+3/4; (v) −y+1/2, x−1/2, z+1/4.

(apremilastniacin)

Crystal data

2(C22H24N2O7S)·C6H5NO2	Dx = 1.415 Mg m^−3
Mr = 1044.09	Cu Kα radiation, λ = 1.54184 Å
Tetragonal, P41212	Cell parameters from 42937 reflections
a = 12.9268 (1) Å	θ = 5–67°
c = 29.3204 (2) Å	µ = 1.65 mm^−1
V = 4899.50 (8) Å^3	T = 120 K
Z = 4	Block, colorless
F(000) = 2192	0.29 × 0.28 × 0.21 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4270 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.060
ω scans	θmax = 67.5°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.44, Tmax = 0.71	k = −15→15
83935 measured reflections	l = −35→34
4406 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.036	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.04P)^2 + 4.32P] , where P = (max(Fo^2,0) + 2Fc^2)/3
wR(F^2) = 0.093	(Δ/σ)max = 0.003
S = 1.00	Δρmax = 0.29 e Å^−3
4406 reflections	Δρmin = −0.31 e Å^−3
353 parameters	Absolute structure: Flack (1983), 1809 Friedel-pairs
20 restraints	Absolute structure parameter: −0.003 (19)
Primary atom site location: structure-invariant direct methods

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.59601 (5)	0.83687 (4)	0.464702 (19)	0.0259
O2	0.55379 (14)	0.92432 (13)	0.44083 (6)	0.0355
O3	0.68880 (13)	0.79027 (14)	0.44653 (6)	0.0325
C4	0.6193 (2)	0.8715 (2)	0.52176 (9)	0.0418
C5	0.49931 (18)	0.73988 (18)	0.47024 (7)	0.0247
C6	0.45581 (18)	0.70322 (18)	0.42456 (7)	0.0241
N7	0.53685 (15)	0.65596 (14)	0.39608 (6)	0.0224
C8	0.56631 (17)	0.69460 (17)	0.35336 (7)	0.0217
C9	0.65621 (18)	0.63246 (17)	0.33854 (8)	0.0227
C10	0.67799 (19)	0.55998 (18)	0.37203 (7)	0.0257
C11	0.60169 (19)	0.57523 (18)	0.40940 (8)	0.0251
O12	0.52327 (13)	0.76583 (12)	0.33374 (5)	0.0268
O13	0.59388 (14)	0.52813 (13)	0.44514 (5)	0.0305
C14	0.71201 (18)	0.63665 (18)	0.29790 (8)	0.0259
C15	0.7932 (2)	0.5662 (2)	0.29372 (9)	0.0322
C16	0.8147 (2)	0.4949 (2)	0.32790 (10)	0.0383
C17	0.7568 (2)	0.4896 (2)	0.36776 (9)	0.0331
N18	0.68222 (15)	0.70935 (15)	0.26508 (6)	0.0267
C19	0.72369 (19)	0.72518 (19)	0.22266 (8)	0.0282
C20	0.6620 (2)	0.7992 (2)	0.19363 (8)	0.0363
O21	0.80150 (14)	0.68275 (14)	0.20918 (6)	0.0344
C22	0.36378 (18)	0.63129 (18)	0.43143 (8)	0.0248
C23	0.34839 (18)	0.57601 (19)	0.47199 (8)	0.0282
C24	0.26238 (19)	0.5122 (2)	0.47731 (9)	0.0325
C25	0.19014 (19)	0.50399 (19)	0.44169 (10)	0.0326
C26	0.20607 (19)	0.55836 (19)	0.40163 (9)	0.0306
C27	0.29219 (19)	0.62181 (18)	0.39673 (8)	0.0274
O28	0.24210 (14)	0.45491 (16)	0.51564 (7)	0.0452
C29	0.3187 (2)	0.4577 (3)	0.55131 (10)	0.0453
C30	0.2882 (2)	0.3786 (3)	0.58691 (13)	0.0686
O31	0.10716 (14)	0.44038 (15)	0.44999 (7)	0.0427
C32	0.0356 (2)	0.4294 (3)	0.41309 (10)	0.0480
O40	0.5639 (6)	0.3097 (5)	0.3341 (2)	0.0953	0.5000
O41	0.6329 (5)	0.2656 (5)	0.2657 (2)	0.0894	0.5000
C42	0.5804 (6)	0.3287 (6)	0.2936 (3)	0.0665	0.5000
C43	0.5451 (2)	0.4269 (2)	0.27201 (13)	0.0722
C44	0.4688 (2)	0.4788 (2)	0.29429 (11)	0.0687
C45	0.4153 (5)	0.5564 (4)	0.2718 (3)	0.0707	0.5000
N46	0.4140 (5)	0.5576 (5)	0.2719 (3)	0.1162	0.5000
H41	0.4435	0.7692	0.4880	0.0289*
H42	0.5289	0.6817	0.4869	0.0289*
H51	0.4332	0.7642	0.4081	0.0284*
H171	0.7031	0.8208	0.1683	0.0553*
H172	0.6032	0.7648	0.1823	0.0550*
H173	0.6393	0.8599	0.2109	0.0548*
H181	0.8348	0.5654	0.2682	0.0392*
H191	0.8714	0.4505	0.3244	0.0459*
H201	0.7707	0.4411	0.3900	0.0402*
H221	0.3951	0.5848	0.4960	0.0336*
H251	0.3253	0.5300	0.5627	0.0544*
H252	0.3835	0.4367	0.5380	0.0545*
H261	0.2240	0.3971	0.5994	0.0999*
H262	0.3389	0.3777	0.6106	0.1006*
H263	0.2853	0.3128	0.5723	0.1002*
H291	0.0688	0.4002	0.3869	0.0732*
H292	0.0025	0.4975	0.4059	0.0735*
H293	−0.0163	0.3813	0.4236	0.0724*
H301	0.1584	0.5553	0.3784	0.0355*
H311	0.3021	0.6596	0.3700	0.0326*
H321	0.6468	0.8115	0.5380	0.0624*
H322	0.6680	0.9271	0.5210	0.0624*
H323	0.5561	0.8944	0.5352	0.0629*
H431	0.5793	0.3692	0.2873	0.0871*	0.5000
H441	0.4522	0.4626	0.3250	0.0828*
H451	0.3590	0.5905	0.2863	0.0806*	0.5000
H411	0.6519	0.2059	0.2827	0.1029*	0.5000
H182	0.6263	0.7533	0.2732	0.0322*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0292 (3)	0.0257 (3)	0.0227 (2)	−0.0070 (2)	0.0011 (2)	−0.0030 (2)
O2	0.0390 (10)	0.0263 (9)	0.0413 (10)	−0.0058 (8)	0.0027 (8)	0.0025 (8)
O3	0.0281 (9)	0.0383 (10)	0.0312 (9)	−0.0046 (8)	0.0039 (7)	−0.0007 (8)
C4	0.0451 (16)	0.0495 (17)	0.0310 (13)	−0.0084 (13)	−0.0013 (12)	−0.0150 (12)
C5	0.0275 (12)	0.0268 (12)	0.0198 (10)	−0.0060 (9)	0.0006 (9)	−0.0016 (9)
C6	0.0289 (12)	0.0231 (11)	0.0202 (10)	−0.0009 (10)	−0.0032 (9)	0.0029 (9)
N7	0.0285 (10)	0.0209 (9)	0.0177 (8)	0.0001 (8)	−0.0043 (7)	0.0015 (7)
C8	0.0255 (12)	0.0215 (11)	0.0182 (10)	−0.0042 (9)	−0.0050 (9)	−0.0007 (8)
C9	0.0250 (11)	0.0199 (11)	0.0231 (10)	−0.0025 (9)	−0.0068 (9)	0.0010 (9)
C10	0.0291 (12)	0.0245 (11)	0.0235 (10)	−0.0035 (9)	−0.0074 (9)	0.0036 (9)
C11	0.0308 (12)	0.0229 (11)	0.0218 (11)	−0.0014 (10)	−0.0074 (9)	0.0012 (9)
O12	0.0307 (9)	0.0264 (9)	0.0234 (7)	0.0049 (7)	−0.0026 (7)	0.0063 (7)
O13	0.0416 (10)	0.0278 (9)	0.0222 (8)	−0.0004 (8)	−0.0048 (7)	0.0069 (7)
C14	0.0265 (12)	0.0257 (12)	0.0255 (12)	−0.0025 (9)	−0.0040 (9)	0.0034 (9)
C15	0.0295 (13)	0.0325 (13)	0.0347 (13)	0.0032 (10)	0.0032 (10)	0.0076 (10)
C16	0.0325 (14)	0.0358 (15)	0.0467 (15)	0.0116 (12)	0.0022 (12)	0.0120 (12)
C17	0.0357 (14)	0.0299 (13)	0.0336 (13)	0.0049 (11)	−0.0050 (11)	0.0111 (11)
N18	0.0261 (10)	0.0293 (11)	0.0246 (10)	0.0053 (9)	−0.0004 (8)	0.0070 (8)
C19	0.0310 (13)	0.0296 (12)	0.0240 (11)	−0.0026 (10)	−0.0023 (10)	0.0022 (10)
C20	0.0386 (15)	0.0447 (16)	0.0255 (12)	0.0050 (13)	0.0015 (11)	0.0107 (11)
O21	0.0342 (10)	0.0415 (10)	0.0275 (9)	0.0072 (8)	0.0049 (7)	0.0027 (7)
C22	0.0269 (12)	0.0225 (11)	0.0250 (11)	0.0018 (10)	−0.0035 (9)	0.0004 (9)
C23	0.0260 (12)	0.0286 (12)	0.0301 (12)	−0.0044 (10)	−0.0097 (10)	0.0079 (10)
C24	0.0280 (13)	0.0274 (13)	0.0420 (14)	−0.0034 (10)	−0.0054 (11)	0.0103 (10)
C25	0.0234 (12)	0.0250 (12)	0.0493 (15)	−0.0019 (10)	−0.0070 (11)	0.0013 (11)
C26	0.0283 (13)	0.0290 (13)	0.0344 (13)	0.0023 (10)	−0.0096 (10)	−0.0046 (10)
C27	0.0295 (13)	0.0267 (12)	0.0261 (12)	0.0040 (10)	−0.0042 (10)	−0.0003 (9)
O28	0.0279 (10)	0.0492 (12)	0.0585 (12)	−0.0108 (9)	−0.0115 (9)	0.0310 (10)
C29	0.0244 (13)	0.0617 (19)	0.0499 (16)	−0.0032 (13)	−0.0048 (12)	0.0328 (15)
C30	0.0332 (17)	0.099 (3)	0.073 (2)	−0.0049 (17)	−0.0027 (16)	0.057 (2)
O31	0.0281 (10)	0.0394 (11)	0.0607 (12)	−0.0113 (8)	−0.0133 (9)	0.0078 (9)
C32	0.0269 (14)	0.068 (2)	0.0488 (16)	−0.0167 (14)	0.0055 (12)	−0.0243 (15)
O40	0.123 (6)	0.077 (4)	0.085 (4)	0.000 (4)	−0.012 (4)	−0.001 (3)
O41	0.108 (5)	0.076 (4)	0.085 (4)	0.033 (3)	−0.029 (4)	−0.009 (3)
C42	0.079 (5)	0.057 (4)	0.064 (5)	−0.005 (4)	−0.014 (4)	−0.014 (4)
C43	0.063 (2)	0.070 (2)	0.083 (2)	0.0100 (19)	−0.010 (2)	−0.018 (2)
C44	0.054 (2)	0.074 (3)	0.078 (3)	−0.0051 (19)	−0.0023 (19)	−0.012 (2)
C45	0.054 (3)	0.070 (4)	0.088 (4)	0.006 (3)	−0.017 (3)	−0.030 (3)
N46	0.105 (6)	0.120 (6)	0.124 (6)	0.017 (6)	0.000 (6)	−0.023 (6)

Geometric parameters (Å, º)

S1—O2	1.4373 (19)	C22—C27	1.381 (3)
S1—O3	1.4441 (18)	C23—C24	1.393 (3)
S1—C4	1.758 (3)	C23—H221	0.935
S1—C5	1.778 (2)	C24—C25	1.405 (4)
C4—H321	0.977	C24—O28	1.371 (3)
C4—H322	0.955	C25—C26	1.384 (4)
C4—H323	0.955	C25—O31	1.373 (3)
C5—C6	1.528 (3)	C26—C27	1.390 (4)
C5—H41	0.967	C26—H301	0.919
C5—H42	0.974	C27—H311	0.932
C6—N7	1.472 (3)	O28—C29	1.440 (3)
C6—C22	1.523 (3)	C29—C30	1.513 (4)
C6—H51	0.969	C29—H251	0.996
N7—C8	1.401 (3)	C29—H252	0.964
N7—C11	1.394 (3)	C30—H261	0.938
C8—C9	1.478 (3)	C30—H262	0.955
C8—O12	1.220 (3)	C30—H263	0.955
C9—C10	1.386 (3)	O31—C32	1.431 (3)
C9—C14	1.394 (3)	C32—H291	0.957
C10—C11	1.487 (3)	C32—H292	1.001
C10—C17	1.371 (3)	C32—H293	0.964
C11—O13	1.216 (3)	O40—C42	1.230 (10)
C14—C15	1.395 (3)	O41—C42	1.340 (9)
C14—N18	1.399 (3)	O41—H411	0.950
C15—C16	1.390 (4)	C42—C43	1.490 (9)
C15—H181	0.922	C42—H431	0.555
C16—C17	1.389 (4)	C43—C43^i	1.389 (8)
C16—H191	0.937	C43—C44	1.359 (5)
C17—H201	0.923	C43—H431	0.976
N18—C19	1.370 (3)	C44—C45	1.386 (8)
N18—H182	0.950	C44—N46	1.405 (8)
C19—C20	1.509 (3)	C44—H441	0.950
C19—O21	1.212 (3)	C45—N46^i	1.382 (9)
C20—H171	0.956	C45—C45^i	1.380 (17)
C20—H172	0.940	C45—H451	0.950
C20—H173	0.979	N46—N46^i	1.384 (19)
C22—C23	1.402 (3)	N46—H451	0.929
O2—S1—O3	117.63 (11)	C22—C23—H221	119.1
O2—S1—C4	109.18 (13)	C24—C23—H221	120.2
O3—S1—C4	108.36 (13)	C23—C24—C25	119.5 (2)
O2—S1—C5	109.40 (11)	C23—C24—O28	124.3 (2)
O3—S1—C5	108.88 (11)	C25—C24—O28	116.2 (2)
C4—S1—C5	102.30 (12)	C24—C25—C26	119.6 (2)
S1—C4—H321	108.9	C24—C25—O31	115.6 (2)
S1—C4—H322	106.4	C26—C25—O31	124.8 (2)
H321—C4—H322	111.7	C25—C26—C27	120.4 (2)
S1—C4—H323	109.0	C25—C26—H301	120.4
H321—C4—H323	110.9	C27—C26—H301	119.1
H322—C4—H323	109.8	C26—C27—C22	120.8 (2)
S1—C5—C6	113.42 (15)	C26—C27—H311	120.4
S1—C5—H41	107.3	C22—C27—H311	118.7
C6—C5—H41	108.6	C24—O28—C29	116.75 (19)
S1—C5—H42	108.3	O28—C29—C30	107.8 (2)
C6—C5—H42	110.1	O28—C29—H251	109.0
H41—C5—H42	109.0	C30—C29—H251	115.1
C5—C6—N7	111.34 (19)	O28—C29—H252	107.2
C5—C6—C22	111.15 (18)	C30—C29—H252	108.4
N7—C6—C22	112.18 (18)	H251—C29—H252	109.0
C5—C6—H51	107.2	C29—C30—H261	109.1
N7—C6—H51	105.7	C29—C30—H262	109.4
C22—C6—H51	109.0	H261—C30—H262	109.1
C6—N7—C8	123.53 (18)	C29—C30—H263	107.6
C6—N7—C11	125.42 (18)	H261—C30—H263	111.5
C8—N7—C11	110.71 (19)	H262—C30—H263	110.1
N7—C8—C9	106.43 (19)	C25—O31—C32	115.5 (2)
N7—C8—O12	124.5 (2)	O31—C32—H291	110.8
C9—C8—O12	129.1 (2)	O31—C32—H292	110.3
C8—C9—C10	108.6 (2)	H291—C32—H292	111.7
C8—C9—C14	129.6 (2)	O31—C32—H293	105.8
C10—C9—C14	121.8 (2)	H291—C32—H293	108.4
C9—C10—C11	107.3 (2)	H292—C32—H293	109.7
C9—C10—C17	122.3 (2)	C42—O41—H411	107.8
C11—C10—C17	130.4 (2)	O41—C42—O40	123.8 (8)
C10—C11—N7	106.96 (18)	O41—C42—C43	114.5 (6)
C10—C11—O13	128.6 (2)	O40—C42—C43	121.8 (7)
N7—C11—O13	124.5 (2)	O41—C42—H431	112.5
C9—C14—C15	116.1 (2)	O40—C42—H431	120.4
C9—C14—N18	118.1 (2)	C43—C42—H431	17.8
C15—C14—N18	125.8 (2)	C42—C43—C43^i	122.5 (4)
C14—C15—C16	121.3 (2)	C42—C43—C44	116.0 (4)
C14—C15—H181	121.2	C43^i—C43—C44	120.5 (2)
C16—C15—H181	117.5	C42—C43—H431	10.0
C15—C16—C17	122.1 (2)	C43^i—C43—H431	120.5
C15—C16—H191	119.0	C44—C43—H431	119.0
C17—C16—H191	118.9	C43—C44—C45	119.4 (4)
C16—C17—C10	116.4 (2)	C43—C44—N46	120.0 (4)
C16—C17—H201	121.5	C45—C44—N46	0.5 (7)
C10—C17—H201	122.1	C43—C44—H441	120.7
C14—N18—C19	128.1 (2)	C45—C44—H441	119.8
C14—N18—H182	116.0	N46—C44—H441	119.3
C19—N18—H182	115.9	C44—C45—N46^i	121.0 (9)
N18—C19—C20	113.6 (2)	C44—C45—C45^i	120.0 (4)
N18—C19—O21	123.6 (2)	N46^i—C45—C45^i	0.9 (6)
C20—C19—O21	122.8 (2)	C44—C45—H451	120.4
C19—C20—H171	109.3	N46^i—C45—H451	118.6
C19—C20—H172	109.0	C45^i—C45—H451	119.6
H171—C20—H172	108.1	C44—N46—N46^i	119.5 (4)
C19—C20—H173	112.0	C44—N46—C45^i	118.5 (9)
H171—C20—H173	109.6	N46^i—N46—C45^i	0.9 (6)
H172—C20—H173	108.7	C44—N46—H451	120.4
C6—C22—C23	122.3 (2)	N46^i—N46—H451	120.1
C6—C22—C27	118.7 (2)	C45^i—N46—H451	121.1
C23—C22—C27	119.0 (2)	C43—H431—C42	152.2
C22—C23—C24	120.7 (2)	C45—H451—N46	0.6

Symmetry code: (i) −y+1, −x+1, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H41···O21^ii	0.97	2.48	3.438 (4)	170
C5—H42···O13	0.97	2.48	3.087 (4)	120
C5—H42···O13^iii	0.97	2.29	3.140 (4)	145
C23—H221···O13^iii	0.94	2.44	3.370 (4)	174
C26—H301···O2^ii	0.92	2.45	3.358 (4)	168
C27—H311···O3^ii	0.93	2.52	3.249 (4)	135
C4—H321···O3^iii	0.98	2.48	3.365 (4)	150
C4—H322···O12^iv	0.96	2.38	3.059 (4)	128
C43—H431···O40	0.98	1.58	2.380 (4)	135
C43—H431···O41	0.98	1.64	2.381 (4)	130
O41—H411···O31^v	0.95	2.04	2.865 (4)	144
N18—H182···O12	0.95	2.22	2.968 (4)	134

Symmetry codes: (ii) x−1/2, −y+3/2, −z+3/4; (iii) y, x, −z+1; (iv) −y+3/2, x+1/2, z+1/4; (v) x+1/2, −y+1/2, −z+3/4.

(Apremilast_paraxylene)

Crystal data

C26H30.50N2O7S	Dx = 1.377 Mg m^−3
Mr = 515.10	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 65234 reflections
a = 13.1850 (1) Å	θ = 4–68°
c = 28.5930 (1) Å	µ = 1.58 mm^−1
V = 4970.73 (8) Å^3	T = 120 K
Z = 8	Plate, colorless
F(000) = 2180	0.28 × 0.23 × 0.11 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4440 reflections with I > 2.0σ(I)
Focussing mirrors monochromator	Rint = 0.031
ω scans	θmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro (Rigaku Oxford Diffraction, 2017)	h = −15→15
Tmin = 0.46, Tmax = 0.84	k = −15→15
97817 measured reflections	l = −34→34
4498 independent reflections

Refinement

Refinement on F^2	H-atom parameters constrained
Least-squares matrix: full	Method, part 1, Chebychev polynomial, (Watkin, 1994, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)^2]^2 Ai are: 971. 0.155E + 04 843. 281.
R[F^2 > 2σ(F^2)] = 0.027	(Δ/σ)max = 0.001
wR(F^2) = 0.060	Δρmax = 0.32 e Å^−3
S = 0.93	Δρmin = −0.78 e Å^−3
4498 reflections	Extinction correction: Larson (1970), Equation 22
333 parameters	Extinction coefficient: 46 (3)
46 restraints	Absolute structure: Parsons, Flack & Wagner (2013), 1844 Friedel Pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.001 (2)
Hydrogen site location: difference Fourier map

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.41595 (4)	0.17294 (4)	0.464742 (16)	0.0220
O2	0.32619 (11)	0.21876 (11)	0.44496 (5)	0.0281
O3	0.45695 (11)	0.08485 (11)	0.44171 (5)	0.0318
C4	0.39237 (17)	0.14366 (18)	0.52390 (7)	0.0337
C5	0.51135 (14)	0.26710 (14)	0.46951 (6)	0.0209
C6	0.55298 (14)	0.30413 (14)	0.42271 (6)	0.0197
N7	0.47209 (12)	0.35062 (12)	0.39377 (5)	0.0191
C8	0.40838 (14)	0.42905 (14)	0.40826 (6)	0.0195
C9	0.33061 (14)	0.44164 (14)	0.37099 (6)	0.0195
C10	0.35046 (14)	0.36987 (13)	0.33659 (6)	0.0181
C11	0.44020 (14)	0.31037 (14)	0.35103 (6)	0.0183
O12	0.41718 (11)	0.47532 (10)	0.44476 (4)	0.0248
O13	0.48095 (10)	0.24026 (10)	0.33065 (4)	0.0233
C14	0.25166 (15)	0.50996 (15)	0.36725 (7)	0.0234
C15	0.19221 (15)	0.50244 (15)	0.32708 (7)	0.0252
C16	0.21127 (14)	0.43152 (14)	0.29206 (7)	0.0227
C17	0.29236 (14)	0.36289 (14)	0.29639 (6)	0.0191
N18	0.31978 (12)	0.28975 (12)	0.26321 (5)	0.0210
C19	0.27730 (15)	0.27130 (15)	0.22021 (6)	0.0228
C20	0.33594 (16)	0.19658 (16)	0.19115 (7)	0.0283
O21	0.19965 (11)	0.31228 (11)	0.20653 (4)	0.0277
C22	0.64330 (14)	0.37427 (14)	0.42984 (6)	0.0203
C23	0.65628 (14)	0.42961 (14)	0.47124 (6)	0.0212
C24	0.74127 (15)	0.49010 (15)	0.47779 (6)	0.0219
C25	0.81534 (14)	0.49611 (15)	0.44246 (7)	0.0235
C26	0.80205 (15)	0.44154 (16)	0.40148 (7)	0.0252
C27	0.71625 (15)	0.38078 (15)	0.39541 (7)	0.0239
O28	0.75978 (11)	0.54603 (11)	0.51735 (5)	0.0271
C29	0.68238 (16)	0.54356 (17)	0.55291 (7)	0.0284
C30	0.7125 (2)	0.6155 (2)	0.59124 (9)	0.0474
O31	0.89741 (11)	0.55618 (12)	0.45196 (5)	0.0319
C32	0.96898 (17)	0.5685 (2)	0.41495 (8)	0.0393
C34	0.3908 (2)	0.6092 (2)	0.2500	0.0850
C35	0.4557 (2)	0.5997 (2)	0.28672 (11)	0.0652
C36	0.5292 (2)	0.5258 (2)	0.28705 (9)	0.0515
C37	0.53975 (17)	0.46025 (17)	0.2500	0.0445
C38	0.6194 (2)	0.3806 (2)	0.2500	0.1108
H43	0.4573	0.1288	0.5387	0.0507*
H42	0.3579	0.2017	0.5388	0.0504*
H52	0.5665	0.2380	0.4871	0.0244*
H51	0.4832	0.3238	0.4872	0.0237*
H61	0.5763	0.2432	0.4050	0.0220*
H141	0.2386	0.5606	0.3911	0.0266*
H151	0.1378	0.5478	0.3225	0.0296*
H161	0.1687	0.4302	0.2650	0.0267*
H201	0.2954	0.1732	0.1651	0.0425*
H202	0.3973	0.2292	0.1791	0.0431*
H203	0.3558	0.1380	0.2094	0.0432*
H231	0.6065	0.4259	0.4943	0.0245*
H261	0.8508	0.4447	0.3770	0.0294*
H271	0.7075	0.3417	0.3668	0.0277*
H291	0.6762	0.4733	0.5655	0.0340*
H292	0.6163	0.5644	0.5395	0.0349*
H303	0.6626	0.6144	0.6163	0.0717*
H302	0.7807	0.6011	0.6032	0.0704*
H301	0.7169	0.6864	0.5776	0.0701*
H323	1.0239	0.6144	0.4265	0.0576*
H322	0.9983	0.5037	0.4052	0.0586*
H321	0.9359	0.6012	0.3878	0.0570*
H181	0.3720	0.2553	0.2704	0.0230*
H41	0.3492	0.0854	0.5244	0.0493*
C33	0.3106 (3)	0.6894 (3)	0.2500	0.1633
H351	0.4497	0.6486	0.3125	0.0827*
H361	0.5734	0.5215	0.3128	0.0655*
H381	0.6357	0.3399	0.2201	0.1638*	0.5000
H382	0.6940	0.4003	0.2574	0.1643*	0.5000
H383	0.6164	0.3205	0.2732	0.1630*	0.5000
H331	0.2723	0.6850	0.2219	0.1903*
H332	0.3416	0.7543	0.2520	0.1903*
H333	0.2670	0.6798	0.2761	0.1903*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0216 (2)	0.0229 (2)	0.0215 (2)	−0.00309 (18)	−0.00278 (19)	0.00168 (18)
O2	0.0228 (7)	0.0350 (8)	0.0264 (7)	−0.0023 (6)	−0.0043 (6)	0.0042 (6)
O3	0.0335 (8)	0.0260 (7)	0.0359 (8)	−0.0025 (6)	−0.0031 (7)	−0.0064 (7)
C4	0.0342 (12)	0.0398 (13)	0.0270 (11)	−0.0060 (10)	−0.0018 (9)	0.0094 (9)
C5	0.0221 (9)	0.0215 (10)	0.0189 (9)	−0.0018 (7)	−0.0026 (7)	−0.0013 (7)
C6	0.0195 (9)	0.0222 (9)	0.0174 (8)	0.0034 (7)	0.0000 (7)	−0.0012 (7)
N7	0.0205 (8)	0.0209 (8)	0.0158 (7)	0.0012 (6)	−0.0003 (6)	−0.0018 (6)
C8	0.0213 (9)	0.0183 (9)	0.0188 (9)	−0.0023 (7)	0.0044 (8)	0.0006 (7)
C9	0.0213 (9)	0.0187 (9)	0.0186 (8)	−0.0032 (7)	0.0034 (7)	−0.0001 (7)
C10	0.0181 (9)	0.0172 (9)	0.0189 (9)	−0.0029 (7)	0.0027 (7)	0.0016 (7)
C11	0.0188 (9)	0.0195 (9)	0.0165 (8)	−0.0024 (7)	0.0029 (7)	0.0003 (7)
O12	0.0304 (7)	0.0245 (7)	0.0196 (6)	0.0002 (6)	0.0012 (6)	−0.0061 (6)
O13	0.0250 (7)	0.0243 (7)	0.0206 (6)	0.0036 (5)	0.0003 (5)	−0.0056 (6)
C14	0.0249 (10)	0.0223 (10)	0.0230 (9)	0.0003 (8)	0.0044 (8)	−0.0017 (8)
C15	0.0225 (10)	0.0242 (10)	0.0289 (10)	0.0035 (8)	0.0025 (8)	0.0007 (8)
C16	0.0214 (9)	0.0244 (10)	0.0224 (9)	0.0004 (8)	−0.0011 (8)	0.0009 (8)
C17	0.0213 (9)	0.0191 (9)	0.0170 (9)	−0.0028 (7)	0.0022 (7)	0.0009 (7)
N18	0.0218 (8)	0.0226 (8)	0.0185 (7)	0.0018 (7)	−0.0007 (6)	−0.0034 (6)
C19	0.0261 (10)	0.0243 (10)	0.0180 (9)	−0.0062 (8)	0.0018 (8)	0.0003 (8)
C20	0.0324 (11)	0.0312 (11)	0.0213 (9)	0.0007 (9)	0.0018 (9)	−0.0056 (8)
O21	0.0276 (8)	0.0353 (8)	0.0203 (7)	0.0014 (6)	−0.0049 (6)	−0.0017 (6)
C22	0.0198 (9)	0.0212 (9)	0.0200 (9)	0.0025 (7)	−0.0004 (7)	0.0013 (7)
C23	0.0212 (9)	0.0221 (10)	0.0202 (9)	−0.0001 (7)	0.0027 (7)	−0.0012 (7)
C24	0.0227 (10)	0.0224 (10)	0.0205 (9)	0.0013 (7)	−0.0013 (8)	−0.0003 (7)
C25	0.0183 (9)	0.0252 (10)	0.0269 (10)	−0.0017 (7)	−0.0013 (8)	0.0041 (8)
C26	0.0223 (10)	0.0306 (11)	0.0227 (9)	0.0016 (8)	0.0029 (8)	0.0025 (8)
C27	0.0236 (10)	0.0295 (10)	0.0188 (9)	0.0030 (8)	0.0007 (7)	0.0000 (8)
O28	0.0265 (7)	0.0293 (8)	0.0255 (7)	−0.0071 (6)	0.0019 (6)	−0.0075 (6)
C29	0.0244 (10)	0.0349 (11)	0.0260 (10)	−0.0006 (9)	0.0012 (8)	−0.0088 (9)
C30	0.0453 (15)	0.0599 (17)	0.0370 (13)	−0.0101 (13)	0.0052 (11)	−0.0229 (12)
O31	0.0234 (7)	0.0403 (9)	0.0320 (8)	−0.0113 (6)	0.0020 (6)	0.0016 (7)
C32	0.0242 (11)	0.0619 (16)	0.0318 (11)	−0.0134 (11)	−0.0017 (9)	0.0165 (11)
C34	0.0468 (15)	0.0468 (15)	0.161 (4)	0.0130 (19)	0.053 (2)	0.053 (2)
C35	0.079 (2)	0.0336 (14)	0.082 (2)	−0.0176 (14)	0.0505 (17)	−0.0126 (14)
C36	0.0479 (14)	0.0625 (16)	0.0443 (13)	−0.0272 (13)	0.0059 (12)	0.0104 (13)
C37	0.0325 (10)	0.0325 (10)	0.068 (2)	0.0063 (14)	0.0238 (12)	0.0238 (12)
C38	0.076 (2)	0.076 (2)	0.181 (5)	0.049 (3)	0.083 (3)	0.083 (3)
C33	0.088 (3)	0.088 (3)	0.314 (8)	0.049 (3)	0.105 (4)	0.105 (4)

Geometric parameters (Å, º)

S1—O2	1.4442 (14)	C23—H231	0.932
S1—O3	1.4404 (15)	C24—C25	1.407 (3)
S1—C4	1.763 (2)	C24—O28	1.372 (2)
S1—C5	1.7726 (18)	C25—C26	1.386 (3)
C4—H43	0.975	C25—O31	1.368 (2)
C4—H42	0.987	C26—C27	1.397 (3)
C4—H41	0.956	C26—H261	0.952
C5—C6	1.527 (2)	C27—H271	0.973
C5—H52	0.964	O28—C29	1.441 (2)
C5—H51	0.975	C29—C30	1.503 (3)
C6—N7	1.483 (2)	C29—H291	0.997
C6—C22	1.521 (3)	C29—H292	0.991
C6—H61	0.998	C30—H303	0.973
N7—C8	1.395 (2)	C30—H302	0.980
N7—C11	1.397 (2)	C30—H301	1.013
C8—C9	1.488 (3)	O31—C32	1.427 (3)
C8—O12	1.214 (2)	C32—H323	0.999
C9—C10	1.390 (3)	C32—H322	0.979
C9—C14	1.381 (3)	C32—H321	0.990
C10—C11	1.478 (2)	C34—C35^i	1.360 (4)
C10—C17	1.385 (3)	C34—C35	1.360 (4)
C11—O13	1.218 (2)	C34—C33	1.496 (6)
C14—C15	1.394 (3)	C35—C36	1.374 (4)
C14—H141	0.970	C35—H351	0.982
C15—C16	1.393 (3)	C36—C37	1.375 (3)
C15—H151	0.943	C36—H361	0.940
C16—C17	1.406 (3)	C37—C38	1.485 (5)
C16—H161	0.956	C38—H382^i	1.039
C17—N18	1.400 (2)	C38—H383^i	1.035
N18—C19	1.373 (2)	C38—H381^i	1.032
N18—H181	0.850	C38—H381	1.032
C19—C20	1.503 (3)	C38—H382	1.039
C19—O21	1.222 (2)	C38—H383	1.035
C20—H201	0.967	C33—H333^i	0.950
C20—H202	0.978	C33—H332^i	0.950
C20—H203	0.969	C33—H331^i	0.950
C22—C23	1.401 (3)	C33—H331	0.950
C22—C27	1.379 (3)	C33—H332	0.950
C23—C24	1.388 (3)	C33—H333	0.950
O2—S1—O3	117.76 (9)	C26—C27—C22	120.78 (18)
O2—S1—C4	108.84 (10)	C26—C27—H271	120.3
O3—S1—C4	109.17 (11)	C22—C27—H271	118.9
O2—S1—C5	108.58 (9)	C24—O28—C29	116.34 (15)
O3—S1—C5	109.49 (9)	O28—C29—C30	108.25 (17)
C4—S1—C5	101.81 (9)	O28—C29—H291	109.4
S1—C4—H43	107.8	C30—C29—H291	110.2
S1—C4—H42	109.0	O28—C29—H292	110.0
H43—C4—H42	111.9	C30—C29—H292	109.9
S1—C4—H41	107.2	H291—C29—H292	109.0
H43—C4—H41	110.8	C29—C30—H303	110.5
H42—C4—H41	110.0	C29—C30—H302	111.9
S1—C5—C6	114.31 (13)	H303—C30—H302	111.1
S1—C5—H52	107.3	C29—C30—H301	108.5
C6—C5—H52	108.2	H303—C30—H301	109.6
S1—C5—H51	107.9	H302—C30—H301	105.1
C6—C5—H51	110.3	C25—O31—C32	116.23 (17)
H52—C5—H51	108.7	O31—C32—H323	107.7
C5—C6—N7	111.28 (15)	O31—C32—H322	111.9
C5—C6—C22	111.01 (15)	H323—C32—H322	109.7
N7—C6—C22	112.74 (15)	O31—C32—H321	109.9
C5—C6—H61	107.4	H323—C32—H321	108.4
N7—C6—H61	105.7	H322—C32—H321	109.2
C22—C6—H61	108.4	C35^i—C34—C35	118.8 (4)
C6—N7—C8	125.01 (14)	C35^i—C34—C33	120.62 (18)
C6—N7—C11	123.22 (15)	C35—C34—C33	120.62 (18)
C8—N7—C11	111.10 (15)	C34—C35—C36	120.9 (3)
N7—C8—C9	106.55 (14)	C34—C35—H351	117.9
N7—C8—O12	124.75 (18)	C36—C35—H351	121.2
C9—C8—O12	128.70 (18)	C35—C36—C37	120.8 (2)
C8—C9—C10	107.52 (16)	C35—C36—H361	119.1
C8—C9—C14	130.37 (17)	C37—C36—H361	120.1
C10—C9—C14	122.10 (18)	C36^i—C37—C36	117.8 (3)
C9—C10—C11	108.32 (16)	C36^i—C37—C38	121.11 (16)
C9—C10—C17	121.91 (17)	C36—C37—C38	121.11 (16)
C11—C10—C17	129.75 (17)	H382^i—C38—C37	119.5
C10—C11—N7	106.48 (15)	H382^i—C38—H383^i	95.6
C10—C11—O13	128.48 (17)	C37—C38—H383^i	121.0
N7—C11—O13	125.04 (17)	H382^i—C38—H381^i	95.8
C9—C14—C15	116.18 (18)	C37—C38—H381^i	121.0
C9—C14—H141	121.9	H383^i—C38—H381^i	98.1
C15—C14—H141	121.9	H382^i—C38—H381	52.5
C14—C15—C16	122.59 (18)	C37—C38—H381	121.0
C14—C15—H151	119.8	H383^i—C38—H381	47.8
C16—C15—H151	117.6	H381^i—C38—H381	118.1
C15—C16—C17	120.40 (18)	H382^i—C38—H382	121.0
C15—C16—H161	119.2	C37—C38—H382	119.5
C17—C16—H161	120.4	H383^i—C38—H382	52.8
C16—C17—C10	116.81 (17)	H381^i—C38—H382	52.5
C16—C17—N18	125.45 (17)	H381—C38—H382	95.8
C10—C17—N18	117.73 (17)	H382^i—C38—H383	52.8
C17—N18—C19	128.57 (17)	C37—C38—H383	121.0
C17—N18—H181	114.4	H383^i—C38—H383	118.1
C19—N18—H181	116.9	H381^i—C38—H383	47.8
N18—C19—C20	113.67 (17)	H381—C38—H383	98.1
N18—C19—O21	123.38 (18)	H382—C38—H383	95.6
C20—C19—O21	122.95 (17)	C34—C33—H333^i	109.5
C19—C20—H201	110.5	C34—C33—H332^i	109.5
C19—C20—H202	109.3	H333^i—C33—H332^i	109.5
H201—C20—H202	109.0	C34—C33—H331^i	109.5
C19—C20—H203	111.3	H333^i—C33—H331^i	109.5
H201—C20—H203	108.1	H332^i—C33—H331^i	109.5
H202—C20—H203	108.5	C34—C33—H331	109.5
C6—C22—C23	121.69 (16)	H333^i—C33—H331	56.2
C6—C22—C27	119.22 (17)	H332^i—C33—H331	56.2
C23—C22—C27	119.05 (18)	H331^i—C33—H331	141.1
C22—C23—C24	120.79 (17)	C34—C33—H332	109.5
C22—C23—H231	119.0	H333^i—C33—H332	56.3
C24—C23—H231	120.2	H332^i—C33—H332	141.1
C23—C24—C25	119.72 (17)	H331^i—C33—H332	56.2
C23—C24—O28	124.30 (17)	H331—C33—H332	109.5
C25—C24—O28	115.98 (17)	C34—C33—H333	109.5
C24—C25—C26	119.33 (17)	H333^i—C33—H333	141.1
C24—C25—O31	116.04 (17)	H332^i—C33—H333	56.3
C26—C25—O31	124.63 (18)	H331^i—C33—H333	56.2
C25—C26—C27	120.33 (18)	H331—C33—H333	109.5
C25—C26—H261	120.9	H332—C33—H333	109.5
C27—C26—H261	118.7

Symmetry code: (i) −y+1, −x+1, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C4—H42···O2^ii	0.99	2.50	3.439 (3)	158
C5—H52···O21^iii	0.96	2.47	3.425 (3)	169
C5—H51···O12^ii	0.98	2.30	3.186 (3)	150
C23—H231···O12^ii	0.93	2.46	3.390 (3)	180
C26—H261···O3^iii	0.95	2.44	3.375 (3)	166
C27—H271···O2^iii	0.97	2.49	3.240 (3)	134
C32—H323···O21^iv	1.00	2.58	3.566 (3)	168
N18—H181···O13	0.85	2.25	2.943 (3)	139
C4—H41···O13^v	0.96	2.42	3.208 (3)	139
C38—H381···O2^vi	1.03	2.55	3.410 (3)	140

Symmetry codes: (ii) y, x, −z+1; (iii) x+1/2, −y+1/2, −z+3/4; (iv) −y+3/2, x+1/2, z+1/4; (v) −y+1/2, x−1/2, z+1/4; (vi) y+1/2, −x+1/2, z−1/4.

(apremilastsalycilic)

Crystal data

2(C22H24N2O7S)·C7H5O3	Dx = 1.436 Mg m^−3
Mr = 1058.13	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 72094 reflections
a = 12.9133 (1) Å	θ = 3–68°
c = 29.3418 (1) Å	µ = 1.67 mm^−1
V = 4892.84 (8) Å^3	T = 120 K
Z = 4	Block, colorless
F(000) = 2220	0.68 × 0.39 × 0.36 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4398 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.027
ω scans	θmax = 67.6°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.39, Tmax = 0.55	k = −15→15
93647 measured reflections	l = −35→34
4419 independent reflections

Refinement

Refinement on F^2	H-atom parameters constrained
Least-squares matrix: full	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.03P)^2 + 2.76P] , where P = (max(Fo^2,0) + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.030	(Δ/σ)max = 0.001
wR(F^2) = 0.076	Δρmax = 0.44 e Å^−3
S = 1.09	Δρmin = −0.40 e Å^−3
4419 reflections	Extinction correction: Larson (1970), Equation 22
354 parameters	Extinction coefficient: 63 (8)
1 restraint	Absolute structure: Flack (1983), 1814 Friedel-pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.028 (15)
Hydrogen site location: difference Fourier map

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.59471 (4)	0.83550 (4)	0.465138 (15)	0.0242
O2	0.55171 (11)	0.92326 (11)	0.44146 (5)	0.0340
O3	0.68726 (11)	0.78879 (11)	0.44645 (5)	0.0310
C4	0.62007 (18)	0.87021 (18)	0.52192 (7)	0.0389
C5	0.49789 (14)	0.73890 (14)	0.47098 (6)	0.0224
C6	0.45306 (14)	0.70281 (14)	0.42521 (6)	0.0213
N7	0.53400 (12)	0.65588 (12)	0.39636 (5)	0.0207
C8	0.56265 (14)	0.69524 (14)	0.35381 (6)	0.0204
C9	0.65200 (14)	0.63294 (14)	0.33836 (6)	0.0216
C10	0.67405 (15)	0.55974 (15)	0.37176 (6)	0.0250
C11	0.59820 (15)	0.57410 (14)	0.40918 (6)	0.0236
O12	0.51982 (10)	0.76676 (10)	0.33449 (4)	0.0253
O13	0.59024 (11)	0.52582 (10)	0.44459 (4)	0.0289
C14	0.70797 (15)	0.63807 (14)	0.29797 (6)	0.0235
C15	0.78966 (16)	0.56738 (16)	0.29312 (7)	0.0307
C16	0.81141 (17)	0.49541 (17)	0.32723 (8)	0.0369
C17	0.75325 (16)	0.48928 (17)	0.36721 (7)	0.0331
N18	0.67843 (12)	0.71109 (12)	0.26532 (5)	0.0244
C19	0.71945 (15)	0.72760 (15)	0.22300 (6)	0.0264
C20	0.65841 (17)	0.80243 (17)	0.19426 (7)	0.0342
O21	0.79725 (11)	0.68414 (11)	0.20920 (5)	0.0329
C22	0.36090 (14)	0.63116 (14)	0.43198 (6)	0.0226
C23	0.34596 (14)	0.57445 (15)	0.47212 (6)	0.0259
C24	0.25982 (15)	0.51068 (15)	0.47698 (7)	0.0295
C25	0.18764 (15)	0.50373 (15)	0.44125 (7)	0.0291
C26	0.20275 (15)	0.55945 (15)	0.40171 (7)	0.0274
C27	0.28941 (15)	0.62329 (15)	0.39718 (6)	0.0255
O28	0.23942 (11)	0.45088 (13)	0.51442 (5)	0.0420
C29	0.31609 (16)	0.45051 (19)	0.55017 (7)	0.0385
C30	0.28629 (19)	0.3685 (2)	0.58428 (10)	0.0579
O31	0.10442 (11)	0.43955 (11)	0.44928 (5)	0.0371
C32	0.03223 (16)	0.4294 (2)	0.41256 (8)	0.0408
O33	0.6391 (3)	0.2618 (3)	0.26068 (13)	0.0534	0.5000
O34	0.5646 (3)	0.3009 (3)	0.32644 (13)	0.0576	0.5000
C35	0.5850 (4)	0.3231 (4)	0.28769 (17)	0.0439	0.5000
C36	0.5500 (2)	0.4212 (2)	0.27206 (13)	0.0672
C37	0.4725 (2)	0.4762 (2)	0.29097 (11)	0.0682
O38	0.4409 (3)	0.4530 (3)	0.33436 (11)	0.0619	0.5000
C39	0.4187 (2)	0.5552 (2)	0.27152 (11)	0.0725
H51	0.4428	0.7688	0.4898	0.0270*
H52	0.5307	0.6809	0.4877	0.0269*
H61	0.4307	0.7625	0.4079	0.0241*
H151	0.8310	0.5701	0.2670	0.0357*
H161	0.8693	0.4501	0.3226	0.0436*
H171	0.7665	0.4390	0.3889	0.0403*
H203	0.7001	0.8246	0.1691	0.0507*
H201	0.6371	0.8623	0.2126	0.0508*
H202	0.5966	0.7679	0.1826	0.0517*
H231	0.3951	0.5809	0.4967	0.0306*
H261	0.1566	0.5555	0.3778	0.0326*
H271	0.2997	0.6620	0.3700	0.0300*
H292	0.3205	0.5195	0.5652	0.0452*
H291	0.3818	0.4335	0.5357	0.0450*
H301	0.3412	0.3612	0.6067	0.0866*
H302	0.2236	0.3880	0.6000	0.0867*
H303	0.2782	0.3051	0.5680	0.0868*
H322	−0.0206	0.3802	0.4231	0.0598*
H323	0.0008	0.4997	0.4052	0.0615*
H321	0.0660	0.4003	0.3862	0.0605*
H391	0.3632	0.5904	0.2873	0.0864*
H181	0.6282	0.7494	0.2732	0.0286*
H41	0.6464	0.8092	0.5382	0.0575*
H43	0.6724	0.9227	0.5205	0.0574*
H42	0.5588	0.8968	0.5348	0.0575*
H331	0.6559	0.2021	0.2692	0.0803*	0.5000
H361	0.5734	0.3556	0.2825	0.0807*	0.5000
H371	0.4505	0.4601	0.3211	0.0835*	0.5000

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0265 (2)	0.0249 (2)	0.0213 (2)	−0.00683 (18)	0.00231 (18)	−0.00325 (18)
O2	0.0377 (8)	0.0261 (7)	0.0381 (8)	−0.0055 (6)	0.0026 (6)	0.0039 (6)
O3	0.0260 (7)	0.0381 (8)	0.0290 (7)	−0.0046 (6)	0.0059 (6)	−0.0031 (6)
C4	0.0425 (13)	0.0452 (13)	0.0291 (10)	−0.0099 (10)	−0.0007 (9)	−0.0148 (9)
C5	0.0242 (9)	0.0241 (9)	0.0189 (8)	−0.0059 (7)	0.0022 (7)	−0.0012 (7)
C6	0.0248 (9)	0.0209 (9)	0.0184 (8)	0.0005 (7)	−0.0014 (7)	0.0004 (7)
N7	0.0252 (8)	0.0203 (7)	0.0166 (7)	−0.0008 (6)	−0.0026 (6)	0.0016 (6)
C8	0.0229 (9)	0.0204 (9)	0.0177 (8)	−0.0038 (7)	−0.0031 (7)	0.0000 (7)
C9	0.0222 (9)	0.0198 (9)	0.0227 (8)	−0.0019 (7)	−0.0039 (7)	0.0002 (7)
C10	0.0271 (10)	0.0231 (9)	0.0247 (9)	−0.0008 (8)	−0.0038 (8)	0.0040 (7)
C11	0.0279 (9)	0.0211 (9)	0.0219 (9)	−0.0010 (8)	−0.0060 (8)	0.0015 (7)
O12	0.0277 (7)	0.0262 (7)	0.0219 (6)	0.0036 (5)	−0.0019 (5)	0.0055 (5)
O13	0.0371 (8)	0.0264 (7)	0.0232 (7)	0.0003 (6)	−0.0035 (6)	0.0065 (6)
C14	0.0249 (9)	0.0223 (9)	0.0233 (9)	−0.0019 (7)	−0.0028 (7)	0.0018 (7)
C15	0.0292 (10)	0.0304 (11)	0.0326 (10)	0.0041 (8)	0.0050 (8)	0.0062 (8)
C16	0.0319 (11)	0.0334 (11)	0.0454 (12)	0.0126 (9)	0.0072 (10)	0.0115 (10)
C17	0.0331 (11)	0.0297 (11)	0.0365 (11)	0.0077 (9)	−0.0014 (9)	0.0115 (9)
N18	0.0241 (8)	0.0260 (8)	0.0231 (8)	0.0048 (6)	0.0006 (6)	0.0037 (6)
C19	0.0288 (10)	0.0271 (10)	0.0232 (9)	−0.0027 (8)	−0.0013 (8)	−0.0003 (8)
C20	0.0362 (11)	0.0410 (12)	0.0253 (10)	0.0035 (10)	0.0002 (9)	0.0090 (9)
O21	0.0333 (8)	0.0391 (8)	0.0263 (7)	0.0075 (6)	0.0059 (6)	0.0012 (6)
C22	0.0245 (9)	0.0204 (9)	0.0228 (9)	0.0005 (7)	−0.0028 (7)	−0.0015 (7)
C23	0.0240 (9)	0.0262 (10)	0.0276 (9)	−0.0031 (8)	−0.0099 (8)	0.0047 (8)
C24	0.0273 (10)	0.0253 (10)	0.0358 (10)	−0.0032 (7)	−0.0076 (8)	0.0093 (8)
C25	0.0222 (10)	0.0217 (9)	0.0433 (11)	−0.0028 (8)	−0.0074 (9)	−0.0006 (8)
C26	0.0263 (10)	0.0270 (10)	0.0288 (9)	0.0030 (8)	−0.0090 (8)	−0.0050 (8)
C27	0.0266 (10)	0.0263 (10)	0.0236 (9)	0.0034 (7)	−0.0041 (8)	−0.0009 (7)
O28	0.0282 (8)	0.0469 (9)	0.0510 (9)	−0.0154 (7)	−0.0157 (7)	0.0284 (8)
C29	0.0228 (10)	0.0530 (13)	0.0398 (11)	−0.0066 (9)	−0.0079 (9)	0.0245 (11)
C30	0.0334 (13)	0.077 (2)	0.0636 (16)	−0.0135 (12)	−0.0120 (12)	0.0453 (15)
O31	0.0260 (7)	0.0358 (8)	0.0494 (9)	−0.0112 (6)	−0.0133 (7)	0.0061 (7)
C32	0.0229 (10)	0.0621 (16)	0.0376 (12)	−0.0114 (10)	0.0008 (9)	−0.0190 (11)
O33	0.051 (2)	0.0397 (19)	0.070 (2)	0.0168 (16)	−0.0177 (18)	−0.0093 (17)
O34	0.071 (3)	0.046 (2)	0.055 (2)	−0.0022 (19)	−0.013 (2)	−0.0026 (17)
C35	0.043 (3)	0.041 (3)	0.048 (3)	0.002 (2)	−0.013 (2)	−0.002 (2)
C36	0.0390 (14)	0.0343 (14)	0.128 (3)	0.0002 (11)	0.0095 (16)	0.0086 (15)
C37	0.0383 (14)	0.0467 (16)	0.120 (3)	−0.0083 (12)	−0.0144 (17)	−0.0276 (17)
O38	0.055 (2)	0.057 (2)	0.074 (3)	−0.0097 (19)	0.005 (2)	−0.015 (2)
C39	0.0490 (16)	0.0611 (18)	0.107 (2)	0.0156 (14)	−0.0346 (18)	−0.0437 (19)

Geometric parameters (Å, º)

S1—O2	1.4406 (15)	C20—H202	0.975
S1—O3	1.4466 (15)	C22—C23	1.400 (3)
S1—C4	1.756 (2)	C22—C27	1.380 (3)
S1—C5	1.7743 (18)	C23—C24	1.391 (3)
C4—H41	0.982	C23—H231	0.964
C4—H43	0.957	C24—C25	1.406 (3)
C4—H42	0.942	C24—O28	1.368 (2)
C5—C6	1.535 (2)	C25—C26	1.379 (3)
C5—H51	0.980	C25—O31	1.377 (2)
C5—H52	0.990	C26—C27	1.396 (3)
C6—N7	1.475 (2)	C26—H261	0.922
C6—C22	1.520 (3)	C27—H271	0.951
C6—H61	0.966	O28—C29	1.442 (2)
N7—C8	1.398 (2)	C29—C30	1.508 (3)
N7—C11	1.394 (2)	C29—H292	0.997
C8—C9	1.478 (3)	C29—H291	0.973
C8—O12	1.217 (2)	C30—H301	0.971
C9—C10	1.391 (3)	C30—H302	0.965
C9—C14	1.390 (3)	C30—H303	0.952
C10—C11	1.483 (3)	O31—C32	1.431 (2)
C10—C17	1.375 (3)	C32—H322	0.982
C11—O13	1.216 (2)	C32—H323	1.018
C14—C15	1.402 (3)	C32—H321	0.964
C14—N18	1.397 (2)	O33—C35	1.320 (6)
C15—C16	1.394 (3)	O33—H331	0.839
C15—H151	0.934	O34—C35	1.202 (6)
C16—C17	1.395 (3)	C35—C36	1.421 (5)
C16—H161	0.958	C36—C36^i	1.398 (7)
C17—H171	0.925	C36—C37	1.347 (4)
N18—C19	1.367 (2)	C36—H361	0.950
N18—H181	0.848	C37—O38	1.3700 (1)
C19—C20	1.505 (3)	C37—C39	1.359 (4)
C19—O21	1.220 (2)	C37—H371	0.950
C20—H203	0.957	C39—C39^i	1.350 (7)
C20—H201	0.981	C39—H391	0.967
O2—S1—O3	117.63 (8)	C19—C20—H202	109.3
O2—S1—C4	109.18 (11)	H203—C20—H202	109.1
O3—S1—C4	108.17 (10)	H201—C20—H202	108.8
O2—S1—C5	109.15 (9)	C6—C22—C23	122.41 (16)
O3—S1—C5	109.01 (9)	C6—C22—C27	118.14 (16)
C4—S1—C5	102.66 (9)	C23—C22—C27	119.45 (17)
S1—C4—H41	108.7	C22—C23—C24	120.39 (17)
S1—C4—H43	105.7	C22—C23—H231	119.6
H41—C4—H43	110.2	C24—C23—H231	120.0
S1—C4—H42	108.5	C23—C24—C25	119.44 (18)
H41—C4—H42	112.9	C23—C24—O28	124.76 (17)
H43—C4—H42	110.6	C25—C24—O28	115.79 (17)
S1—C5—C6	113.25 (12)	C24—C25—C26	120.02 (18)
S1—C5—H51	106.8	C24—C25—O31	115.36 (18)
C6—C5—H51	109.8	C26—C25—O31	124.62 (18)
S1—C5—H52	106.1	C25—C26—C27	120.10 (17)
C6—C5—H52	111.4	C25—C26—H261	121.4
H51—C5—H52	109.3	C27—C26—H261	118.5
C5—C6—N7	111.07 (15)	C26—C27—C22	120.60 (18)
C5—C6—C22	111.45 (14)	C26—C27—H271	120.2
N7—C6—C22	112.31 (14)	C22—C27—H271	119.2
C5—C6—H61	109.3	C24—O28—C29	116.97 (15)
N7—C6—H61	103.7	O28—C29—C30	108.05 (18)
C22—C6—H61	108.7	O28—C29—H292	111.0
C6—N7—C8	123.42 (15)	C30—C29—H292	110.4
C6—N7—C11	125.29 (14)	O28—C29—H291	106.4
C8—N7—C11	111.03 (15)	C30—C29—H291	110.7
N7—C8—C9	106.43 (15)	H292—C29—H291	110.2
N7—C8—O12	124.88 (17)	C29—C30—H301	109.3
C9—C8—O12	128.70 (16)	C29—C30—H302	110.3
C8—C9—C10	108.27 (16)	H301—C30—H302	108.4
C8—C9—C14	129.92 (16)	C29—C30—H303	107.4
C10—C9—C14	121.79 (17)	H301—C30—H303	109.6
C9—C10—C11	107.54 (16)	H302—C30—H303	111.8
C9—C10—C17	122.23 (18)	C25—O31—C32	115.78 (17)
C11—C10—C17	130.22 (17)	O31—C32—H322	105.9
C10—C11—N7	106.73 (14)	O31—C32—H323	109.7
C10—C11—O13	128.63 (17)	H322—C32—H323	111.5
N7—C11—O13	124.64 (18)	O31—C32—H321	110.2
C9—C14—C15	116.54 (17)	H322—C32—H321	108.4
C9—C14—N18	118.35 (16)	H323—C32—H321	111.0
C15—C14—N18	125.11 (17)	C35—O33—H331	120.5
C14—C15—C16	120.83 (19)	O33—C35—O34	122.8 (5)
C14—C15—H151	119.3	O33—C35—C36	120.6 (4)
C16—C15—H151	119.9	O34—C35—C36	116.6 (5)
C15—C16—C17	122.20 (19)	C35—C36—C36^i	116.8 (3)
C15—C16—H161	117.6	C35—C36—C37	125.0 (4)
C17—C16—H161	120.2	C36^i—C36—C37	116.1 (2)
C16—C17—C10	116.38 (18)	C35—C36—H361	0.1
C16—C17—H171	121.3	C36^i—C36—H361	116.7
C10—C17—H171	122.3	C37—C36—H361	125.1
C14—N18—C19	128.49 (17)	C36—C37—O38	119.3 (3)
C14—N18—H181	114.5	C36—C37—C39	127.0 (3)
C19—N18—H181	117.0	O38—C37—C39	113.7 (3)
N18—C19—C20	113.96 (17)	C36—C37—H371	119.3
N18—C19—O21	123.29 (18)	O38—C37—H371	0.0
C20—C19—O21	122.73 (17)	C39—C37—H371	113.7
C19—C20—H203	109.2	C37—C39—C39^i	116.9 (2)
C19—C20—H201	110.2	C37—C39—H391	122.1
H203—C20—H201	110.1	C39^i—C39—H391	121.0

Symmetry code: (i) −y+1, −x+1, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H51···O21^ii	0.98	2.48	3.449 (3)	171
C5—H52···O13^iii	0.99	2.31	3.155 (3)	143
C15—H151···O21	0.93	2.29	2.889 (3)	122
C23—H231···O13^iii	0.96	2.42	3.378 (3)	176
C26—H261···O2^ii	0.92	2.46	3.366 (3)	168
C27—H271···O3^ii	0.95	2.51	3.252 (3)	135
C30—H301···O38^iii	0.97	2.48	3.348 (3)	149
C32—H322···O21^iv	0.98	2.59	3.548 (3)	164
N18—H181···O12	0.85	2.29	2.972 (3)	138
C4—H41···O3^iii	0.98	2.46	3.345 (3)	149
C4—H43···O12^v	0.96	2.39	3.040 (3)	125
O33—H331···O28^vi	0.84	2.46	3.125 (3)	137
O33—H331···O31^vi	0.84	2.15	2.888 (3)	146
C36—H361···O33	0.95	1.61	2.381 (3)	135
C36—H361···O34	0.95	1.48	2.234 (3)	133

Symmetry codes: (ii) x−1/2, −y+3/2, −z+3/4; (iii) y, x, −z+1; (iv) −y+1/2, x−1/2, z+1/4; (v) −y+3/2, x+1/2, z+1/4; (vi) x+1/2, −y+1/2, −z+3/4.

(Apremilasttrifluorotoluene)

Crystal data

2(C22H24N2O7S)·C7H6F3	Dx = 1.426 Mg m^−3
Mr = 1068.10	Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212	Cell parameters from 66089 reflections
a = 12.9492 (1) Å	θ = 4–68°
c = 29.6806 (3) Å	µ = 1.69 mm^−1
V = 4976.90 (9) Å^3	T = 120 K
Z = 4	Block, colorless
F(000) = 2230	0.32 × 0.19 × 0.18 mm

Data collection

Oxford Diffraction SuperNova diffractometer	4478 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.047
ω scans	θmax = 67.6°, θmin = 3.7°
Absorption correction: multi-scan CrysAlisPro, (Agilent, 2011)	h = −15→15
Tmin = 0.51, Tmax = 0.74	k = −15→15
119531 measured reflections	l = −35→35
4502 independent reflections

Refinement

Refinement on F^2	H-atom parameters constrained
Least-squares matrix: full	Method = Modified Sheldrick w = 1/[σ^2(F^2) + ( 0.03P)^2 + 26.72P] , where P = (max(Fo^2,0) + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.067	(Δ/σ)max = 0.003
wR(F^2) = 0.161	Δρmax = 0.38 e Å^−3
S = 0.97	Δρmin = −0.57 e Å^−3
4502 reflections	Extinction correction: Larson (1970), Equation 22
381 parameters	Extinction coefficient: 108 (11)
185 restraints	Absolute structure: Flack (1983), 1849 Friedel-pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.06 (4)
Hydrogen site location: difference Fourier map

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems open-flow nitrogen cryostat (Cosier & Glazer, 1986) with a nominal stability of 0.1K.

Cosier, J. & Glazer, A.M., 1986. J. Appl. Cryst. 105-107.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C37	0.9791 (6)	0.9485 (7)	0.4782 (3)	0.0617	0.5000
C38	1.0539 (7)	1.0244 (8)	0.4854 (4)	0.0637	0.5000
C39	1.0562 (8)	1.0768 (7)	0.5262 (4)	0.0597	0.5000
C40	0.9853 (9)	1.0546 (8)	0.5587 (3)	0.0660	0.5000
C41	0.9099 (8)	0.9796 (9)	0.5514 (4)	0.0694	0.5000
C42	0.9075 (7)	0.9264 (7)	0.5121 (3)	0.0651	0.5000
F33	1.0101 (7)	0.9478 (6)	0.3999 (3)	0.0748	0.5000
F34	1.0418 (7)	0.8081 (7)	0.4376 (3)	0.0752	0.5000
F35	0.8850 (7)	0.8492 (7)	0.4247 (3)	0.0821	0.5000
C36	0.9771 (9)	0.8901 (9)	0.4353 (4)	0.0695	0.5000
S1	0.39738 (9)	0.15974 (9)	0.46439 (4)	0.0261
O2	0.3033 (3)	0.2056 (3)	0.44744 (11)	0.0329
O3	0.4402 (3)	0.0728 (3)	0.44005 (11)	0.0338
C4	0.3765 (4)	0.1236 (5)	0.52049 (16)	0.0393
C5	0.4934 (4)	0.2569 (4)	0.46954 (15)	0.0255
C6	0.5370 (4)	0.2941 (4)	0.42440 (14)	0.0262
N7	0.4555 (3)	0.3400 (3)	0.39637 (12)	0.0252
C8	0.3900 (4)	0.4206 (4)	0.40942 (15)	0.0279
C9	0.3137 (4)	0.4356 (4)	0.37257 (15)	0.0273
C10	0.3380 (4)	0.3653 (4)	0.33854 (15)	0.0242
C11	0.4273 (4)	0.3045 (4)	0.35353 (15)	0.0249
O12	0.3974 (3)	0.4677 (3)	0.44518 (11)	0.0341
O13	0.4727 (3)	0.2355 (3)	0.33353 (10)	0.0284
C14	0.2837 (4)	0.3624 (4)	0.29877 (15)	0.0256
C15	0.2012 (4)	0.4332 (4)	0.29410 (17)	0.0325
C16	0.1789 (4)	0.5010 (4)	0.32904 (18)	0.0333
C17	0.2332 (4)	0.5043 (4)	0.36898 (18)	0.0340
N18	0.3148 (3)	0.2920 (3)	0.26587 (13)	0.0305
C19	0.2704 (5)	0.2731 (5)	0.22433 (17)	0.0395
O20	0.1906 (3)	0.3125 (4)	0.21209 (12)	0.0568
C21	0.3325 (5)	0.2014 (5)	0.19577 (17)	0.0412
C22	0.6291 (4)	0.3660 (4)	0.43069 (15)	0.0252
C23	0.6452 (4)	0.4207 (4)	0.47100 (16)	0.0312
C24	0.7330 (4)	0.4819 (4)	0.47622 (16)	0.0331
C25	0.8046 (4)	0.4906 (4)	0.44060 (17)	0.0308
C26	0.7882 (4)	0.4364 (4)	0.40095 (16)	0.0291
C27	0.6996 (4)	0.3738 (4)	0.39660 (16)	0.0276
O28	0.7547 (3)	0.5396 (3)	0.51373 (12)	0.0436
C29	0.6781 (4)	0.5425 (5)	0.54841 (17)	0.0446
C30	0.7110 (5)	0.6272 (6)	0.5809 (2)	0.0693
O31	0.8882 (3)	0.5517 (3)	0.44873 (12)	0.0371
C32	0.9596 (4)	0.5633 (5)	0.41213 (17)	0.0385
H43	0.4316	0.0806	0.5317	0.0570*
H42	0.3662	0.1811	0.5401	0.0572*
H52	0.5506	0.2271	0.4871	0.0281*
H51	0.4628	0.3148	0.4855	0.0280*
H61	0.5631	0.2321	0.4082	0.0292*
H151	0.1639	0.4350	0.2676	0.0350*
H161	0.1240	0.5462	0.3253	0.0389*
H171	0.2147	0.5499	0.3919	0.0381*
H231	0.5971	0.4161	0.4943	0.0339*
H261	0.8352	0.4415	0.3771	0.0320*
H271	0.6896	0.3365	0.3696	0.0310*
H291	0.6771	0.4775	0.5649	0.0542*
H292	0.6115	0.5582	0.5364	0.0543*
H301	0.6721	0.6244	0.6089	0.0930*
H302	0.7838	0.6204	0.5884	0.0931*
H303	0.7012	0.6948	0.5676	0.0931*
H322	1.0142	0.6096	0.4212	0.0560*
H323	0.9889	0.4973	0.4042	0.0558*
H321	0.9256	0.5921	0.3863	0.0560*
H41	0.3135	0.0820	0.5216	0.0569*
H381	1.1025	1.0398	0.4624	0.0771*	0.5000
H391	1.1072	1.1282	0.5313	0.0720*	0.5000
H401	0.9874	1.0910	0.5864	0.0805*	0.5000
H411	0.8605	0.9659	0.5742	0.0833*	0.5000
H421	0.8570	0.8742	0.5078	0.0801*
H211	0.2988	0.1913	0.1677	0.0489*
H212	0.3989	0.2304	0.1908	0.0489*
H213	0.3395	0.1369	0.2107	0.0489*
H181	0.3638	0.2506	0.2736	0.0346*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C37	0.062 (4)	0.057 (4)	0.066 (4)	0.028 (4)	−0.020 (3)	0.017 (3)
C38	0.059 (4)	0.056 (4)	0.076 (5)	0.025 (4)	−0.018 (4)	0.019 (4)
C39	0.050 (5)	0.050 (5)	0.079 (6)	0.022 (5)	−0.018 (4)	0.017 (4)
C40	0.057 (4)	0.067 (4)	0.074 (4)	0.028 (4)	−0.019 (4)	0.018 (4)
C41	0.064 (4)	0.072 (4)	0.072 (4)	0.026 (4)	−0.011 (4)	0.023 (4)
C42	0.063 (4)	0.063 (4)	0.069 (5)	0.024 (4)	−0.015 (4)	0.021 (4)
F33	0.088 (4)	0.063 (4)	0.073 (4)	0.029 (4)	−0.013 (4)	0.014 (3)
F34	0.088 (5)	0.065 (4)	0.073 (4)	0.034 (4)	−0.033 (4)	0.000 (4)
F35	0.084 (5)	0.073 (5)	0.089 (5)	0.018 (4)	−0.038 (4)	−0.007 (4)
C36	0.074 (4)	0.062 (4)	0.072 (4)	0.025 (4)	−0.023 (4)	0.012 (4)
S1	0.0303 (6)	0.0306 (6)	0.0175 (5)	−0.0051 (5)	−0.0002 (5)	0.0012 (5)
O2	0.0292 (18)	0.041 (2)	0.0281 (17)	−0.0023 (16)	−0.0023 (15)	0.0042 (16)
O3	0.041 (2)	0.0326 (19)	0.0273 (17)	−0.0029 (16)	−0.0017 (15)	−0.0025 (15)
C4	0.040 (3)	0.049 (3)	0.029 (3)	−0.008 (2)	0.004 (2)	0.014 (2)
C5	0.023 (2)	0.032 (3)	0.022 (2)	−0.0033 (18)	−0.0006 (19)	−0.0057 (19)
C6	0.033 (3)	0.027 (2)	0.019 (2)	−0.002 (2)	0.003 (2)	−0.0026 (19)
N7	0.028 (2)	0.030 (2)	0.0179 (17)	−0.0041 (17)	0.0016 (15)	−0.0023 (16)
C8	0.033 (3)	0.032 (3)	0.018 (2)	−0.002 (2)	0.008 (2)	−0.0029 (19)
C9	0.031 (3)	0.027 (2)	0.025 (2)	−0.004 (2)	0.004 (2)	−0.0040 (19)
C10	0.025 (2)	0.024 (2)	0.024 (2)	−0.0013 (19)	0.0077 (19)	−0.0006 (18)
C11	0.030 (2)	0.028 (2)	0.017 (2)	−0.006 (2)	0.0051 (18)	0.0017 (18)
O12	0.044 (2)	0.035 (2)	0.0233 (17)	−0.0041 (17)	0.0046 (16)	−0.0078 (15)
O13	0.0330 (19)	0.0302 (19)	0.0220 (15)	0.0083 (14)	0.0021 (14)	−0.0011 (14)
C14	0.030 (3)	0.026 (2)	0.021 (2)	−0.0073 (19)	0.0072 (19)	0.0000 (18)
C15	0.032 (3)	0.035 (3)	0.030 (3)	0.000 (2)	−0.003 (2)	0.002 (2)
C16	0.026 (3)	0.026 (3)	0.048 (3)	0.009 (2)	0.003 (2)	0.000 (2)
C17	0.037 (3)	0.026 (3)	0.040 (3)	0.002 (2)	0.008 (2)	−0.006 (2)
N18	0.033 (2)	0.035 (2)	0.024 (2)	0.0084 (19)	0.0001 (17)	−0.0031 (18)
C19	0.045 (3)	0.050 (3)	0.024 (2)	0.013 (3)	0.003 (2)	0.001 (2)
O20	0.051 (3)	0.092 (3)	0.0274 (19)	0.032 (2)	−0.0096 (19)	−0.012 (2)
C21	0.048 (3)	0.053 (4)	0.023 (2)	0.014 (3)	0.004 (2)	−0.007 (2)
C22	0.027 (3)	0.029 (3)	0.020 (2)	0.000 (2)	−0.0017 (18)	−0.0014 (18)
C23	0.031 (3)	0.036 (3)	0.026 (2)	−0.010 (2)	0.007 (2)	−0.012 (2)
C24	0.032 (3)	0.040 (3)	0.027 (2)	−0.008 (2)	0.006 (2)	−0.009 (2)
C25	0.034 (3)	0.030 (3)	0.028 (2)	−0.006 (2)	0.008 (2)	0.002 (2)
C26	0.031 (3)	0.031 (3)	0.025 (2)	−0.002 (2)	0.008 (2)	0.002 (2)
C27	0.030 (3)	0.033 (3)	0.021 (2)	0.002 (2)	0.0008 (19)	−0.0028 (19)
O28	0.041 (2)	0.057 (3)	0.0328 (19)	−0.0182 (19)	0.0123 (17)	−0.0210 (18)
C29	0.039 (3)	0.065 (4)	0.030 (3)	−0.011 (3)	0.011 (2)	−0.021 (3)
C30	0.051 (4)	0.096 (6)	0.060 (4)	−0.019 (4)	0.016 (3)	−0.051 (4)
O31	0.0290 (19)	0.046 (2)	0.0363 (19)	−0.0152 (16)	0.0053 (15)	−0.0057 (17)
C32	0.036 (3)	0.045 (3)	0.034 (3)	−0.010 (3)	0.009 (2)	0.005 (2)

Geometric parameters (Å, º)

C37—C40^i	1.542 (13)	C6—H61	0.995
C37—C37^i	1.413 (16)	N7—C8	1.399 (6)
C37—C38^i	1.837 (14)	N7—C11	1.401 (6)
C37—C41^i	1.008 (14)	C8—C9	1.487 (7)
C37—C42^i	0.911 (10)	C8—O12	1.228 (6)
C37—C38	1.396 (12)	C9—C10	1.396 (6)
C37—C42	1.398 (5)	C9—C17	1.374 (7)
C37—C36	1.481 (13)	C10—C11	1.468 (7)
C38—C40^i	1.402 (18)	C10—C14	1.375 (7)
C38—C38^i	1.02 (2)	C11—O13	1.223 (6)
C38—C39	1.389 (12)	C14—C15	1.415 (7)
C38—H381	0.950	C14—N18	1.396 (6)
C39—C39^i	1.60 (3)	C15—C16	1.390 (7)
C39—C40	1.360 (13)	C15—H151	0.922
C39—H391	0.950	C16—C17	1.379 (8)
C40—H381^i	1.129	C16—H161	0.927
C40—F33^i	1.443 (14)	C17—H171	0.932
C40—C36^i	1.60 (2)	N18—C19	1.382 (6)
C40—C41	1.394 (13)	N18—H181	0.862
C40—H401	0.950	C19—O20	1.209 (7)
C41—F33^i	1.578 (16)	C19—C21	1.493 (7)
C41—F34^i	1.580 (12)	C21—H211	0.950
C41—F35^i	1.620 (14)	C21—H212	0.950
C41—C42	1.354 (13)	C21—H213	0.950
C41—H411	0.950	C22—C23	1.406 (6)
C42—H421^i	1.159	C22—C27	1.367 (7)
C42—C36^i	1.709 (18)	C23—C24	1.394 (7)
C42—C42^i	0.798 (19)	C23—H231	0.933
C42—H421	0.950	C24—C25	1.410 (7)
F33—H401^i	1.234	C24—O28	1.370 (6)
F33—C36	1.358 (8)	C25—C26	1.386 (7)
F34—H411^i	1.246	C25—O31	1.363 (6)
F34—C36	1.355 (12)	C26—C27	1.411 (7)
F35—H411^i	1.058	C26—H261	0.937
F35—C36	1.342 (16)	C27—H271	0.945
S1—O2	1.446 (4)	O28—C29	1.429 (6)
S1—O3	1.448 (4)	C29—C30	1.521 (8)
S1—C4	1.750 (5)	C29—H291	0.974
S1—C5	1.775 (5)	C29—H292	0.955
C4—H43	0.965	C30—H301	0.972
C4—H42	0.955	C30—H302	0.973
C4—H41	0.979	C30—H303	0.970
C5—C6	1.531 (6)	O31—C32	1.434 (6)
C5—H52	0.985	C32—H322	0.965
C5—H51	0.972	C32—H323	0.965
C6—N7	1.470 (6)	C32—H321	0.959
C6—C22	1.525 (6)	H421—H421^i	0.558
C40^i—C37—C37^i	137.8 (6)	H411^i—F35—C41^i	34.0
C40^i—C37—C38^i	89.1 (6)	H411^i—F35—C36	19.7
C37^i—C37—C38^i	48.8 (5)	C41^i—F35—C36	15.0 (7)
C40^i—C37—C41^i	62.2 (9)	C37—C36—C40^i	59.9 (6)
C37^i—C37—C41^i	159.8 (10)	C37—C36—F33	112.2 (9)
C38^i—C37—C41^i	151.3 (11)	C40^i—C36—F33	57.7 (7)
C40^i—C37—C42^i	151.6 (13)	C37—C36—F34	110.1 (8)
C37^i—C37—C42^i	70.2 (10)	C40^i—C36—F34	102.1 (9)
C38^i—C37—C42^i	119.0 (13)	F33—C36—F34	106.1 (9)
C41^i—C37—C42^i	89.6 (12)	C37—C36—F35	114.7 (8)
C40^i—C37—C38	56.7 (8)	C40^i—C36—F35	152.6 (8)
C37^i—C37—C38	81.7 (4)	F33—C36—F35	108.4 (10)
C38^i—C37—C38	33.4 (7)	F34—C36—F35	104.6 (10)
C41^i—C37—C38	118.5 (11)	C37—C36—C42^i	32.2 (3)
C42^i—C37—C38	151.6 (11)	C40^i—C36—C42^i	92.0 (9)
C40^i—C37—C42	173.7 (8)	F33—C36—C42^i	139.0 (10)
C37^i—C37—C42	37.8 (4)	F34—C36—C42^i	107.0 (7)
C38^i—C37—C42	86.5 (7)	F35—C36—C42^i	85.7 (8)
C41^i—C37—C42	122.0 (12)	O2—S1—O3	117.9 (2)
C42^i—C37—C42	32.5 (10)	O2—S1—C4	108.1 (2)
C40^i—C37—C36	63.9 (8)	O3—S1—C4	109.0 (3)
C37^i—C37—C36	158.0 (4)	O2—S1—C5	109.2 (2)
C38^i—C37—C36	153.0 (7)	O3—S1—C5	109.0 (2)
C41^i—C37—C36	1.7 (11)	C4—S1—C5	102.4 (2)
C42^i—C37—C36	87.8 (10)	S1—C4—H43	111.7
C38—C37—C42	119.5 (5)	S1—C4—H42	113.2
C38—C37—C36	120.3 (4)	H43—C4—H42	110.0
C42—C37—C36	120.2 (4)	S1—C4—H41	107.9
C40^i—C38—C37	66.9 (8)	H43—C4—H41	106.7
C40^i—C38—C37^i	116.0 (8)	H42—C4—H41	107.0
C37—C38—C37^i	49.5 (5)	S1—C5—C6	113.9 (3)
C40^i—C38—C38^i	158.3 (11)	S1—C5—H52	107.1
C37—C38—C38^i	97.7 (4)	C6—C5—H52	107.9
C37^i—C38—C38^i	48.9 (5)	S1—C5—H51	107.7
C40^i—C38—C39	171.7 (9)	C6—C5—H51	109.6
C37—C38—C39	119.5 (4)	H52—C5—H51	110.6
C37^i—C38—C39	70.0 (5)	C5—C6—N7	111.0 (4)
C38^i—C38—C39	23.8 (5)	C5—C6—C22	111.9 (4)
C40^i—C38—H381	53.2	N7—C6—C22	112.6 (4)
C37—C38—H381	119.8	C5—C6—H61	107.1
C37^i—C38—H381	169.3	N7—C6—H61	107.3
C38^i—C38—H381	141.2	C22—C6—H61	106.6
C39—C38—H381	120.6	C6—N7—C8	125.5 (4)
C39^i—C39—C38	22.2 (4)	C6—N7—C11	124.6 (4)
C39^i—C39—C40	139.9 (5)	C8—N7—C11	109.8 (4)
C38—C39—C40	120.0 (4)	N7—C8—C9	107.3 (4)
C39^i—C39—H391	98.9	N7—C8—O12	124.3 (5)
C38—C39—H391	119.7	C9—C8—O12	128.5 (5)
C40—C39—H391	120.3	C8—C9—C10	107.2 (4)
C37^i—C40—H381^i	98.6	C8—C9—C17	130.2 (4)
C37^i—C40—F33^i	104.3 (9)	C10—C9—C17	122.5 (5)
H381^i—C40—F33^i	154.5	C9—C10—C11	108.0 (4)
C37^i—C40—C36^i	56.2 (7)	C9—C10—C14	121.6 (4)
H381^i—C40—C36^i	152.7	C11—C10—C14	130.4 (4)
F33^i—C40—C36^i	52.7 (6)	C10—C11—N7	107.7 (4)
C37^i—C40—C38^i	56.4 (6)	C10—C11—O13	128.6 (4)
H381^i—C40—C38^i	42.4	N7—C11—O13	123.7 (4)
F33^i—C40—C38^i	156.1 (9)	C10—C14—C15	116.9 (4)
C36^i—C40—C38^i	112.2 (9)	C10—C14—N18	118.1 (4)
C37^i—C40—C39	80.9 (6)	C15—C14—N18	125.0 (4)
H381^i—C40—C39	21.6	C14—C15—C16	119.6 (5)
F33^i—C40—C39	156.2 (8)	C14—C15—H151	119.7
C36^i—C40—C39	137.0 (8)	C16—C15—H151	120.7
C38^i—C40—C39	25.6 (4)	C15—C16—C17	123.7 (5)
C37^i—C40—C41	39.8 (5)	C15—C16—H161	118.0
H381^i—C40—C41	137.3	C17—C16—H161	118.3
F33^i—C40—C41	67.6 (8)	C16—C17—C9	115.7 (5)
C36^i—C40—C41	16.4 (7)	C16—C17—H171	121.0
C38^i—C40—C41	95.9 (6)	C9—C17—H171	123.3
C37^i—C40—H401	159.7	C14—N18—C19	128.3 (4)
H381^i—C40—H401	101.0	C14—N18—H181	115.6
F33^i—C40—H401	57.8	C19—N18—H181	115.8
C36^i—C40—H401	103.6	N18—C19—O20	123.3 (5)
C38^i—C40—H401	143.4	N18—C19—C21	113.1 (5)
C39—C40—C41	120.6 (4)	O20—C19—C21	123.6 (5)
C39—C40—H401	119.4	C19—C21—H211	109.7
C41—C40—H401	120.0	C19—C21—H212	109.2
F33^i—C41—F34^i	86.7 (7)	H211—C21—H212	109.5
F33^i—C41—F35^i	86.4 (7)	C19—C21—H213	109.5
F34^i—C41—F35^i	83.6 (7)	H211—C21—H213	109.5
F33^i—C41—C40	57.7 (7)	H212—C21—H213	109.5
F34^i—C41—C40	101.4 (9)	C6—C22—C23	121.9 (4)
F35^i—C41—C40	143.0 (9)	C6—C22—C27	118.5 (4)
F33^i—C41—C37^i	130.1 (12)	C23—C22—C27	119.6 (4)
F34^i—C41—C37^i	126.6 (9)	C22—C23—C24	120.1 (4)
F35^i—C41—C37^i	128.1 (13)	C22—C23—H231	120.0
C40—C41—C37^i	78.1 (8)	C24—C23—H231	119.9
F33^i—C41—C42	157.5 (8)	C23—C24—C25	119.8 (4)
F34^i—C41—C42	114.7 (9)	C23—C24—O28	124.6 (4)
F35^i—C41—C42	89.0 (8)	C25—C24—O28	115.6 (4)
C40—C41—C42	120.3 (4)	C24—C25—C26	119.7 (5)
C37^i—C41—C42	42.3 (7)	C24—C25—O31	115.8 (4)
F33^i—C41—H411	66.5	C26—C25—O31	124.4 (4)
F34^i—C41—H411	52.0	C25—C26—C27	119.5 (4)
F35^i—C41—H411	38.5	C25—C26—H261	120.5
C40—C41—H411	119.5	C27—C26—H261	120.0
C37^i—C41—H411	162.4	C26—C27—C22	121.2 (4)
C42—C41—H411	120.2	C26—C27—H271	118.9
H421^i—C42—C37	92.2	C22—C27—H271	119.9
H421^i—C42—C36^i	135.5	C24—O28—C29	117.2 (4)
C37—C42—C36^i	131.9 (8)	O28—C29—C30	106.3 (5)
H421^i—C42—C41	147.3	O28—C29—H291	110.4
C37—C42—C41	120.1 (4)	C30—C29—H291	108.0
C36^i—C42—C41	11.8 (7)	O28—C29—H292	111.4
H421^i—C42—C37^i	163.6	C30—C29—H292	109.6
C37—C42—C37^i	72.0 (10)	H291—C29—H292	111.0
C36^i—C42—C37^i	60.0 (11)	C29—C30—H301	111.7
C41—C42—C37^i	48.1 (10)	C29—C30—H302	110.6
H421^i—C42—C42^i	54.4	H301—C30—H302	107.6
C37—C42—C42^i	37.8 (4)	C29—C30—H303	110.8
C36^i—C42—C42^i	169.0 (7)	H301—C30—H303	108.3
C41—C42—C42^i	157.6 (5)	H302—C30—H303	107.6
C37^i—C42—C42^i	109.7 (10)	C25—O31—C32	116.0 (4)
H421^i—C42—H421	28.6	O31—C32—H322	108.9
C37—C42—H421	120.3	O31—C32—H323	110.2
C36^i—C42—H421	107.8	H322—C32—H323	109.3
C41—C42—H421	119.7	O31—C32—H321	110.4
C37^i—C42—H421	167.7	H322—C32—H321	108.6
C42^i—C42—H421	82.6	H323—C32—H321	109.3
C40^i—F33—C41^i	54.7 (6)	C40^i—H381—C38	84.4
C40^i—F33—H401^i	40.6	C40—H401—F33^i	81.6
C41^i—F33—H401^i	92.3	F35^i—H411—C41	107.5
C40^i—F33—C36	69.6 (9)	F35^i—H411—F34^i	135.7
C41^i—F33—C36	16.5 (8)	C41—H411—F34^i	91.0
H401^i—F33—C36	104.0	C42^i—H421—H421^i	54.5
C41^i—F34—H411^i	37.0	C42^i—H421—C42	43.0
C41^i—F34—C36	16.4 (7)	H421^i—H421—C42	97.0
H411^i—F34—C36	21.5

Symmetry code: (i) y, x, −z+1.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H52···O20^ii	0.98	2.41	3.383 (9)	168
C5—H51···O12	0.97	2.46	3.085 (9)	122
C5—H51···O12^i	0.97	2.32	3.134 (9)	141
C15—H151···O20	0.92	2.31	2.896 (9)	121
C23—H231···O12^i	0.93	2.47	3.401 (9)	178
C26—H261···O3^ii	0.94	2.42	3.344 (9)	169
C27—H271···O2^ii	0.95	2.53	3.263 (9)	134
C4—H41···O13^iii	0.98	2.41	3.070 (9)	125
N18—H181···O13	0.86	2.28	2.958 (9)	136

Symmetry codes: (i) y, x, −z+1; (ii) x+1/2, −y+1/2, −z+3/4; (iii) −y+1/2, x−1/2, z+1/4.