research papers\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

IUCrJ
Volume 9| Part 4| July 2022| Pages 508-515
ISSN: 2052-2525

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

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aDepartment of Chemical Engineering, University of Chemistry and Technology, Technická 3, Prague 6 16628, Czech Republic, bZentiva, k.s, U kabelovny 130, Prague 10 10237, Czech Republic, cDepartment of Solid State Chemistry, University of Chemistry and Technology, Technická 5, Prague 6 16628, Czech Republic, and dInstitute of Physics of the Czech Academy of Sciences, Na Slovance 2, Prague 8 18200, Czech Republic
*Correspondence e-mail: jirata@vscht.cz, soosm@vscht.cz

Edited by M. Eddaoudi, King Abdullah University, Saudi Arabia (Received 24 January 2022; accepted 22 May 2022; online 15 June 2022)

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[Good, D. J. & Rodríguez-Hornedo, N. (2009). Cryst. Growth Des. 9, 2252-2264.]; Blagden et al., 2007[Blagden, N., de Matas, M., Gavan, P. T. & York, P. (2007). Adv. Drug Deliv. Rev. 59, 617-630.]; Chen et al., 2011[Chen, H., Khemtong, C., Yang, X., Chang, X. & Gao, J. (2011). Drug Discovery Today, 16, 354-360.]). The biggest problem for oral drug administration – the most common method of treatment – is low bioavailability (Gavhane & Yadav, 2012[Gavhane, Y. N. & Yadav, A. V. (2012). Saudi Pharm. J. 20, 331-344.]; Pinnamaneni et al., 2002[Pinnamaneni, S., Das, N. G. & Das, S. K. (2002). Pharmazie, 57, 291-300.]), which is a consequence of poor aqueous solubility (Lipinski, 2000[Lipinski, C. A. (2000). J. Pharmacol. Toxicol. Methods, 44, 235-249.]). This issue is expected to be increasingly relevant in the coming years. In the current market, approximately 40% (Lipinski, 2002[Lipinski, C. (2002). Am. Pharm. Rev. 5, 82-85.]) of active pharmaceutical ingredients (APIs) have poor solubility and this number is expected to increase to 70–90% in the future (Thayer, 2010[Thayer, A. M. (2010). Chem. Eng. News Arch. 88, 13-18.]). 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[Qiao, N., Li, M., Schlindwein, W., Malek, N., Davies, A. & Trappitt, G. (2011). Int. J. Pharm. 419, 1-11.]; Jia et al., 2015[Jia, L., Zhang, Q., Wang, J.-R. & Mei, X. (2015). CrystEngComm, 17, 7500-7509.]; Stanton & Bak, 2008[Stanton, M. K. & Bak, A. (2008). Cryst. Growth Des. 8, 3856-3862.]). 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[de Moraes, L. S., Edwards, D., Florence, A. J., Johnston, A., Johnston, B. F., Morrison, C. A. & Kennedy, A. R. (2017). Cryst. Growth Des. 17, 3277-3286.]; Arlin et al., 2011[Arlin, J.-B., Florence, A. J., Johnston, A., Kennedy, A. R., Miller, G. J. & Patterson, K. (2011). Cryst. Growth Des. 11, 1318-1327.]; Collier et al., 2006[Collier, E. A., Davey, R. J., Black, S. N. & Roberts, R. J. (2006). Acta Cryst. B62, 498-505.]; Black et al., 2007[Black, S. N., Collier, E. A., Davey, R. J. & Roberts, R. J. (2007). J. Pharm. Sci. 96, 1053-1068.]). 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[Agharkar, S., Lindenbaum, S. & Higuchi, T. (1976). J. Pharm. Sci. 65, 747-749.]; Parshad et al., 2004[Parshad, H., Frydenvang, K., Liljefors, T., Sorensen, H. O. & Larsen, C. (2004). Int. J. Pharm. 269, 157-168.]). 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[Streng, W. H., Hsi, S. K., Helms, P. E. & Tan, H. G. H. (1984). J. Pharm. Sci. 73, 1679-1684.]). 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[Sanphui, P., Bolla, G., Nangia, A. & Chernyshev, V. (2014). IUCrJ, 1, 136-150.]; Mannava et al., 2020[Mannava, M. K. C., Dandela, R., Tothadi, S., Solomon, K. A. & Nangia, A. K. (2020). Cryst. Growth Des. 20, 3064-3076.]; Gunnam & Nangia, 2019[Gunnam, A. & Nangia, A. K. (2019). Cryst. Growth Des. 19, 5407-5417.]; Banik et al., 2016[Banik, M., Gopi, S. P., Ganguly, S. & Desiraju, G. R. (2016). Cryst. Growth Des. 16, 5418-5428.]; Martin et al., 2013[Martin, F. A., Pop, M. M., Borodi, G., Filip, X. & Kacso, I. (2013). Cryst. Growth Des. 13, 4295-4304.]; Thakuria & Nangia, 2013[Thakuria, R. & Nangia, A. (2013). Cryst. Growth Des. 13, 3672-3680.]; Goud et al., 2013[Goud, N. R., Suresh, K. & Nangia, A. (2013). Cryst. Growth Des. 13, 1590-1601.]). Several studies with systematic large datasets are now available (20–50 salts) that bring new insight into this topic (de Moraes et al., 2017[de Moraes, L. S., Edwards, D., Florence, A. J., Johnston, A., Johnston, B. F., Morrison, C. A. & Kennedy, A. R. (2017). Cryst. Growth Des. 17, 3277-3286.]; Arlin et al., 2011[Arlin, J.-B., Florence, A. J., Johnston, A., Kennedy, A. R., Miller, G. J. & Patterson, K. (2011). Cryst. Growth Des. 11, 1318-1327.]; Collier et al., 2006[Collier, E. A., Davey, R. J., Black, S. N. & Roberts, R. J. (2006). Acta Cryst. B62, 498-505.]; Black et al., 2007[Black, S. N., Collier, E. A., Davey, R. J. & Roberts, R. J. (2007). J. Pharm. Sci. 96, 1053-1068.]). 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[Cadden, J., Klooster, W. T., Coles, S. J. & Aitipamula, S. (2019). Cryst. Growth Des. 19, 3923-3933.]). 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[Stanton, M. K. & Bak, A. (2008). Cryst. Growth Des. 8, 3856-3862.]). 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[Stepanovs, D., Jure, M., Kuleshova, L. N., Hofmann, D. W. M. & Mishnev, A. (2015). Cryst. Growth Des. 15, 3652-3660.]; Stanton & Bak, 2008[Stanton, M. K. & Bak, A. (2008). Cryst. Growth Des. 8, 3856-3862.]; Aakeröy et al., 2006[Aakeröy, C. B., Hussain, I. & Desper, J. (2006). Cryst. Growth Des. 6, 474-480.]). A different, more detailed analysis of cocrystal melting points across a broader system of compounds was performed by Schultheiss & Newman (2009[Schultheiss, N. & Newman, A. (2009). Cryst. Growth Des. 9, 2950-2967.]), 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[Zvoníček, V., Skořepová, E., Dušek, M., Žvátora, P. & Šoóš, M. (2018). Cryst. Growth Des. 18, 1315-1326.]; Aguiar et al., 1967[Aguiar, A. J., Krc, J. Jr, Kinkel, A. W. & Samyn, J. C. (1967). J. Pharm. Sci. 56, 847-853.]; Aguiar & Zelmer, 1969[Aguiar, A. J. & Zelmer, J. E. (1969). J. Pharm. Sci. 58, 983-987.]; Bauer et al., 2001[Bauer, J., Spanton, S., Henry, R., Quick, J., Dziki, W., Porter, W. & Morris, J. (2001). Pharm. Res. 18, 859-866.]). 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[de Moraes, L. S., Edwards, D., Florence, A. J., Johnston, A., Johnston, B. F., Morrison, C. A. & Kennedy, A. R. (2017). Cryst. Growth Des. 17, 3277-3286.]).

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[Degen, T., Sadki, M., Bron, E., König, U. & Nénert, G. (2014). Powder Diffr. 29, S13-S18.]) 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[Rigaku Oxford Diffraction (2019). CrysAlisPro. Rigaku Oxford Diffraction, Yarnton, UK.]). The structure was solved by charge flipping methods using the Superflip software (Palatinus & Chapuis, 2007[Palatinus, L. & Chapuis, G. (2007). J. Appl. Cryst. 40, 786-790.]) and refined by full matrix least squares on the F-squared value using the Crystals software (Betteridge et al., 2003[Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487-1487.]). The MCE software (Rohlíček & Hušák, 2007[Rohlíček, J. & Hušák, M. (2007). J. Appl. Cryst. 40, 600-601.]) was used for visualization of residual electron density maps. According to common practice, hydrogen atoms attached to carbon atoms were assigned geometrically with Uiso (H) in the range 1.2–1.5 Ueq 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[Zerilli, T. & Ocheretyaner, E. (2015). Pharmacol. Ther. 40, 495-500.]; Afra et al., 2019[Afra, T. P., Razmi, T. M. & Dogra, S. (2019). Dermatol. Online J. 10, 1-12.]). 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[Wu, Y. D., Zhang, X. L., Liu, X. H., Xu, J., Zhang, M., Shen, K., Zhang, S. H., He, Y. M., Ma, Y. & Zhang, A. H. (2017). Acta Cryst. C73, 305-313.]; Jirát et al., 2019[Jirát, J., Ondo, D., Babor, M., Ridvan, L. & Šoóš, M. (2019). Int. J. Pharm. 570, 118639.], 2020[Jirát, J., Zvoníček, V., Babor, M., Ridvan, L., Skořepová, E., Dušek, M. & Šoóš, M. (2020). Cryst. Growth Des. 20, 5785-5795.]) 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 (24HBC), 2,5-di­hydroxy­benzoic acid (25HBC), 4-hy­droxy­benzoic acid (4HBC), nicotinamide (NCAC) and salicylic acid (SCAC); and solvates with anisole (ANIS), bromo­benzene (BRBS), chloro­benzene (CLBS), hexa­fluoro­benzene (HFBs), iodo­benzene (IOBS), mesitylene (MSTS), m-xylene (MXYS), p-xylene (PXYS) and α,α,α-tri­fluoro­toluene (TFTS). Other multicomponent forms from the literature (Wu et al., 2017[Wu, Y. D., Zhang, X. L., Liu, X. H., Xu, J., Zhang, M., Shen, K., Zhang, S. H., He, Y. M., Ma, Y. & Zhang, A. H. (2017). Acta Cryst. C73, 305-313.]; Jirát et al., 2019[Jirát, J., Ondo, D., Babor, M., Ridvan, L. & Šoóš, M. (2019). Int. J. Pharm. 570, 118639.], 2020[Jirát, J., Zvoníček, V., Babor, M., Ridvan, L., Skořepová, E., Dušek, M. & Šoóš, M. (2020). Cryst. Growth Des. 20, 5785-5795.]) and used in this study crystallized with phthalic acid (PHTC), benzoic acid (BACC), toluene (TOLS), o-xylene (OXYS) and fluoro­benzene (FLBS). Their respective chemical structures together with that of apremilast are presented in Fig. 1[link].

[Figure 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[Jirát, J., Zvoníček, V., Babor, M., Ridvan, L., Skořepová, E., Dušek, M. & Šoóš, M. (2020). Cryst. Growth Des. 20, 5785-5795.]; Dudek et al., 2019[Dudek, M. K., Wielgus, E., Paluch, P., Śniechowska, J., Kostrzewa, M., Day, G. M., Bujacz, G. D. & Potrzebowski, M. J. (2019). Acta Cryst. B75, 803-814.]), 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 ππ 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[link]).

[Figure 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[link](a) using the CrystalCMP software (Rohlíček et al., 2016[Rohlíček, J., Skořepová, E., Babor, M. & Čejka, J. (2016). J. Appl. Cryst. 49, 2172-2183.]) 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[link](b) and 2(d) and one in between [Fig. 2[link](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, Tm), 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[link]).

[Figure 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 R2 of 0.1366.

Data presented in Fig. 3[link] 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[Schultheiss, N. & Newman, A. (2009). Cryst. Growth Des. 9, 2950-2967.]; Stepanovs et al., 2015[Stepanovs, D., Jure, M., Kuleshova, L. N., Hofmann, D. W. M. & Mishnev, A. (2015). Cryst. Growth Des. 15, 3652-3660.]; Stanton & Bak, 2008[Stanton, M. K. & Bak, A. (2008). Cryst. Growth Des. 8, 3856-3862.]; Aakeröy et al., 2006[Aakeröy, C. B., Hussain, I. & Desper, J. (2006). Cryst. Growth Des. 6, 474-480.]). However, there are studies that report similar results to ours (Stanton et al., 2009[Stanton, M. K., Tufekcic, S., Morgan, C. & Bak, A. (2009). Cryst. Growth Des. 9, 1344-1352.]). 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[link], 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[link] 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[Stanton, M. K. & Bak, A. (2008). Cryst. Growth Des. 8, 3856-3862.]) or no correlation at all (Stanton et al., 2009[Stanton, M. K., Tufekcic, S., Morgan, C. & Bak, A. (2009). Cryst. Growth Des. 9, 1344-1352.]), 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]
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 R2 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[link](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]
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 R2 of 0.56 with outliers and an R2 of 0.94 without outliers marked with black circles. A linear fit of the data in (b) gives an R2 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[Dudek, M. K., Kostrzewa, M., Paluch, P. & Potrzebowski, M. J. (2018). Cryst. Growth Des. 18, 3959-3970.]); Wang et al. (2018[Wang, F. Y., Zhang, Q., Zhang, Z. Y., Gong, X. Y., Wang, J. R. & Mei, X. F. S. (2018). CrystEngComm, 20, 5945-5948.]); Chiou et al. (1977[Chiou, C. T., Freed, V. H., Schmedding, D. W. & Kohnert, R. L. (1977). Environ. Sci. Technol. 11, 475-478.]); Valvanix et al. (1981[Valvanix, S. C., Yalkowsky, S. H. & Roseman, T. J. (1981). J. Pharm. Sci. 70, 502-507.]); Isao et al. (1982[Isao, S., Masatake, A., Toshio, D. & Hideo, N. (1982). Bull. Chem. Soc. Jpn. 55, 1054-1062.]); Freire et al. (2005[Freire, M. G., Razzouk, A., Mokbel, I., Jose, J., Marrucho, I. M. & Coutinho, J. A. P. S. (2005). J. Chem. Eng. Data, 50, 237-242.]); Van Arnum (2000[Van Arnum, S. D. (2000). Kirk-Othmer Encyclopedia of Chemical Technology. New York: John Wiley.]); Nian (2016[Nian, J. (2016). Patent WO 2016141503 A1.]); Yalkowsky & Dannenfleser (1992[Yalkowsky, R. M. & Dannenfleser, S. H. (1992). Aquasol Database of Aqueous Solubility, version 5. Tucson, AZ: University of Arizona.]); Yalkowsky & He (1992[Yalkowsky, S. H. & He, Y. (2003). Handbook of Aqueous Solubility Data. Boca Raton, FL: CRC Press.]); Yalkowsky et al. (2010[Yalkowsky, S. H., He, Y. & Jain, P. (2010). Handbook of Aqueous Solubility Data, 2nd ed. Boca Raton, FL: CRC Press.]).

Supporting information


Computing details top

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) top
Crystal data top
C25.50H26N2O9SDx = 1.452 Mg m3
Mr = 536.56Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 56131 reflections
a = 12.9189 (1) Åθ = 4–68°
c = 29.4056 (1) ŵ = 1.69 mm1
V = 4907.74 (8) Å3T = 120 K
Z = 8Prism, colorles
F(000) = 22480.37 × 0.17 × 0.15 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4409 reflections with I > 2.0σ(I)
Focussing mirrors monochromatorRint = 0.033
ω scansθmax = 67.9°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro (Rigaku Oxford Diffraction, 2017)
h = 1515
Tmin = 0.66, Tmax = 0.77k = 1515
94480 measured reflectionsl = 3535
4464 independent reflections
Refinement top
Refinement on F2H-atom parameters constrained
Least-squares matrix: full Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.07P)2 + 5.73P] ,
where P = (max(Fo2,0) + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.048(Δ/σ)max = 0.006
wR(F2) = 0.130Δρmax = 0.64 e Å3
S = 1.00Δρmin = 0.61 e Å3
4462 reflectionsExtinction correction: Larson (1970), Equation 22
363 parametersExtinction coefficient: 107 (19)
62 restraintsAbsolute structure: Parsons, Flack & Wagner (2013), 1809 Friedel Pairs
Primary atom site location: otherAbsolute structure parameter: 0.013 (3)
Hydrogen site location: difference Fourier map
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.40546 (6)0.16440 (6)0.46468 (3)0.0289
O20.31274 (19)0.21203 (19)0.44718 (8)0.0370
O30.4471 (2)0.07730 (18)0.44010 (8)0.0386
C40.3821 (3)0.1275 (3)0.52101 (13)0.0441
C50.5021 (2)0.2600 (2)0.47030 (10)0.0269
C60.5468 (2)0.2970 (2)0.42509 (9)0.0251
N70.4660 (2)0.34496 (19)0.39634 (8)0.0250
C80.4006 (3)0.4253 (2)0.40933 (10)0.0274
C90.3257 (3)0.4402 (2)0.37216 (10)0.0274
C100.3478 (2)0.3684 (2)0.33859 (10)0.0256
C110.4382 (2)0.3066 (2)0.35353 (10)0.0247
O120.40790 (19)0.47246 (17)0.44530 (7)0.0318
O130.48132 (18)0.23543 (17)0.33397 (7)0.0294
C140.2444 (3)0.5096 (3)0.36805 (12)0.0338
C150.1879 (3)0.5043 (3)0.32802 (13)0.0369
C160.2100 (3)0.4341 (3)0.29397 (12)0.0322
C170.2922 (2)0.3638 (2)0.29797 (10)0.0263
N180.3217 (2)0.2917 (2)0.26546 (9)0.0285
C190.2803 (3)0.2741 (2)0.22319 (10)0.0293
C200.3406 (3)0.2003 (3)0.19450 (11)0.0368
O210.20114 (18)0.31641 (19)0.20976 (8)0.0362
C220.6391 (2)0.3685 (2)0.43213 (11)0.0280
C230.6540 (3)0.4246 (2)0.47225 (11)0.0289
C240.7397 (3)0.4877 (3)0.47793 (11)0.0317
C250.8129 (3)0.4958 (3)0.44257 (13)0.0344
C260.7984 (3)0.4404 (3)0.40301 (12)0.0356
C270.7112 (3)0.3767 (3)0.39780 (11)0.0333
O280.75982 (18)0.5458 (2)0.51598 (9)0.0403
C290.6819 (3)0.5451 (3)0.55083 (13)0.0422
C300.7110 (3)0.6244 (4)0.58608 (18)0.0690
O310.89655 (19)0.5588 (2)0.45102 (10)0.0448
C320.9668 (3)0.5729 (4)0.41403 (15)0.0639
O330.4478 (12)0.7014 (12)0.3284 (6)0.17360.5000
O340.3565 (11)0.7443 (11)0.2666 (5)0.17210.5000
C350.3952 (11)0.6748 (7)0.2952 (6)0.15560.5000
C360.4462 (5)0.5840 (5)0.27224 (7)0.1166
C370.5276 (5)0.5306 (6)0.2923 (3)0.1334
C380.5796 (5)0.4505 (6)0.2708 (2)0.1165
O390.6562 (9)0.4193 (10)0.2966 (5)0.17180.5000
O400.5628 (9)0.5519 (10)0.3320 (4)0.16980.5000
H520.55740.22910.48830.0328*
H510.47200.31940.48600.0326*
H610.57060.23580.40900.0292*
H2020.29930.17750.16870.0549*
H2010.40360.23050.18300.0559*
H2030.36000.13890.21130.0555*
H1610.16830.43380.26740.0380*
H1510.12970.55040.32460.0448*
H1410.23040.55750.39160.0402*
H2710.70200.33610.37020.0391*
H2610.84700.44190.37940.0407*
H3211.02150.62070.42330.0897*
H3230.99900.50660.40670.0905*
H3220.93090.59930.38790.0899*
H2310.60550.41910.49630.0321*
H2920.67890.47540.56440.0512*
H2910.61300.56040.53840.0513*
H3010.65490.63420.60740.0952*
H3030.77470.60400.60160.0946*
H3020.72160.68770.56950.0949*
H410.44550.09710.53300.0648*
H430.36270.18840.53890.0646*
H420.32590.07810.52060.0651*
H1810.37240.25380.27310.0317*
H3710.54630.55240.32220.1504*0.5000
H3810.63440.41590.28640.1383*0.5000
H3610.40790.63560.28900.1400*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0316 (4)0.0278 (4)0.0273 (3)0.0053 (3)0.0007 (3)0.0030 (3)
O20.0323 (12)0.0407 (13)0.0381 (12)0.0017 (10)0.0072 (10)0.0004 (11)
O30.0432 (13)0.0300 (12)0.0427 (13)0.0035 (10)0.0018 (11)0.0033 (10)
C40.050 (2)0.044 (2)0.0381 (18)0.0080 (17)0.0045 (16)0.0155 (16)
C50.0318 (16)0.0272 (15)0.0217 (13)0.0040 (12)0.0006 (12)0.0015 (12)
C60.0280 (15)0.0254 (14)0.0220 (13)0.0006 (12)0.0016 (12)0.0015 (11)
N70.0305 (13)0.0238 (12)0.0208 (11)0.0001 (10)0.0049 (10)0.0025 (10)
C80.0321 (16)0.0227 (15)0.0275 (15)0.0006 (13)0.0077 (13)0.0008 (12)
C90.0310 (16)0.0234 (14)0.0276 (14)0.0034 (12)0.0051 (13)0.0031 (12)
C100.0277 (15)0.0219 (14)0.0272 (14)0.0033 (12)0.0065 (12)0.0012 (11)
C110.0310 (16)0.0224 (14)0.0207 (13)0.0042 (12)0.0054 (12)0.0016 (11)
O120.0421 (13)0.0281 (11)0.0252 (10)0.0002 (10)0.0043 (10)0.0063 (9)
O130.0335 (12)0.0287 (11)0.0259 (10)0.0048 (9)0.0025 (9)0.0042 (9)
C140.0365 (17)0.0279 (16)0.0369 (17)0.0025 (14)0.0045 (14)0.0078 (14)
C150.0338 (18)0.0304 (17)0.0467 (19)0.0077 (14)0.0016 (15)0.0059 (15)
C160.0292 (16)0.0295 (16)0.0379 (18)0.0009 (13)0.0004 (14)0.0042 (13)
C170.0276 (15)0.0252 (15)0.0260 (15)0.0022 (12)0.0027 (12)0.0006 (12)
N180.0261 (13)0.0298 (14)0.0294 (13)0.0044 (11)0.0008 (11)0.0043 (11)
C190.0310 (17)0.0301 (16)0.0268 (15)0.0040 (13)0.0025 (13)0.0004 (13)
C200.0393 (18)0.0420 (19)0.0289 (16)0.0009 (16)0.0021 (14)0.0069 (14)
O210.0346 (12)0.0401 (13)0.0339 (12)0.0043 (11)0.0050 (10)0.0006 (10)
C220.0298 (16)0.0244 (15)0.0298 (15)0.0013 (13)0.0035 (12)0.0012 (12)
C230.0312 (16)0.0251 (15)0.0305 (15)0.0013 (12)0.0087 (13)0.0029 (12)
C240.0271 (16)0.0278 (16)0.0401 (17)0.0007 (12)0.0029 (13)0.0030 (13)
C250.0277 (16)0.0264 (16)0.0493 (19)0.0012 (13)0.0037 (14)0.0090 (15)
C260.0338 (17)0.0355 (18)0.0376 (17)0.0038 (14)0.0107 (15)0.0105 (14)
C270.0335 (17)0.0357 (18)0.0308 (16)0.0045 (13)0.0078 (14)0.0039 (14)
O280.0306 (12)0.0377 (13)0.0525 (14)0.0045 (10)0.0049 (11)0.0154 (11)
C290.0288 (17)0.051 (2)0.0470 (19)0.0015 (15)0.0022 (15)0.0220 (18)
C300.038 (2)0.093 (4)0.075 (3)0.002 (2)0.000 (2)0.053 (3)
O310.0297 (12)0.0453 (14)0.0596 (16)0.0089 (11)0.0061 (12)0.0110 (13)
C320.032 (2)0.105 (4)0.054 (2)0.024 (2)0.0044 (18)0.041 (3)
O330.145 (9)0.175 (10)0.201 (11)0.010 (9)0.007 (9)0.058 (9)
O340.157 (9)0.179 (10)0.180 (10)0.062 (8)0.031 (8)0.056 (8)
C350.137 (8)0.151 (8)0.179 (9)0.017 (7)0.008 (7)0.052 (7)
C360.097 (5)0.111 (5)0.142 (6)0.042 (4)0.024 (4)0.043 (4)
C370.108 (5)0.155 (6)0.137 (6)0.076 (4)0.015 (4)0.037 (5)
C380.072 (4)0.140 (6)0.137 (6)0.024 (4)0.028 (4)0.050 (5)
O390.106 (7)0.198 (10)0.212 (10)0.003 (8)0.016 (8)0.044 (9)
O400.157 (8)0.187 (9)0.166 (9)0.079 (8)0.005 (8)0.032 (9)
Geometric parameters (Å, º) top
S1—O21.442 (3)C22—C231.397 (4)
S1—O31.441 (3)C22—C271.378 (4)
S1—C41.750 (4)C23—C241.385 (4)
S1—C51.764 (3)C23—H2310.948
C4—H410.975C24—C251.409 (5)
C4—H430.978C24—O281.372 (4)
C4—H420.966C25—C261.378 (5)
C5—C61.526 (4)C25—O311.375 (4)
C5—H520.975C26—C271.405 (5)
C5—H510.977C26—H2610.936
C6—N71.479 (4)C27—H2710.973
C6—C221.522 (4)O28—C291.437 (4)
C6—H610.972C29—C301.506 (5)
N7—C81.393 (4)C29—H2920.985
N7—C111.400 (4)C29—H2910.983
C8—C91.472 (5)C30—H3010.967
C8—O121.224 (4)C30—H3030.977
C9—C101.385 (4)C30—H3020.962
C9—C141.386 (5)O31—C321.428 (5)
C10—C111.480 (4)C32—H3210.977
C10—C171.395 (4)C32—H3230.976
C11—O131.220 (4)C32—H3220.960
C14—C151.387 (5)O33—C351.240 (15)
C14—H1410.945O34—C351.327 (19)
C15—C161.380 (5)C35—C361.505 (9)
C15—H1510.964C36—C36i1.4193 (11)
C16—C171.403 (5)C36—C371.389 (5)
C16—H1610.949C36—C371.389 (5)
C17—N181.388 (4)C36—H3610.966
N18—C191.372 (4)C37—C381.386 (11)
N18—H1810.848C37—H3710.956
C19—C201.493 (5)C37—C381.386 (11)
C19—O211.225 (4)C37—O401.284 (9)
C20—H2020.973C38—C38i1.342 (16)
C20—H2010.964C38—O391.311 (13)
C20—H2030.966C38—H3810.954
O2—S1—O3117.66 (15)H202—C20—H201108.2
O2—S1—C4108.11 (18)C19—C20—H203111.8
O3—S1—C4109.04 (18)H202—C20—H203106.9
O2—S1—C5108.82 (15)H201—C20—H203107.0
O3—S1—C5109.25 (15)C6—C22—C23122.5 (3)
C4—S1—C5102.95 (17)C6—C22—C27118.4 (3)
S1—C4—H41107.9C23—C22—C27119.1 (3)
S1—C4—H43109.5C22—C23—C24121.2 (3)
H41—C4—H43110.2C22—C23—H231120.0
S1—C4—H42107.2C24—C23—H231118.8
H41—C4—H42111.7C23—C24—C25119.4 (3)
H43—C4—H42110.2C23—C24—O28124.9 (3)
S1—C5—C6113.9 (2)C25—C24—O28115.7 (3)
S1—C5—H52106.5C24—C25—C26119.5 (3)
C6—C5—H52108.9C24—C25—O31116.0 (3)
S1—C5—H51108.2C26—C25—O31124.5 (3)
C6—C5—H51108.5C25—C26—C27120.4 (3)
H52—C5—H51110.9C25—C26—H261121.6
C5—C6—N7111.2 (2)C27—C26—H261118.0
C5—C6—C22111.6 (2)C26—C27—C22120.5 (3)
N7—C6—C22112.1 (2)C26—C27—H271120.3
C5—C6—H61106.8C22—C27—H271119.2
N7—C6—H61106.6C24—O28—C29116.5 (3)
C22—C6—H61108.2O28—C29—C30108.2 (3)
C6—N7—C8125.7 (2)O28—C29—H292108.8
C6—N7—C11123.2 (2)C30—C29—H292110.6
C8—N7—C11110.8 (3)O28—C29—H291111.5
N7—C8—C9107.0 (2)C30—C29—H291110.3
N7—C8—O12124.1 (3)H292—C29—H291107.4
C9—C8—O12128.9 (3)C29—C30—H301110.3
C8—C9—C10107.8 (3)C29—C30—H303110.4
C8—C9—C14130.3 (3)H301—C30—H303111.5
C10—C9—C14121.8 (3)C29—C30—H302105.4
C9—C10—C11108.2 (3)H301—C30—H302108.9
C9—C10—C17122.2 (3)H303—C30—H302110.3
C11—C10—C17129.6 (3)C25—O31—C32115.9 (3)
C10—C11—N7106.2 (2)O31—C32—H321109.1
C10—C11—O13128.8 (3)O31—C32—H323109.0
N7—C11—O13125.0 (3)H321—C32—H323107.9
C9—C14—C15116.1 (3)O31—C32—H322110.4
C9—C14—H141120.3H321—C32—H322110.4
C15—C14—H141123.6H323—C32—H322109.9
C14—C15—C16122.7 (3)O34—C35—O33121.2 (5)
C14—C15—H151117.9O34—C35—C36114.1 (12)
C16—C15—H151119.4O33—C35—C36109.2 (14)
C15—C16—C17121.4 (3)C35—C36—C36i120.4 (8)
C15—C16—H161118.9C35—C36—C37121.9 (8)
C17—C16—H161119.7C36i—C36—C37117.6 (4)
C16—C17—C10115.7 (3)C37—C36—H361120.9
C16—C17—N18125.8 (3)C36—C37—C38123.0 (7)
C10—C17—N18118.5 (3)C36—C37—H371115.9
C17—N18—C19128.9 (3)C38—C37—H371121.2
C17—N18—H181114.7C36—C37—C38123.0 (7)
C19—N18—H181116.5C36—C37—O40123.2 (8)
N18—C19—C20114.5 (3)C38—C37—O40113.8 (9)
N18—C19—O21123.0 (3)C37—C38—C38i119.5 (4)
C20—C19—O21122.6 (3)C37—C38—O39109.4 (8)
C19—C20—H202110.4C38i—C38—O39131.1 (7)
C19—C20—H201112.3C37—C38—H381119.4
Symmetry code: (i) y+1, x+1, z+1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H52···O21ii0.982.473.437 (6)169
C5—H51···O120.982.463.091 (6)122
C5—H51···O12iii0.982.323.155 (6)143
C16—H161···O210.952.312.908 (6)120
C27—H271···O2ii0.972.523.292 (6)136
C27—H271···O390.972.493.108 (6)121
C26—H261···O3ii0.942.433.352 (6)168
C32—H321···O21iv0.982.573.521 (6)164
C23—H231···O12iii0.952.433.380 (6)176
C30—H301···O40iii0.972.413.264 (6)148
C4—H43···O2iii0.982.563.381 (6)142
C4—H42···O13v0.972.383.049 (6)126
N18—H181···O130.852.292.973 (6)138
C36—H361···O330.971.532.242 (6)127
C36—H361···O340.971.692.379 (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, x1/2, z+1/4.
(apremilast25dihydrbenzoic) top
Crystal data top
2(C22H24N2O7S)·C7H5O4Dx = 1.455 Mg m3
Mr = 1074.13Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 44445 reflections
a = 12.9170 (1) Åθ = 4–68°
c = 29.3859 (2) ŵ = 1.69 mm1
V = 4903.00 (8) Å3T = 120 K
Z = 4Block, colorless
F(000) = 22520.44 × 0.25 × 0.18 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4287 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.052
ω scansθmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.50, Tmax = 0.74k = 1515
88004 measured reflectionsl = 3535
4443 independent reflections
Refinement top
Refinement on F2H-atom parameters constrained
Least-squares matrix: full Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.04P)2 + 5.29P] ,
where P = (max(Fo2,0) + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.039(Δ/σ)max = 0.001
wR(F2) = 0.102Δρmax = 0.62 e Å3
S = 1.00Δρmin = 0.35 e Å3
4443 reflectionsExtinction correction: Larson (1970), Equation 22
354 parametersExtinction coefficient: 40 (10)
12 restraintsAbsolute structure: Flack (1983), 1825 Friedel-pairs
Primary atom site location: OtherAbsolute structure parameter: 0.01 (2)
Hydrogen site location: difference Fourier map
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
C250.5042 (2)0.1875 (2)0.55976 (11)0.0355
C260.5615 (2)0.2033 (2)0.59904 (9)0.0330
C270.6255 (2)0.2892 (2)0.60293 (9)0.0303
O310.43988 (16)0.10517 (16)0.55214 (8)0.0446
C320.4307 (3)0.0329 (2)0.58867 (11)0.0476
O330.4586 (2)0.4452 (2)0.66175 (11)0.0755
C340.4822 (3)0.4701 (3)0.70577 (15)0.0632
C350.5621 (3)0.4127 (3)0.72862 (14)0.0677
C360.4271 (3)0.5448 (3)0.72585 (16)0.0699
C370.3315 (6)0.5860 (5)0.7117 (2)0.04630.5000
O380.2667 (4)0.6382 (4)0.7402 (2)0.07150.5000
O390.2990 (4)0.5734 (5)0.67285 (18)0.06710.5000
S10.83604 (5)0.59448 (5)0.53437 (2)0.0299
O20.78956 (16)0.68728 (15)0.55285 (7)0.0375
O30.92423 (15)0.55178 (16)0.55801 (7)0.0393
C40.8696 (3)0.6198 (3)0.47754 (10)0.0453
C50.7395 (2)0.4977 (2)0.52909 (8)0.0278
C60.7036 (2)0.4534 (2)0.57468 (8)0.0277
N70.65685 (16)0.53448 (17)0.60330 (7)0.0264
C80.69483 (19)0.5627 (2)0.64622 (8)0.0267
C90.63248 (19)0.6518 (2)0.66146 (8)0.0275
C100.5601 (2)0.6743 (2)0.62778 (9)0.0297
C110.5748 (2)0.5990 (2)0.59047 (9)0.0293
O120.76625 (14)0.51926 (14)0.66547 (6)0.0307
O130.52704 (14)0.59080 (15)0.55500 (6)0.0345
C140.6370 (2)0.7079 (2)0.70173 (9)0.0299
C150.5670 (2)0.7897 (2)0.70637 (10)0.0367
C160.4959 (2)0.8121 (2)0.67201 (11)0.0415
C170.4901 (2)0.7541 (2)0.63219 (10)0.0365
N180.70915 (17)0.67778 (17)0.73461 (7)0.0303
C190.7258 (2)0.7197 (2)0.77668 (9)0.0319
C200.8005 (2)0.6589 (2)0.80570 (9)0.0395
O210.68334 (16)0.79817 (15)0.79018 (6)0.0380
C220.6326 (2)0.3613 (2)0.56825 (9)0.0283
C230.5745 (2)0.3460 (2)0.52862 (9)0.0329
C240.5104 (2)0.2603 (2)0.52422 (10)0.0369
H2610.55710.15460.62310.0383*
H2710.66550.30050.62980.0376*
H3230.38250.01900.57700.0704*
H3220.40140.06940.61490.0717*
H3210.49800.00150.59550.0714*
H3510.59390.35640.71400.0795*
H410.89500.55660.46420.0684*
H420.92340.67020.47860.0685*
H430.80910.64400.46080.0692*
H520.77380.44400.51110.0332*
H510.68140.52940.51240.0334*
H610.76730.43190.59070.0335*
H1510.56800.83080.73280.0439*
H1610.44950.86990.67630.0503*
H1710.44070.76840.60990.0449*
H2010.82390.70080.83040.0588*
H2020.86170.63690.78820.0582*
H2030.76520.59860.81770.0586*
H2310.57940.39660.50490.0382*
H1810.74840.62720.72660.0361*
H3810.21650.65990.72390.1199*0.5000
H3310.39740.46470.65210.1127*
C300.3675 (4)0.2840 (3)0.41731 (15)0.0758
C290.4506 (3)0.3149 (2)0.45068 (11)0.0496
O280.44996 (19)0.23946 (16)0.48695 (8)0.0536
H2910.43740.38210.46250.0601*
H2920.51580.31440.43580.0601*
H3010.30910.25800.43330.0943*
H3020.34750.34250.39980.0943*
H3030.39370.23170.39770.0943*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C250.0269 (13)0.0285 (14)0.0511 (17)0.0038 (11)0.0029 (12)0.0100 (12)
C260.0307 (14)0.0343 (14)0.0341 (14)0.0031 (11)0.0044 (11)0.0082 (12)
C270.0301 (14)0.0309 (14)0.0301 (13)0.0035 (10)0.0014 (11)0.0033 (11)
O310.0421 (12)0.0303 (10)0.0613 (13)0.0117 (9)0.0067 (10)0.0148 (10)
C320.069 (2)0.0289 (15)0.0454 (17)0.0122 (15)0.0194 (16)0.0002 (13)
O330.0679 (18)0.0644 (17)0.094 (2)0.0030 (14)0.0027 (17)0.0007 (16)
C340.062 (2)0.051 (2)0.076 (3)0.0094 (18)0.011 (2)0.0029 (19)
C350.0409 (19)0.063 (2)0.100 (3)0.0041 (18)0.020 (2)0.024 (2)
C360.057 (2)0.057 (2)0.096 (3)0.0130 (19)0.006 (2)0.002 (2)
C370.061 (4)0.035 (3)0.043 (3)0.012 (3)0.007 (3)0.013 (3)
O380.072 (4)0.065 (3)0.078 (4)0.024 (3)0.012 (3)0.020 (3)
O390.057 (3)0.083 (4)0.062 (3)0.016 (3)0.004 (3)0.018 (3)
S10.0296 (3)0.0307 (3)0.0293 (3)0.0057 (3)0.0029 (3)0.0027 (3)
O20.0447 (11)0.0311 (10)0.0365 (10)0.0021 (9)0.0018 (9)0.0067 (8)
O30.0310 (10)0.0413 (11)0.0457 (12)0.0038 (8)0.0044 (9)0.0023 (9)
C40.0523 (19)0.0456 (18)0.0380 (16)0.0105 (14)0.0155 (14)0.0005 (13)
C50.0286 (13)0.0298 (13)0.0249 (12)0.0059 (10)0.0007 (10)0.0018 (11)
C60.0270 (13)0.0320 (13)0.0242 (12)0.0000 (11)0.0017 (10)0.0003 (10)
N70.0237 (10)0.0342 (12)0.0212 (10)0.0005 (9)0.0029 (8)0.0012 (9)
C80.0255 (12)0.0311 (13)0.0236 (11)0.0050 (10)0.0017 (10)0.0030 (10)
C90.0251 (12)0.0304 (13)0.0271 (12)0.0019 (10)0.0013 (10)0.0043 (10)
C100.0267 (13)0.0322 (14)0.0301 (12)0.0001 (11)0.0041 (10)0.0053 (11)
C110.0273 (13)0.0335 (14)0.0271 (12)0.0021 (11)0.0010 (11)0.0056 (11)
O120.0320 (10)0.0323 (10)0.0277 (9)0.0041 (8)0.0062 (8)0.0013 (8)
O130.0309 (10)0.0447 (11)0.0281 (9)0.0007 (9)0.0069 (8)0.0032 (8)
C140.0293 (13)0.0290 (14)0.0315 (14)0.0009 (11)0.0029 (11)0.0028 (11)
C150.0333 (15)0.0378 (15)0.0391 (15)0.0076 (12)0.0065 (12)0.0052 (12)
C160.0386 (16)0.0383 (16)0.0477 (17)0.0131 (13)0.0109 (13)0.0052 (13)
C170.0322 (14)0.0373 (15)0.0399 (15)0.0064 (12)0.0077 (12)0.0033 (12)
N180.0322 (12)0.0293 (11)0.0294 (11)0.0049 (9)0.0061 (9)0.0023 (9)
C190.0324 (14)0.0342 (15)0.0292 (13)0.0031 (12)0.0014 (11)0.0013 (11)
C200.0489 (17)0.0384 (16)0.0312 (14)0.0025 (14)0.0111 (13)0.0003 (12)
O210.0452 (11)0.0365 (11)0.0323 (10)0.0069 (9)0.0019 (9)0.0045 (8)
C220.0266 (13)0.0320 (14)0.0262 (12)0.0006 (11)0.0008 (10)0.0038 (10)
C230.0324 (14)0.0319 (13)0.0344 (13)0.0063 (11)0.0071 (11)0.0112 (12)
C240.0331 (15)0.0340 (14)0.0434 (15)0.0062 (11)0.0134 (12)0.0091 (12)
C300.104 (3)0.0416 (19)0.082 (3)0.021 (2)0.063 (2)0.0170 (18)
C290.069 (2)0.0283 (14)0.0517 (18)0.0106 (14)0.0340 (17)0.0109 (13)
O280.0616 (14)0.0350 (11)0.0642 (15)0.0205 (10)0.0373 (12)0.0205 (10)
Geometric parameters (Å, º) top
C25—C261.387 (4)C6—H610.987
C25—O311.368 (3)N7—C81.402 (3)
C25—C241.408 (4)N7—C111.400 (3)
C26—C271.388 (4)C8—C91.475 (4)
C26—H2610.948C8—O121.219 (3)
C27—C221.383 (4)C9—C101.392 (3)
C27—H2710.955C9—C141.389 (4)
O31—C321.428 (4)C10—C111.478 (4)
C32—H3230.977C10—C171.377 (4)
C32—H3220.979C11—O131.216 (3)
C32—H3210.980C14—C151.397 (4)
O33—C341.367 (5)C14—N181.398 (3)
O33—H3310.877C15—C161.395 (4)
C34—C351.438 (6)C15—H1510.940
C34—C361.336 (6)C16—C171.392 (4)
C35—C35i1.338 (9)C16—H1610.966
C35—H3510.940C17—H1710.933
C36—C36i1.509 (9)N18—C191.367 (3)
C36—C371.409 (8)N18—H1810.860
C37—O381.364 (8)C19—C201.509 (4)
C37—O391.226 (8)C19—O211.218 (3)
O38—O38i1.829 (13)C20—H2010.955
O38—H3810.853C20—H2020.986
S1—O21.447 (2)C20—H2030.969
S1—O31.444 (2)C22—C231.399 (4)
S1—C41.756 (3)C23—C241.389 (4)
S1—C51.772 (3)C23—H2310.958
C4—H410.963C24—O281.371 (3)
C4—H420.953C30—C291.508 (4)
C4—H430.974C30—H3010.950
C5—C61.529 (3)C30—H3020.950
C5—H520.979C30—H3030.950
C5—H510.986C29—O281.444 (3)
C6—N71.473 (3)C29—H2910.950
C6—C221.515 (4)C29—H2920.950
C26—C25—O31125.1 (3)N7—C8—C9106.6 (2)
C26—C25—C24119.3 (2)N7—C8—O12124.3 (2)
O31—C25—C24115.6 (3)C9—C8—O12129.2 (2)
C25—C26—C27120.3 (2)C8—C9—C10108.3 (2)
C25—C26—H261119.4C8—C9—C14130.0 (2)
C27—C26—H261120.4C10—C9—C14121.7 (2)
C26—C27—C22121.1 (3)C9—C10—C11107.7 (2)
C26—C27—H271120.8C9—C10—C17122.0 (3)
C22—C27—H271118.1C11—C10—C17130.3 (2)
C25—O31—C32115.8 (2)C10—C11—N7106.8 (2)
O31—C32—H323103.7C10—C11—O13128.9 (2)
O31—C32—H322108.0N7—C11—O13124.3 (3)
H323—C32—H322111.2C9—C14—C15116.8 (2)
O31—C32—H321110.6C9—C14—N18118.2 (2)
H323—C32—H321110.7C15—C14—N18125.1 (2)
H322—C32—H321112.4C14—C15—C16120.8 (3)
C34—O33—H331116.1C14—C15—H151119.9
O33—C34—C35118.7 (4)C16—C15—H151119.3
O33—C34—C36118.0 (4)C15—C16—C17122.2 (3)
C35—C34—C36123.3 (4)C15—C16—H161118.3
C34—C35—C35i119.2 (3)C17—C16—H161119.5
C34—C35—H351119.9C16—C17—C10116.5 (3)
C35i—C35—H351120.8C16—C17—H171121.4
C36i—C36—C34117.5 (3)C10—C17—H171122.1
C36i—C36—C37113.5 (4)C14—N18—C19128.3 (2)
C34—C36—C37127.5 (5)C14—N18—H181114.6
C36—C37—O38122.9 (6)C19—N18—H181117.1
C36—C37—O39121.7 (6)N18—C19—C20113.9 (2)
O38—C37—O39115.4 (6)N18—C19—O21123.6 (3)
C37—O38—O38i96.5 (5)C20—C19—O21122.5 (2)
C37—O38—H381106.4C19—C20—H201109.7
O38i—O38—H381117.8C19—C20—H202111.6
O2—S1—O3117.61 (12)H201—C20—H202107.9
O2—S1—C4107.76 (14)C19—C20—H203108.9
O3—S1—C4109.52 (15)H201—C20—H203109.1
O2—S1—C5108.99 (12)H202—C20—H203109.6
O3—S1—C5109.13 (12)C6—C22—C27118.5 (2)
C4—S1—C5102.81 (13)C6—C22—C23122.6 (2)
S1—C4—H41108.2C27—C22—C23118.9 (2)
S1—C4—H42106.0C22—C23—C24120.6 (2)
H41—C4—H42110.2C22—C23—H231118.3
S1—C4—H43110.0C24—C23—H231121.0
H41—C4—H43109.8C25—C24—C23119.8 (2)
H42—C4—H43112.5C25—C24—O28115.4 (2)
S1—C5—C6113.62 (17)C23—C24—O28124.8 (2)
S1—C5—H52103.3C29—C30—H301109.7
C6—C5—H52110.2C29—C30—H302109.6
S1—C5—H51106.6H301—C30—H302109.5
C6—C5—H51111.2C29—C30—H303109.1
H52—C5—H51111.7H301—C30—H303109.5
C5—C6—N7111.0 (2)H302—C30—H303109.5
C5—C6—C22111.6 (2)C30—C29—O28107.3 (3)
N7—C6—C22112.4 (2)C30—C29—H291110.6
C5—C6—H61105.7O28—C29—H291110.2
N7—C6—H61105.6C30—C29—H292109.3
C22—C6—H61110.1O28—C29—H292110.0
C6—N7—C8123.7 (2)H291—C29—H292109.5
C6—N7—C11125.5 (2)C29—O28—C24117.0 (2)
C8—N7—C11110.6 (2)
Symmetry code: (i) y+1, x+1, z+3/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C26—H261···O3ii0.952.433.365 (4)168
C27—H271···O2ii0.962.533.256 (4)133
C4—H42···O12iii0.952.383.038 (4)126
C4—H43···O2iv0.972.493.339 (4)146
C5—H52···O21ii0.982.473.432 (4)166
C5—H51···O13iv0.992.303.153 (4)144
C15—H151···O210.942.292.887 (4)121
C23—H231···O13iv0.962.443.399 (4)179
N18—H181···O120.862.292.977 (4)138
O38—H381···O31v0.852.272.976 (4)140
O33—H331···O390.881.992.664 (4)133
Symmetry codes: (ii) x+3/2, y1/2, z+5/4; (iii) y+1/2, x+3/2, z1/4; (iv) y, x, z+1; (v) x+1/2, y+1/2, z+5/4.
(Apremilast_4_hydroxybenzoic_acid) top
Crystal data top
C25.50H25.50N2O8.50SDx = 1.429 Mg m3
Mr = 528.06Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 42651 reflections
a = 12.9076 (1) Åθ = 4–67°
c = 29.4670 (2) ŵ = 1.66 mm1
V = 4909.38 (8) Å3T = 120 K
Z = 8Block, colorless
F(000) = 22120.27 × 0.14 × 0.12 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4320 reflections with I > 2.0σ(I)
Focussing mirrors monochromatorRint = 0.042
ω scansθmax = 67.8°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro (Rigaku Oxford Diffraction, 2017)
h = 1515
Tmin = 0.59, Tmax = 0.82k = 1515
84206 measured reflectionsl = 3435
4433 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.050 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.08P)2 + 7.51P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.146(Δ/σ)max = 0.002
S = 1.03Δρmax = 0.70 e Å3
4433 reflectionsΔρmin = 0.86 e Å3
356 parametersAbsolute structure: Parsons, Flack & Wagner (2013), 1790 Friedel Pairs
62 restraintsAbsolute structure parameter: 0.000 (3)
Primary atom site location: other
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.16345 (7)0.59577 (7)0.71378 (3)0.0259
O20.0761 (2)0.5544 (2)0.68929 (9)0.0348
O30.2117 (2)0.6883 (2)0.69586 (9)0.0331
C40.1252 (3)0.6203 (3)0.76999 (14)0.0402
C50.2590 (3)0.4986 (3)0.71999 (11)0.0245
C60.2971 (3)0.4542 (3)0.67499 (11)0.0227
C70.3061 (3)0.5631 (3)0.60378 (11)0.0223
C80.3679 (3)0.6541 (3)0.58890 (11)0.0231
C90.4391 (3)0.6770 (3)0.62254 (11)0.0248
C100.4245 (3)0.6011 (3)0.65965 (11)0.0240
O110.23506 (18)0.51937 (19)0.58418 (8)0.0267
O120.47155 (19)0.5941 (2)0.69558 (8)0.0292
C130.3636 (3)0.7094 (3)0.54847 (11)0.0235
C140.4344 (3)0.7913 (3)0.54412 (13)0.0282
C150.5040 (3)0.8140 (3)0.57841 (13)0.0315
C160.5091 (3)0.7566 (3)0.61870 (12)0.0291
N170.2920 (2)0.6786 (2)0.51553 (10)0.0256
C180.2750 (3)0.7198 (3)0.47330 (12)0.0270
C190.2013 (3)0.6583 (3)0.44478 (12)0.0346
O200.3171 (2)0.7983 (2)0.45987 (8)0.0339
C210.3689 (3)0.3617 (3)0.68219 (12)0.0249
C220.4241 (3)0.3472 (3)0.72271 (12)0.0253
C230.4873 (3)0.2616 (3)0.72880 (12)0.0266
C240.4964 (3)0.1874 (3)0.69337 (13)0.0297
C250.4427 (3)0.2028 (3)0.65355 (13)0.0313
C260.3786 (3)0.2891 (3)0.64816 (12)0.0284
O270.5446 (2)0.2416 (2)0.76702 (9)0.0346
C280.5407 (3)0.3192 (3)0.80235 (13)0.0359
C290.6180 (4)0.2899 (4)0.83835 (17)0.0566
O300.5596 (2)0.1046 (2)0.70251 (10)0.0376
C310.5765 (4)0.0347 (4)0.66559 (16)0.0550
C360.4749 (8)0.5318 (8)0.0446 (4)0.1352
C370.5577 (7)0.5855 (6)0.0219 (3)0.1129
N60.3445 (2)0.5345 (2)0.64627 (9)0.0221
H420.31830.52970.73530.0272*
H410.22990.44330.73850.0271*
H510.23720.42820.65830.0253*
H1420.17750.69950.41980.0500*
H1410.14350.63750.46330.0502*
H1430.23600.59760.43420.0502*
H1510.43450.83120.51770.0332*
H1610.54940.86960.57420.0340*
H1710.55770.77210.64110.0341*
H2210.34310.29750.62060.0309*
H2310.44830.15540.62980.0329*
H2610.61980.02120.67620.0759*
H2630.60900.06980.64060.0760*
H2620.51090.00660.65600.0761*
H2810.41890.39680.74570.0281*
H3020.47230.32410.81520.0432*
H3010.55980.38590.78950.0430*
H3110.62350.34600.85960.0831*
H3130.59410.22820.85340.0831*
H3120.68440.27640.82420.0830*
H3210.17970.64690.78840.0571*
H3230.06910.66910.76980.0569*
H3220.09970.55720.78310.0571*
H1110.253 (4)0.635 (4)0.5211 (14)0.0297*
O380.5951 (12)0.6724 (11)0.0394 (6)0.19110.5000
C350.4281 (7)0.4543 (8)0.0208 (3)0.1418
C340.3418 (12)0.4012 (13)0.0397 (6)0.17520.5000
O330.2852 (14)0.3291 (15)0.0124 (8)0.19700.5000
O390.3048 (15)0.4311 (15)0.0793 (9)0.22070.5000
H3710.59340.63910.03710.1482*0.5000
H3610.46280.55500.07470.1769*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0259 (4)0.0280 (4)0.0239 (4)0.0048 (3)0.0027 (3)0.0006 (3)
O20.0293 (13)0.0354 (14)0.0398 (15)0.0033 (11)0.0038 (11)0.0001 (12)
O30.0376 (14)0.0290 (13)0.0328 (13)0.0020 (11)0.0019 (11)0.0057 (11)
C40.044 (2)0.044 (2)0.032 (2)0.0053 (18)0.0152 (17)0.0055 (17)
C50.0261 (17)0.0267 (17)0.0207 (15)0.0025 (13)0.0008 (13)0.0021 (13)
C60.0236 (16)0.0249 (16)0.0196 (15)0.0008 (14)0.0011 (13)0.0021 (13)
C70.0219 (16)0.0261 (17)0.0189 (15)0.0011 (13)0.0002 (13)0.0024 (13)
C80.0225 (16)0.0238 (16)0.0230 (16)0.0037 (13)0.0009 (13)0.0058 (13)
C90.0230 (16)0.0270 (17)0.0243 (16)0.0029 (13)0.0019 (13)0.0063 (14)
C100.0229 (17)0.0259 (17)0.0231 (17)0.0024 (14)0.0001 (13)0.0056 (14)
O110.0275 (13)0.0297 (13)0.0229 (11)0.0051 (10)0.0049 (10)0.0017 (10)
O120.0266 (13)0.0385 (14)0.0224 (12)0.0004 (11)0.0063 (10)0.0036 (11)
C130.0211 (16)0.0247 (17)0.0245 (17)0.0026 (13)0.0003 (13)0.0040 (13)
C140.0265 (18)0.0253 (17)0.0330 (19)0.0031 (14)0.0007 (14)0.0006 (14)
C150.0277 (18)0.0273 (19)0.040 (2)0.0061 (15)0.0038 (15)0.0021 (16)
C160.0255 (17)0.0321 (19)0.0298 (18)0.0004 (15)0.0055 (14)0.0051 (15)
N170.0278 (15)0.0226 (15)0.0265 (15)0.0064 (12)0.0051 (12)0.0017 (12)
C180.0274 (17)0.0305 (19)0.0233 (17)0.0054 (15)0.0022 (14)0.0014 (14)
C190.042 (2)0.037 (2)0.0251 (17)0.0018 (18)0.0072 (16)0.0015 (16)
O200.0390 (15)0.0344 (14)0.0284 (13)0.0054 (12)0.0005 (11)0.0051 (11)
C210.0237 (17)0.0257 (18)0.0253 (16)0.0030 (14)0.0009 (13)0.0011 (13)
C220.0253 (17)0.0242 (17)0.0265 (17)0.0008 (13)0.0019 (13)0.0047 (14)
C230.0251 (17)0.0215 (16)0.0332 (18)0.0001 (13)0.0013 (14)0.0015 (14)
C240.0252 (18)0.0242 (17)0.040 (2)0.0020 (14)0.0068 (15)0.0004 (15)
C250.034 (2)0.0275 (18)0.0319 (18)0.0024 (15)0.0076 (15)0.0055 (15)
C260.0314 (19)0.0293 (18)0.0243 (17)0.0034 (14)0.0024 (14)0.0036 (14)
O270.0353 (14)0.0288 (13)0.0397 (14)0.0040 (11)0.0114 (12)0.0031 (11)
C280.045 (2)0.0247 (18)0.0380 (19)0.0012 (16)0.0156 (18)0.0021 (16)
C290.075 (4)0.039 (2)0.056 (3)0.011 (2)0.033 (3)0.005 (2)
O300.0416 (15)0.0261 (13)0.0450 (16)0.0112 (12)0.0070 (13)0.0024 (12)
C310.086 (4)0.035 (2)0.043 (2)0.022 (2)0.031 (2)0.0048 (19)
C360.119 (5)0.113 (5)0.174 (7)0.054 (4)0.022 (5)0.047 (5)
C370.104 (4)0.083 (4)0.152 (7)0.021 (4)0.045 (4)0.036 (4)
N60.0225 (13)0.0254 (14)0.0183 (13)0.0006 (11)0.0023 (11)0.0029 (11)
O380.192 (10)0.150 (8)0.231 (11)0.007 (9)0.034 (9)0.007 (9)
C350.104 (5)0.109 (5)0.212 (9)0.027 (5)0.057 (5)0.073 (5)
C340.144 (8)0.149 (8)0.233 (12)0.005 (8)0.049 (8)0.067 (8)
O330.179 (9)0.177 (9)0.235 (14)0.004 (10)0.046 (8)0.050 (8)
O390.195 (11)0.198 (11)0.269 (14)0.008 (11)0.045 (11)0.037 (11)
Geometric parameters (Å, º) top
S1—O21.441 (3)C19—H1430.955
S1—O31.447 (3)C21—C221.403 (5)
S1—C41.757 (4)C21—C261.378 (5)
S1—C51.768 (3)C22—C231.385 (5)
C4—H3210.952C22—H2810.935
C4—H3230.959C23—C241.421 (5)
C4—H3220.959C23—O271.371 (4)
C5—C61.527 (4)C24—C251.377 (6)
C5—H420.975C24—O301.371 (4)
C5—H410.974C25—C261.397 (5)
C6—C211.526 (5)C25—H2310.931
C6—N61.472 (4)C26—H2210.938
C6—H510.977O27—C281.445 (4)
C7—C81.486 (5)C28—C291.505 (6)
C7—O111.222 (4)C28—H3020.962
C7—N61.396 (4)C28—H3010.973
C8—C91.384 (5)C29—H3110.959
C8—C131.390 (5)C29—H3130.962
C9—C101.480 (5)C29—H3120.968
C9—C161.373 (5)O30—C311.430 (5)
C10—O121.224 (4)C31—H2610.965
C10—N61.400 (4)C31—H2630.962
C13—C141.403 (5)C31—H2620.964
C13—N171.398 (4)C36—C371.438 (13)
C14—C151.383 (5)C36—C351.363 (14)
C14—H1510.933C36—H3610.949
C15—C161.401 (5)C37—C37i1.386 (16)
C15—H1610.934C37—O381.327 (8)
C16—H1710.933C37—H3710.946
N17—C181.371 (5)C35—C35i1.32 (2)
N17—H1110.77 (5)C35—C341.421 (9)
C18—C191.497 (5)C34—O331.43 (2)
C18—O201.216 (5)C34—O391.32 (3)
C19—H1420.960O33—O33i1.09 (4)
C19—H1410.963
O2—S1—O3117.40 (16)H141—C19—H143108.6
O2—S1—C4108.6 (2)C6—C21—C22122.1 (3)
O3—S1—C4108.41 (19)C6—C21—C26119.1 (3)
O2—S1—C5109.53 (16)C22—C21—C26118.8 (3)
O3—S1—C5108.85 (16)C21—C22—C23121.1 (3)
C4—S1—C5103.07 (18)C21—C22—H281119.2
S1—C4—H321113.2C23—C22—H281119.7
S1—C4—H323108.9C22—C23—C24119.4 (3)
H321—C4—H323109.0C22—C23—O27125.0 (3)
S1—C4—H322108.8C24—C23—O27115.6 (3)
H321—C4—H322109.3C23—C24—C25119.2 (3)
H323—C4—H322107.5C23—C24—O30115.4 (3)
S1—C5—C6113.7 (2)C25—C24—O30125.4 (3)
S1—C5—H42107.7C24—C25—C26120.7 (3)
C6—C5—H42107.6C24—C25—H231120.4
S1—C5—H41108.0C26—C25—H231119.0
C6—C5—H41109.6C25—C26—C21120.9 (3)
H42—C5—H41110.3C25—C26—H221118.7
C5—C6—C21111.7 (3)C21—C26—H221120.4
C5—C6—N6111.6 (3)C23—O27—C28116.3 (3)
C21—C6—N6112.3 (3)O27—C28—C29108.1 (3)
C5—C6—H51108.1O27—C28—H302111.1
C21—C6—H51106.4C29—C28—H302110.4
N6—C6—H51106.4O27—C28—H301108.9
C8—C7—O11128.9 (3)C29—C28—H301109.2
C8—C7—N6106.4 (3)H302—C28—H301109.1
O11—C7—N6124.6 (3)C28—C29—H311108.6
C7—C8—C9108.3 (3)C28—C29—H313108.6
C7—C8—C13129.6 (3)H311—C29—H313110.5
C9—C8—C13122.1 (3)C28—C29—H312109.2
C8—C9—C10107.7 (3)H311—C29—H312110.5
C8—C9—C16122.5 (3)H313—C29—H312109.4
C10—C9—C16129.8 (3)C24—O30—C31115.7 (3)
C9—C10—O12128.7 (3)O30—C31—H261108.2
C9—C10—N6107.0 (3)O30—C31—H263110.7
O12—C10—N6124.4 (3)H261—C31—H263110.4
C8—C13—C14116.0 (3)O30—C31—H262109.1
C8—C13—N17118.4 (3)H261—C31—H262108.8
C14—C13—N17125.6 (3)H263—C31—H262109.6
C13—C14—C15121.1 (3)C37—C36—C35116.3 (9)
C13—C14—H151119.5C37—C36—H361113.9
C15—C14—H151119.4C35—C36—H361129.7
C14—C15—C16122.5 (3)C36—C37—C37i120.0 (5)
C14—C15—H161118.2C36—C37—O38119.8 (2)
C16—C15—H161119.3C37i—C37—O38119.1 (6)
C15—C16—C9115.8 (3)C36—C37—H371119.6
C15—C16—H171121.3C37i—C37—H371120.3
C9—C16—H171123.0O38—C37—H37110.9
C13—N17—C18128.7 (3)C6—N6—C10125.2 (3)
C13—N17—H111119 (3)C6—N6—C7123.7 (3)
C18—N17—H111112 (3)C10—N6—C7110.6 (3)
N17—C18—C19113.9 (3)C36—C35—C35i123.6 (6)
N17—C18—O20123.2 (3)C36—C35—C34120.0 (7)
C19—C18—O20122.9 (3)C35i—C35—C34116.2 (5)
C18—C19—H142110.0C35—C34—O33119.7 (8)
C18—C19—H141108.8C35—C34—O39119.2 (5)
H142—C19—H141110.0O33—C34—O39120.2 (2)
C18—C19—H143108.7C34—O33—O33i116.9 (14)
H142—C19—H143110.7
Symmetry code: (i) y, x, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H42···O120.982.443.093 (7)124
C5—H42···O12ii0.982.333.152 (7)141
C5—H41···O20iii0.972.493.453 (7)171
C14—H151···O200.932.322.910 (7)121
C26—H221···O3iii0.942.523.276 (7)138
C26—H221···O38iv0.942.553.261 (7)132
C25—H231···O2iii0.932.443.349 (7)165
C31—H261···O20v0.972.543.493 (7)169
C22—H281···O12ii0.942.433.366 (7)179
C4—H321···O3ii0.952.543.392 (7)149
C4—H323···O11vi0.962.373.042 (7)126
N17—H111···O110.7702.3962.976 (7)133 (4)
Symmetry codes: (ii) y+1, x+1, z+3/2; (iii) x+1/2, y1/2, z+5/4; (iv) x+1, y+1, z+1/2; (v) y+3/2, x1/2, z+1/4; (vi) y+1/2, x+1/2, z+1/4.
(apremilastanisol) top
Crystal data top
C25.50H28.00N2O7.50SDx = 1.394 Mg m3
Mr = 514.58Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 39017 reflections
a = 12.8885 (1) Åθ = 4–67°
c = 29.5227 (1) ŵ = 1.62 mm1
V = 4904.12 (8) Å3T = 120 K
Z = 8Block, colorless
F(000) = 2167.9880.22 × 0.21 × 0.14 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4342 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.031
ω scansθmax = 67.6°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.15, Tmax = 0.80k = 1515
61003 measured reflectionsl = 3535
4440 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 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(F2) = 0.046(Δ/σ)max = 0.003
S = 1.10Δρmax = 0.76 e Å3
4440 reflectionsΔρmin = 0.35 e Å3
333 parametersAbsolute structure: Flack (1983), 1823 Friedel-pairs
8 restraintsAbsolute structure parameter: 0.010 (16)
Primary atom site location: structure-invariant direct methods
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.40256 (4)0.16203 (4)0.463269 (18)0.0232
O20.31052 (12)0.21085 (12)0.44540 (5)0.0294
O30.44436 (12)0.07517 (12)0.43880 (5)0.0319
C40.37759 (19)0.12371 (19)0.51958 (7)0.0342
C50.50031 (16)0.25750 (16)0.47003 (6)0.0211
C60.54509 (16)0.29622 (16)0.42514 (6)0.0201
N70.46407 (13)0.34358 (13)0.39649 (5)0.0194
C80.43542 (15)0.30528 (16)0.35393 (6)0.0189
C90.34475 (16)0.36737 (15)0.33910 (7)0.0192
C100.32183 (16)0.43851 (16)0.37257 (7)0.0210
C110.39785 (16)0.42352 (15)0.41017 (7)0.0200
O120.47862 (11)0.23406 (11)0.33434 (4)0.0238
O130.40403 (12)0.46926 (11)0.44562 (5)0.0257
C140.28966 (16)0.36325 (15)0.29875 (7)0.0207
C150.20800 (16)0.43430 (16)0.29406 (7)0.0240
C160.18482 (17)0.50396 (17)0.32862 (7)0.0279
C170.24149 (17)0.50854 (17)0.36869 (7)0.0254
N180.32062 (13)0.29195 (13)0.26578 (5)0.0220
C190.28006 (17)0.27599 (17)0.22352 (7)0.0239
C200.34240 (18)0.20240 (18)0.19486 (7)0.0301
O210.20137 (11)0.31796 (12)0.21001 (5)0.0299
C220.63718 (16)0.36884 (16)0.43235 (7)0.0208
C230.65132 (16)0.42295 (16)0.47321 (7)0.0219
C240.73707 (16)0.48613 (16)0.47911 (7)0.0225
C250.81033 (17)0.49640 (17)0.44397 (7)0.0252
C260.79545 (17)0.44337 (17)0.40400 (7)0.0267
C270.70926 (16)0.37950 (17)0.39837 (7)0.0241
O280.75666 (12)0.54271 (12)0.51777 (5)0.0290
C290.67935 (17)0.53842 (19)0.55282 (7)0.0311
C300.7105 (2)0.6129 (2)0.58952 (9)0.0508
O310.89353 (12)0.55971 (12)0.45321 (5)0.0326
C320.96278 (19)0.5778 (2)0.41645 (8)0.0484
O401.1500 (4)1.1031 (4)0.0325 (2)0.10580.5000
C411.1917 (3)1.1917 (3)0.000000 (10)0.1315
C421.0686 (3)1.0398 (3)0.02287 (16)0.1111
C431.0150 (4)0.9624 (4)0.04385 (16)0.1049
C440.9384 (3)0.9125 (2)0.02191 (11)0.0636
H2010.30720.18560.16860.0451*
H2030.40610.23830.18630.0460*
H2020.36120.14240.21170.0451*
H1510.16650.43510.26700.0289*
H1610.12940.55170.32400.0327*
H1710.22830.55420.39200.0307*
H3030.65950.61430.61350.0750*
H3010.77700.59640.60200.0746*
H3020.71440.68160.57720.0737*
H2910.67510.46560.56590.0365*
H2920.60950.55710.54020.0371*
H3211.01710.62210.42860.0719*
H3230.99510.51280.40680.0728*
H3220.93020.60900.39090.0729*
H2710.70070.34320.37070.0279*
H2610.84430.44950.38050.0308*
H2310.60190.41670.49690.0252*
H610.57060.23610.40850.0235*
H520.55380.22560.48870.0244*
H510.46980.31570.48660.0236*
H420.35480.18430.53650.0501*
H410.44220.09270.53190.0510*
H430.32030.07210.51730.0500*
H4410.89890.85910.03690.0781*
H4311.03340.94560.07340.1265*
H1810.37340.25390.27390.0315*
H4141.24881.22540.01400.1514*0.5000
H4161.13811.24070.00550.1514*0.5000
H4151.21341.16200.02790.1514*0.5000
H4211.12381.07440.03790.1287*0.5000
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0245 (3)0.0241 (3)0.0210 (2)0.0049 (2)0.0014 (2)0.0018 (2)
O20.0249 (8)0.0348 (9)0.0286 (8)0.0028 (7)0.0045 (7)0.0034 (7)
O30.0356 (9)0.0255 (9)0.0346 (9)0.0048 (7)0.0011 (7)0.0040 (7)
C40.0387 (15)0.0371 (14)0.0267 (12)0.0062 (10)0.0024 (11)0.0093 (10)
C50.0225 (11)0.0230 (11)0.0178 (10)0.0034 (8)0.0014 (9)0.0008 (9)
C60.0229 (11)0.0205 (11)0.0170 (10)0.0013 (9)0.0003 (9)0.0013 (9)
N70.0202 (9)0.0203 (9)0.0177 (8)0.0001 (7)0.0013 (7)0.0015 (7)
C80.0197 (11)0.0205 (11)0.0166 (9)0.0022 (8)0.0030 (8)0.0008 (8)
C90.0205 (11)0.0180 (10)0.0193 (10)0.0019 (8)0.0039 (9)0.0008 (8)
C100.0223 (11)0.0196 (11)0.0213 (10)0.0037 (8)0.0039 (9)0.0002 (8)
C110.0205 (11)0.0189 (11)0.0205 (10)0.0013 (9)0.0041 (9)0.0003 (9)
O120.0251 (8)0.0254 (8)0.0210 (7)0.0043 (6)0.0019 (6)0.0033 (6)
O130.0328 (9)0.0251 (8)0.0193 (7)0.0006 (7)0.0019 (7)0.0061 (6)
C140.0200 (11)0.0210 (11)0.0212 (11)0.0032 (9)0.0034 (9)0.0007 (8)
C150.0226 (11)0.0242 (12)0.0253 (11)0.0006 (9)0.0008 (9)0.0017 (9)
C160.0229 (12)0.0240 (12)0.0369 (13)0.0037 (10)0.0001 (10)0.0010 (10)
C170.0284 (12)0.0224 (12)0.0255 (11)0.0026 (10)0.0058 (9)0.0037 (9)
N180.0212 (9)0.0245 (10)0.0203 (9)0.0029 (8)0.0013 (7)0.0027 (8)
C190.0262 (12)0.0243 (12)0.0211 (11)0.0065 (9)0.0023 (9)0.0011 (9)
C200.0333 (13)0.0350 (13)0.0220 (11)0.0015 (11)0.0006 (10)0.0067 (10)
O210.0296 (9)0.0356 (9)0.0244 (8)0.0043 (7)0.0064 (7)0.0002 (7)
C220.0203 (11)0.0217 (11)0.0205 (10)0.0019 (9)0.0006 (8)0.0015 (8)
C230.0208 (11)0.0222 (11)0.0227 (10)0.0003 (8)0.0047 (9)0.0002 (9)
C240.0219 (11)0.0217 (11)0.0239 (10)0.0010 (8)0.0006 (9)0.0014 (9)
C250.0205 (11)0.0263 (12)0.0289 (11)0.0007 (9)0.0002 (9)0.0061 (10)
C260.0218 (12)0.0323 (13)0.0259 (11)0.0016 (9)0.0040 (10)0.0045 (10)
C270.0267 (12)0.0261 (12)0.0195 (10)0.0039 (9)0.0014 (9)0.0001 (9)
O280.0268 (8)0.0305 (9)0.0296 (8)0.0053 (7)0.0020 (7)0.0087 (7)
C290.0247 (12)0.0396 (14)0.0289 (11)0.0011 (11)0.0024 (10)0.0112 (11)
C300.0380 (16)0.072 (2)0.0425 (15)0.0098 (14)0.0061 (13)0.0269 (15)
O310.0249 (8)0.0380 (9)0.0350 (9)0.0114 (7)0.0003 (7)0.0046 (7)
C320.0299 (14)0.081 (2)0.0345 (14)0.0232 (14)0.0057 (11)0.0229 (14)
O400.072 (4)0.080 (4)0.166 (6)0.012 (3)0.011 (4)0.054 (4)
C410.091 (3)0.091 (3)0.213 (9)0.050 (4)0.056 (4)0.056 (4)
C420.039 (2)0.071 (3)0.224 (6)0.004 (2)0.035 (3)0.088 (3)
C430.089 (3)0.114 (4)0.111 (4)0.063 (3)0.015 (3)0.059 (3)
C440.058 (2)0.0409 (17)0.092 (2)0.0093 (15)0.0241 (18)0.0159 (18)
Geometric parameters (Å, º) top
S1—O21.4427 (16)C22—C271.374 (3)
S1—O31.4371 (16)C23—C241.384 (3)
S1—C41.764 (2)C23—H2310.950
S1—C51.772 (2)C24—C251.409 (3)
C4—H420.973C24—O281.378 (2)
C4—H410.993C25—C261.377 (3)
C4—H430.996C25—O311.375 (3)
C5—C61.529 (3)C26—C271.393 (3)
C5—H520.974C26—H2610.939
C5—H510.978C27—H2710.948
C6—N71.476 (2)O28—C291.438 (2)
C6—C221.526 (3)C29—C301.502 (3)
C6—H610.976C29—H2911.016
N7—C81.400 (2)C29—H2921.004
N7—C111.397 (3)C30—H3030.967
C8—C91.482 (3)C30—H3010.956
C8—O121.219 (2)C30—H3020.958
C9—C101.380 (3)O31—C321.424 (3)
C9—C141.388 (3)C32—H3210.971
C10—C111.493 (3)C32—H3230.978
C10—C171.378 (3)C32—H3220.953
C11—O131.204 (2)O40—C411.584 (7)
C14—C151.402 (3)O40—C421.359 (6)
C14—N181.397 (3)C41—H415i0.950
C15—C161.391 (3)C41—H416i0.950
C15—H1510.962C41—H414i0.950
C16—C171.392 (3)C41—H4140.950
C16—H1610.953C41—H4160.950
C17—H1710.921C41—H4150.950
N18—C191.368 (3)C42—C42i1.449 (10)
N18—H1810.872C42—C431.363 (6)
C19—C201.504 (3)C42—H4210.950
C19—O211.217 (3)C43—C441.344 (5)
C20—H2010.924C43—H4310.929
C20—H2030.976C44—C44i1.377 (7)
C20—H2020.951C44—H4410.964
C22—C231.405 (3)
O2—S1—O3117.66 (9)C25—C24—O28115.94 (18)
O2—S1—C4108.46 (11)C24—C25—C26119.4 (2)
O3—S1—C4108.90 (11)C24—C25—O31115.61 (19)
O2—S1—C5108.84 (10)C26—C25—O31125.0 (2)
O3—S1—C5109.32 (10)C25—C26—C27120.5 (2)
C4—S1—C5102.59 (10)C25—C26—H261119.8
S1—C4—H42108.4C27—C26—H261119.8
S1—C4—H41107.7C26—C27—C22120.7 (2)
H42—C4—H41112.9C26—C27—H271119.2
S1—C4—H43104.9C22—C27—H271120.1
H42—C4—H43110.4C24—O28—C29116.67 (16)
H41—C4—H43112.2O28—C29—C30108.01 (19)
S1—C5—C6113.40 (13)O28—C29—H291110.2
S1—C5—H52105.9C30—C29—H291109.3
C6—C5—H52111.2O28—C29—H292110.1
S1—C5—H51107.6C30—C29—H292110.8
C6—C5—H51109.6H291—C29—H292108.3
H52—C5—H51109.0C29—C30—H303111.0
C5—C6—N7111.39 (17)C29—C30—H301112.1
C5—C6—C22111.88 (16)H303—C30—H301109.3
N7—C6—C22112.12 (16)C29—C30—H302109.3
C5—C6—H61107.8H303—C30—H302107.2
N7—C6—H61106.1H301—C30—H302107.8
C22—C6—H61107.2C25—O31—C32115.75 (18)
C6—N7—C8123.73 (16)O31—C32—H321105.5
C6—N7—C11124.84 (16)O31—C32—H323110.4
C8—N7—C11111.00 (16)H321—C32—H323107.7
N7—C8—C9106.42 (16)O31—C32—H322113.3
N7—C8—O12124.81 (18)H321—C32—H322111.2
C9—C8—O12128.77 (18)H323—C32—H322108.6
C8—C9—C10108.41 (18)C41—O40—C42124.6 (6)
C8—C9—C14129.51 (18)O40—C41—O40i83.0 (5)
C10—C9—C14122.04 (19)O40—C41—H415i63.4
C9—C10—C11107.81 (17)O40i—C41—H415i109.5
C9—C10—C17122.43 (19)O40—C41—H416i66.3
C11—C10—C17129.76 (19)O40i—C41—H416i109.7
C10—C11—N7106.33 (16)H415i—C41—H416i109.5
C10—C11—O13128.77 (19)O40—C41—H414i167.7
N7—C11—O13124.9 (2)O40i—C41—H414i109.2
C9—C14—C15116.35 (19)H415i—C41—H414i109.5
C9—C14—N18118.50 (18)H416i—C41—H414i109.5
C15—C14—N18125.13 (19)O40—C41—H414109.2
C14—C15—C16120.7 (2)O40i—C41—H414167.7
C14—C15—H151120.4H415i—C41—H41478.4
C16—C15—H151118.9H416i—C41—H41475.0
C15—C16—C17122.5 (2)H414i—C41—H41458.7
C15—C16—H161118.2O40—C41—H416109.7
C17—C16—H161119.2O40i—C41—H41666.3
C16—C17—C10115.9 (2)H415i—C41—H41670.1
C16—C17—H171124.4H416i—C41—H416175.0
C10—C17—H171119.6H414i—C41—H41675.0
C14—N18—C19128.69 (18)O40—C41—H415109.5
C14—N18—H181113.7O40i—C41—H41563.4
C19—N18—H181117.6H415i—C41—H415171.3
N18—C19—C20113.82 (19)H416i—C41—H41570.1
N18—C19—O21123.4 (2)H414i—C41—H41578.4
C20—C19—O21122.77 (19)H414—C41—H416109.5
C19—C20—H201111.0H414—C41—H415109.5
C19—C20—H203107.2H416—C41—H415109.5
H201—C20—H203107.9C42i—C42—O40103.8 (4)
C19—C20—H202110.9C42i—C42—C43118.8 (3)
H201—C20—H202111.9O40—C42—C43137.4 (6)
H203—C20—H202107.8C42i—C42—H421120.6
C6—C22—C23121.66 (18)O40—C42—H42116.8
C6—C22—C27119.02 (18)C43—C42—H421120.7
C23—C22—C27119.30 (19)C42—C43—C44120.2 (5)
C22—C23—C24120.25 (19)C42—C43—H431117.9
C22—C23—H231120.3C44—C43—H431121.9
C24—C23—H231119.5C44i—C44—C43121.0 (3)
C23—C24—C25119.86 (19)C44i—C44—H441118.5
C23—C24—O28124.20 (19)C43—C44—H441120.5
Symmetry code: (i) y, x, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C32—H321···O21ii0.972.533.490 (3)167
C27—H271···O2iii0.952.513.275 (3)138
C26—H261···O3iii0.942.443.354 (3)164
C23—H231···O13iv0.952.413.363 (3)177
C5—H52···O21iii0.972.493.454 (3)168
C5—H51···O130.982.473.084 (3)120
C5—H51···O13iv0.982.303.151 (3)145
C4—H42···O2iv0.972.533.389 (3)148
N18—H181···O120.872.262.967 (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) top
Crystal data top
C25H26.50Br0.50N2O7SDx = 1.465 Mg m3
Mr = 539.01Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 55255 reflections
a = 12.8625 (1) Åθ = 4–68°
c = 29.5499 (1) ŵ = 2.55 mm1
V = 4888.85 (8) Å3T = 120 K
Z = 8Block, colorless
F(000) = 22400.22 × 0.17 × 0.09 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4321 reflections with I > 2.0σ(I)
Focussing mirrors monochromatorRint = 0.033
ω scansθmax = 67.6°, θmin = 3.8°
Absorption correction: multi-scan
CrysAlisPro (Rigaku Oxford Diffraction, 2017)
h = 1515
Tmin = 0.67, Tmax = 0.79k = 1515
92129 measured reflectionsl = 3534
4425 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.074 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.15P)2 + 15.58P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.215(Δ/σ)max = 0.006
S = 0.99Δρmax = 2.25 e Å3
4425 reflectionsΔρmin = 2.35 e Å3
325 parametersAbsolute structure: Parsons, Flack & Wagner (2013), 1780 Friedel Pairs
61 restraintsAbsolute structure parameter: 0.011 (3)
Primary atom site location: structure-invariant direct methods
Special details top

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 (Å2) top
xyzUiso*/Ueq
S10.83868 (10)0.40196 (10)0.71396 (4)0.0198
O20.9262 (3)0.4443 (3)0.68985 (14)0.0269
O30.7907 (3)0.3089 (3)0.69612 (13)0.0267
C40.8756 (5)0.3784 (5)0.7703 (2)0.0307
C50.7433 (4)0.4998 (4)0.72018 (17)0.0192
C60.7045 (4)0.5437 (4)0.67501 (16)0.0192
N70.6574 (3)0.4625 (3)0.64648 (14)0.0180
C80.6953 (4)0.4339 (4)0.60392 (17)0.0178
C90.6322 (4)0.3446 (4)0.58907 (17)0.0172
C100.5610 (4)0.3210 (4)0.62282 (17)0.0185
C110.5758 (4)0.3968 (4)0.65972 (17)0.0183
O120.7671 (3)0.4773 (3)0.58431 (12)0.0215
O130.5299 (3)0.4039 (3)0.69567 (12)0.0232
C140.6354 (4)0.2889 (4)0.54829 (17)0.0196
C150.5644 (4)0.2079 (4)0.54326 (19)0.0238
C160.4939 (4)0.1842 (4)0.57841 (19)0.0249
C170.4904 (4)0.2405 (4)0.61865 (19)0.0226
N180.7073 (4)0.3209 (4)0.51536 (14)0.0209
C190.7227 (4)0.2800 (4)0.47335 (18)0.0219
O200.6815 (3)0.2008 (3)0.45990 (13)0.0283
C210.7980 (5)0.3432 (5)0.44479 (19)0.0293
C220.6315 (4)0.6365 (4)0.68198 (18)0.0191
C230.5778 (4)0.6515 (4)0.72214 (17)0.0198
C240.5134 (4)0.7373 (4)0.72775 (17)0.0195
C250.5036 (4)0.8105 (4)0.69241 (19)0.0224
C260.5571 (4)0.7943 (4)0.65259 (18)0.0213
C270.6207 (4)0.7079 (4)0.64726 (17)0.0198
O280.4569 (3)0.7572 (3)0.76625 (13)0.0259
C290.4606 (5)0.6795 (4)0.80141 (19)0.0275
C300.3818 (6)0.7089 (5)0.8372 (2)0.0418
O310.4410 (3)0.8935 (3)0.70102 (13)0.0259
C320.4271 (5)0.9649 (4)0.6646 (2)0.0307
Br330.58460 (12)0.58460 (12)0.50000.1840
C360.3310 (8)0.3946 (7)0.5364 (3)0.0706
C350.4151 (7)0.4717 (7)0.5375 (3)0.0828
C340.4820 (7)0.4820 (7)0.50000.0917
C370.3281 (7)0.3281 (7)0.50000.0700
H410.89920.44030.78480.0452*
H430.81890.34870.78630.0451*
H520.77390.55440.73730.0201*
H510.68550.47230.73630.0198*
H610.76350.56870.65800.0213*
H1510.56360.16980.51680.0266*
H1610.44810.12870.57470.0271*
H1710.44310.22660.64110.0258*
H2120.81660.30360.41880.0428*
H2110.85910.35820.46270.0428*
H2130.76530.40630.43650.0433*
H2310.58450.60340.74510.0228*
H2610.55030.84270.62950.0253*
H2710.65570.69860.62040.0225*
H2910.52860.67840.81570.0329*
H2920.44210.61150.78860.0330*
H3010.37540.65340.85810.0591*
H3020.40330.77140.85240.0590*
H3030.31630.71900.82380.0588*
H3210.37791.01760.67260.0448*
H3220.49240.99810.65800.0447*
H3230.40360.92940.63810.0446*
H3610.28150.39040.55930.0792*
H3710.27730.27730.50000.0785*
H420.93130.32840.77070.0447*
H3510.42100.51300.56410.0909*
H1810.75020.36720.52400.0246*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0201 (6)0.0204 (6)0.0190 (6)0.0050 (5)0.0022 (5)0.0012 (5)
O20.0213 (19)0.030 (2)0.030 (2)0.0053 (16)0.0044 (16)0.0021 (17)
O30.031 (2)0.0223 (19)0.0266 (19)0.0016 (17)0.0019 (17)0.0043 (16)
C40.035 (3)0.033 (3)0.024 (3)0.005 (3)0.009 (2)0.002 (2)
C50.019 (3)0.020 (2)0.019 (2)0.0044 (19)0.000 (2)0.003 (2)
C60.023 (3)0.021 (3)0.014 (2)0.000 (2)0.0017 (19)0.002 (2)
N70.019 (2)0.021 (2)0.0139 (19)0.0025 (18)0.0045 (17)0.0011 (17)
C80.020 (2)0.016 (2)0.018 (2)0.0006 (19)0.000 (2)0.0030 (19)
C90.019 (2)0.018 (2)0.015 (2)0.0011 (19)0.0004 (19)0.0031 (19)
C100.015 (2)0.021 (3)0.019 (2)0.0047 (19)0.0027 (19)0.005 (2)
C110.015 (2)0.021 (2)0.019 (3)0.001 (2)0.001 (2)0.004 (2)
O120.0230 (19)0.0223 (19)0.0191 (17)0.0023 (15)0.0037 (15)0.0005 (14)
O130.0199 (19)0.030 (2)0.0194 (18)0.0003 (16)0.0052 (15)0.0017 (16)
C140.020 (3)0.021 (3)0.017 (2)0.002 (2)0.002 (2)0.004 (2)
C150.026 (3)0.020 (3)0.026 (3)0.001 (2)0.001 (2)0.002 (2)
C160.021 (3)0.023 (3)0.030 (3)0.003 (2)0.006 (2)0.002 (2)
C170.020 (3)0.022 (3)0.026 (3)0.002 (2)0.005 (2)0.004 (2)
N180.025 (2)0.021 (2)0.016 (2)0.0024 (19)0.0030 (18)0.0024 (17)
C190.025 (3)0.021 (3)0.020 (3)0.004 (2)0.000 (2)0.001 (2)
O200.032 (2)0.029 (2)0.0243 (19)0.0066 (18)0.0029 (17)0.0056 (17)
C210.033 (3)0.035 (3)0.020 (3)0.002 (3)0.004 (2)0.004 (2)
C220.021 (3)0.018 (3)0.019 (2)0.003 (2)0.0001 (19)0.0036 (19)
C230.022 (3)0.020 (2)0.018 (2)0.002 (2)0.001 (2)0.004 (2)
C240.022 (3)0.019 (3)0.017 (2)0.002 (2)0.0018 (19)0.0004 (19)
C250.022 (3)0.019 (3)0.026 (3)0.000 (2)0.002 (2)0.002 (2)
C260.025 (3)0.020 (3)0.020 (2)0.002 (2)0.001 (2)0.006 (2)
C270.023 (3)0.022 (3)0.015 (2)0.001 (2)0.001 (2)0.004 (2)
O280.030 (2)0.024 (2)0.0236 (19)0.0094 (16)0.0106 (16)0.0057 (15)
C290.038 (3)0.022 (3)0.023 (3)0.003 (2)0.012 (2)0.003 (2)
C300.060 (5)0.032 (3)0.033 (3)0.008 (3)0.021 (3)0.006 (3)
O310.032 (2)0.0198 (19)0.0261 (19)0.0098 (16)0.0003 (17)0.0024 (16)
C320.047 (4)0.017 (3)0.028 (3)0.010 (2)0.010 (3)0.002 (2)
Br330.0888 (10)0.0888 (10)0.374 (5)0.0231 (12)0.1006 (19)0.1006 (19)
C360.066 (4)0.059 (4)0.086 (5)0.011 (4)0.008 (4)0.039 (4)
C350.072 (5)0.060 (4)0.117 (5)0.012 (4)0.041 (4)0.025 (4)
C340.055 (3)0.055 (3)0.165 (6)0.003 (4)0.044 (4)0.044 (4)
C370.061 (4)0.061 (4)0.088 (6)0.006 (5)0.027 (4)0.027 (4)
Geometric parameters (Å, º) top
S1—O21.440 (4)C21—H2120.951
S1—O31.446 (4)C21—H2110.966
S1—C41.759 (6)C21—H2130.946
S1—C51.767 (5)C22—C231.387 (7)
C4—H410.954C22—C271.383 (7)
C4—H430.949C23—C241.389 (7)
C4—H420.963C23—H2310.922
C5—C61.533 (7)C24—C251.412 (7)
C5—H520.951C24—O281.374 (6)
C5—H510.951C25—C261.379 (8)
C6—N71.472 (7)C25—O311.361 (7)
C6—C221.533 (7)C26—C271.389 (8)
C6—H610.966C26—H2610.928
N7—C81.398 (7)C27—H2710.919
N7—C111.403 (7)O28—C291.443 (7)
C8—C91.473 (7)C29—C301.514 (8)
C8—O121.225 (7)C29—H2910.971
C9—C101.388 (7)C29—H2920.981
C9—C141.403 (8)C30—H3010.946
C10—C111.475 (7)C30—H3020.961
C10—C171.383 (8)C30—H3030.940
C11—O131.219 (7)O31—C321.426 (7)
C14—C151.394 (8)C32—H3210.958
C14—N181.405 (7)C32—H3220.962
C15—C161.412 (8)C32—H3230.955
C15—H1510.922Br33—C341.867 (13)
C16—C171.393 (8)C36—C351.468 (13)
C16—H1610.932C36—C371.374 (13)
C17—H1710.918C36—H3610.931
N18—C191.362 (7)C35—C341.409 (9)
N18—H1810.852C35—H3510.951
C19—O201.215 (7)C37—H3710.924
C19—C211.520 (8)
O2—S1—O3117.8 (2)C19—C21—H212108.8
O2—S1—C4108.9 (3)C19—C21—H211108.8
O3—S1—C4108.5 (3)H212—C21—H211110.1
O2—S1—C5109.0 (2)C19—C21—H213108.6
O3—S1—C5109.3 (2)H212—C21—H213111.3
C4—S1—C5102.2 (3)H211—C21—H213109.3
S1—C4—H41111.5C6—C22—C23121.9 (5)
S1—C4—H43109.5C6—C22—C27118.6 (5)
H41—C4—H43111.0C23—C22—C27119.5 (5)
S1—C4—H42109.1C22—C23—C24120.6 (5)
H41—C4—H42108.3C22—C23—H231119.2
H43—C4—H42107.4C24—C23—H231120.1
S1—C5—C6113.4 (3)C23—C24—C25119.6 (5)
S1—C5—H52107.1C23—C24—O28124.2 (5)
C6—C5—H52109.0C25—C24—O28116.2 (5)
S1—C5—H51109.2C24—C25—C26119.1 (5)
C6—C5—H51108.6C24—C25—O31115.9 (5)
H52—C5—H51109.4C26—C25—O31125.0 (5)
C5—C6—N7111.8 (4)C25—C26—C27120.8 (5)
C5—C6—C22111.7 (4)C25—C26—H261118.6
N7—C6—C22112.2 (4)C27—C26—H261120.6
C5—C6—H61108.6C26—C27—C22120.4 (5)
N7—C6—H61105.2C26—C27—H271119.3
C22—C6—H61107.0C22—C27—H271120.3
C6—N7—C8123.9 (4)C24—O28—C29116.7 (4)
C6—N7—C11125.1 (4)O28—C29—C30107.9 (5)
C8—N7—C11110.7 (4)O28—C29—H291110.7
N7—C8—C9106.3 (4)C30—C29—H291107.6
N7—C8—O12124.7 (5)O28—C29—H292109.4
C9—C8—O12129.0 (5)C30—C29—H292109.2
C8—C9—C10108.7 (4)H291—C29—H292111.9
C8—C9—C14129.7 (5)C29—C30—H301108.9
C10—C9—C14121.7 (5)C29—C30—H302110.1
C9—C10—C11107.5 (5)H301—C30—H302110.6
C9—C10—C17122.2 (5)C29—C30—H303109.9
C11—C10—C17130.2 (5)H301—C30—H303107.5
C10—C11—N7106.8 (4)H302—C30—H303109.9
C10—C11—O13129.2 (5)C25—O31—C32116.0 (4)
N7—C11—O13124.1 (5)O31—C32—H321110.6
C9—C14—C15117.0 (5)O31—C32—H322109.2
C9—C14—N18117.7 (5)H321—C32—H322108.3
C15—C14—N18125.2 (5)O31—C32—H323110.5
C14—C15—C16120.2 (5)H321—C32—H323109.3
C14—C15—H151119.6H322—C32—H323108.8
C16—C15—H151120.2C35—C36—C37117.3 (7)
C15—C16—C17122.5 (5)C35—C36—H361121.8
C15—C16—H161118.9C37—C36—H361120.9
C17—C16—H161118.6C36—C35—C34119.7 (8)
C16—C17—C10116.3 (5)C36—C35—H351117.0
C16—C17—H171122.6C34—C35—H351123.3
C10—C17—H171121.1Br33—C34—C35119.8 (6)
C14—N18—C19127.9 (5)Br33—C34—C35i119.8 (6)
C14—N18—H181115.0C35—C34—C35i120.3 (11)
C19—N18—H181116.8C36i—C37—C36125.3 (12)
N18—C19—O20123.9 (5)C36i—C37—H371117.3
N18—C19—C21113.1 (5)C36—C37—H371117.3
O20—C19—C21123.0 (5)
Symmetry code: (i) y, x, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H43···O3ii0.952.493.367 (8)154
C5—H52···O20iii0.952.513.448 (8)168
C5—H51···O130.952.493.095 (8)121
C5—H51···O13ii0.952.323.149 (8)146
C15—H151···O200.922.302.889 (8)121
C23—H231···O13ii0.922.463.377 (8)177
C26—H261···O2iii0.932.453.351 (8)164
C27—H271···O3iii0.922.523.256 (8)137
C32—H321···O20iv0.962.593.502 (8)160
C4—H42···O12v0.962.353.034 (8)127
N18—H181···O120.852.292.965 (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, x1/2, z+1/4.
(Apremilast_chlorbenzen) top
Crystal data top
C33.33H35.33Cl0.67N2.67O9.33S1.33Dx = 1.411 Mg m3
Mr = 689.05Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 29828 reflections
a = 12.8788 (1) Åθ = 3–68°
c = 29.3261 (1) ŵ = 2.11 mm1
V = 4864.13 (8) Å3T = 120 K
Z = 6Block, colorless
F(000) = 21680.36 × 0.22 × 0.17 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4293 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.035
ω scansθmax = 67.6°, θmin = 4.6°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.27, Tmax = 0.70k = 1315
45672 measured reflectionsl = 3533
4375 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.032 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.06P)2 + 2.22P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.090(Δ/σ)max = 0.001
S = 0.99Δρmax = 0.74 e Å3
4375 reflectionsΔρmin = 0.48 e Å3
353 parametersAbsolute structure: Flack (1983), 1792 Friedel-pairs
120 restraintsAbsolute structure parameter: 0.002 (15)
Primary atom site location: Other
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.83338 (4)0.59281 (4)0.535290 (15)0.0209
O20.78621 (12)0.68571 (11)0.55365 (5)0.0285
O30.92110 (11)0.55006 (12)0.55933 (5)0.0297
C40.86911 (19)0.61702 (18)0.47858 (7)0.0337
C50.73663 (15)0.49608 (15)0.52942 (6)0.0198
C60.70029 (14)0.45069 (15)0.57500 (6)0.0192
N70.65371 (12)0.53190 (12)0.60392 (5)0.0181
C80.69400 (14)0.56082 (14)0.64653 (6)0.0178
C90.63211 (14)0.65106 (14)0.66189 (6)0.0186
C100.55915 (14)0.67363 (15)0.62873 (6)0.0194
C110.57215 (14)0.59752 (14)0.59125 (6)0.0188
O120.76558 (10)0.51740 (11)0.66566 (4)0.0228
O130.52369 (11)0.58965 (11)0.55585 (4)0.0242
C140.63792 (14)0.70680 (14)0.70243 (6)0.0188
C150.56687 (15)0.78869 (15)0.70766 (7)0.0228
C160.49488 (15)0.81118 (16)0.67379 (7)0.0260
C170.48837 (16)0.75369 (15)0.63339 (7)0.0242
N180.71178 (12)0.67619 (12)0.73485 (5)0.0202
C190.73064 (15)0.71863 (15)0.77692 (6)0.0224
C200.80639 (17)0.65822 (17)0.80517 (7)0.0282
O210.68941 (12)0.79803 (11)0.79057 (5)0.0274
C220.62850 (14)0.35783 (15)0.56808 (6)0.0195
C230.57242 (14)0.34285 (15)0.52768 (6)0.0210
C240.50920 (15)0.25649 (15)0.52240 (6)0.0215
C250.50205 (15)0.18262 (15)0.55782 (7)0.0221
C260.55710 (16)0.19813 (15)0.59768 (7)0.0232
C270.62053 (16)0.28568 (15)0.60251 (6)0.0222
O280.45004 (12)0.23601 (10)0.48454 (5)0.0271
C290.44727 (18)0.31466 (15)0.44969 (7)0.0271
C300.3625 (2)0.28688 (19)0.41678 (8)0.0422
O310.43929 (12)0.09896 (11)0.54950 (5)0.0282
C320.42404 (19)0.02912 (17)0.58662 (7)0.0340
Cl400.3979 (2)0.4897 (2)0.67626 (9)0.11470.5000
C410.4632 (4)0.4996 (5)0.72509 (16)0.06170.5000
H410.92380.67170.48090.0513*
C420.4285 (7)0.5696 (9)0.7571 (3)0.06630.5000
H420.89780.55480.46420.0511*
C430.4824 (5)0.5842 (4)0.7959 (2)0.06480.5000
H430.80760.64340.46160.0510*
C440.5634 (4)0.5149 (4)0.80783 (16)0.05510.5000
C450.5933 (5)0.4392 (6)0.7779 (2)0.05610.5000
C460.5427 (7)0.4306 (6)0.7359 (2)0.06510.5000
H510.76860.44140.51130.0239*
H520.68340.52940.51190.0233*
H610.76130.42730.59290.0229*
H1510.56650.82750.73400.0263*
H1610.44890.86690.67810.0298*
H1710.43870.76970.61050.0292*
H1810.75420.61880.72660.0244*
H2010.83100.70220.82970.0428*
H2020.76970.59880.81630.0434*
H2030.86540.63940.78720.0428*
H2310.57850.39230.50380.0253*
H2610.55250.15030.62110.0271*
H2710.66020.29640.62950.0271*
H2910.42980.38230.46380.0330*
H2920.51580.31960.43420.0329*
H3010.35240.34110.39520.0622*
H3020.29670.27410.43240.0631*
H3030.38090.22640.39840.0625*
H3210.37780.02310.57670.0493*
H3220.39320.06380.61170.0496*
H3230.48910.00160.59550.0506*
H4210.37790.61960.74860.0766*0.5000
H4310.46080.63580.81780.0804*0.5000
H4410.59750.52050.83700.0684*0.5000
H4510.64830.39310.78550.0661*0.5000
H4610.56270.37850.71470.0759*0.5000
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0216 (2)0.0217 (2)0.0196 (2)0.00418 (18)0.00156 (18)0.00186 (18)
O20.0348 (8)0.0228 (7)0.0281 (7)0.0012 (6)0.0017 (6)0.0050 (6)
O30.0239 (7)0.0321 (8)0.0333 (8)0.0032 (6)0.0042 (6)0.0012 (6)
C40.0364 (12)0.0375 (12)0.0273 (10)0.0063 (9)0.0109 (9)0.0021 (9)
C50.0204 (9)0.0217 (9)0.0171 (8)0.0027 (7)0.0003 (7)0.0031 (7)
C60.0194 (9)0.0204 (9)0.0179 (9)0.0020 (7)0.0007 (7)0.0001 (7)
N70.0184 (7)0.0210 (8)0.0148 (7)0.0005 (6)0.0016 (6)0.0012 (6)
C80.0191 (9)0.0192 (9)0.0151 (8)0.0030 (7)0.0002 (7)0.0031 (7)
C90.0185 (9)0.0180 (9)0.0193 (9)0.0030 (7)0.0003 (7)0.0034 (7)
C100.0190 (9)0.0199 (9)0.0194 (8)0.0020 (7)0.0008 (7)0.0034 (7)
C110.0188 (9)0.0193 (9)0.0183 (9)0.0021 (7)0.0003 (7)0.0029 (7)
O120.0232 (7)0.0242 (7)0.0209 (6)0.0047 (5)0.0044 (5)0.0009 (5)
O130.0226 (7)0.0300 (7)0.0201 (6)0.0001 (6)0.0048 (5)0.0013 (6)
C140.0187 (9)0.0171 (9)0.0204 (9)0.0027 (7)0.0003 (7)0.0026 (7)
C150.0234 (10)0.0218 (9)0.0233 (9)0.0007 (8)0.0014 (7)0.0025 (8)
C160.0224 (10)0.0227 (10)0.0329 (11)0.0055 (8)0.0021 (8)0.0015 (8)
C170.0218 (10)0.0241 (10)0.0268 (10)0.0030 (8)0.0050 (8)0.0020 (8)
N180.0229 (8)0.0193 (8)0.0185 (7)0.0025 (6)0.0025 (6)0.0008 (6)
C190.0228 (10)0.0244 (10)0.0201 (9)0.0032 (8)0.0005 (7)0.0010 (8)
C200.0316 (11)0.0312 (11)0.0218 (9)0.0011 (9)0.0065 (8)0.0012 (8)
O210.0328 (8)0.0270 (7)0.0224 (7)0.0040 (6)0.0012 (6)0.0047 (6)
C220.0191 (9)0.0197 (9)0.0198 (9)0.0032 (7)0.0013 (7)0.0003 (7)
C230.0215 (9)0.0207 (9)0.0206 (9)0.0010 (7)0.0015 (7)0.0040 (7)
C240.0227 (9)0.0201 (9)0.0216 (9)0.0020 (7)0.0027 (7)0.0000 (7)
C250.0221 (10)0.0179 (9)0.0262 (10)0.0004 (7)0.0021 (8)0.0017 (8)
C260.0269 (10)0.0215 (10)0.0213 (9)0.0032 (8)0.0027 (8)0.0045 (7)
C270.0253 (10)0.0241 (10)0.0174 (9)0.0014 (8)0.0019 (7)0.0001 (7)
O280.0307 (8)0.0225 (7)0.0280 (7)0.0051 (6)0.0103 (6)0.0045 (6)
C290.0359 (11)0.0214 (10)0.0241 (9)0.0007 (8)0.0101 (8)0.0026 (8)
C300.0600 (16)0.0285 (12)0.0381 (13)0.0051 (11)0.0250 (12)0.0030 (10)
O310.0345 (8)0.0202 (7)0.0298 (7)0.0071 (6)0.0012 (6)0.0033 (6)
C320.0520 (14)0.0217 (10)0.0282 (11)0.0088 (10)0.0117 (10)0.0006 (8)
Cl400.1142 (19)0.142 (2)0.0877 (15)0.0859 (18)0.0338 (14)0.0533 (15)
C410.052 (3)0.065 (3)0.069 (4)0.033 (3)0.004 (3)0.026 (3)
C420.050 (4)0.060 (4)0.088 (6)0.007 (2)0.037 (4)0.043 (4)
C430.071 (4)0.050 (3)0.073 (4)0.018 (3)0.018 (3)0.004 (3)
C440.050 (3)0.044 (3)0.070 (4)0.022 (2)0.013 (3)0.012 (3)
C450.038 (3)0.045 (3)0.085 (4)0.013 (2)0.015 (3)0.036 (3)
C460.059 (4)0.057 (5)0.079 (6)0.027 (4)0.023 (4)0.017 (4)
Geometric parameters (Å, º) top
S1—O21.4459 (15)C25—C261.382 (3)
S1—O31.4411 (15)C25—O311.369 (2)
S1—C41.754 (2)C26—C271.400 (3)
S1—C51.7703 (19)C26—H2610.923
C4—H410.998C27—H2710.952
C4—H420.979O28—C291.440 (2)
C4—H430.995C29—C301.500 (3)
C5—C61.532 (2)C29—H2910.990
C5—H510.973C29—H2920.995
C5—H520.958C30—H3010.952
C6—N71.474 (2)C30—H3020.977
C6—C221.525 (3)C30—H3030.975
C6—H610.993O31—C321.426 (2)
N7—C81.403 (2)C32—H3210.944
N7—C111.399 (2)C32—H3220.948
C8—C91.479 (3)C32—H3230.963
C8—O121.215 (2)Cl40—H441i1.587
C9—C101.383 (3)Cl40—C44i1.395 (6)
C9—C141.391 (3)Cl40—H431i0.791
C10—C111.482 (3)Cl40—C411.666 (5)
C10—C171.383 (3)C41—C41i1.611 (9)
C11—O131.216 (2)C41—C45i1.738 (7)
C14—C151.405 (3)C41—C44i1.292 (8)
C14—N181.401 (2)C41—C42i1.144 (8)
C15—C161.389 (3)C41—C43i0.897 (6)
C15—H1510.921C41—C421.376 (7)
C16—C171.400 (3)C41—C461.393 (6)
C16—H1610.939C42—H421i0.932
C17—H1710.950C42—C43i1.701 (13)
N18—C191.371 (2)C42—C431.347 (7)
N18—H1810.950C42—H4210.950
C19—C201.498 (3)C43—C441.416 (6)
C19—O211.220 (2)C43—H4310.965
C20—H2010.969C44—C46i1.483 (10)
C20—H2020.957C44—C451.367 (6)
C20—H2030.956C44—H4410.965
C22—C231.401 (3)C45—C45i1.741 (14)
C22—C271.376 (3)C45—C461.3992 (10)
C23—C241.387 (3)C45—H4510.950
C23—H2310.950C46—C46i0.961 (13)
C24—C251.411 (3)C46—H4610.950
C24—O281.372 (2)H451—H461i0.665
O2—S1—O3117.60 (9)H322—C32—H323110.3
O2—S1—C4108.44 (10)H441i—Cl40—C44i37.0
O3—S1—C4109.04 (10)H441i—Cl40—H431i171.2
O2—S1—C5108.84 (9)C44i—Cl40—H431i139.7
O3—S1—C5109.30 (9)H441i—Cl40—C4186.0
C4—S1—C5102.57 (10)C44i—Cl40—C4149.0 (3)
S1—C4—H41104.2H431i—Cl40—C4191.4
S1—C4—H42111.3C41i—C41—Cl40162.4 (3)
H41—C4—H42109.9C41i—C41—C45i92.0 (3)
S1—C4—H43109.0Cl40—C41—C45i105.6 (4)
H41—C4—H43110.8C41i—C41—C44i143.1 (4)
H42—C4—H43111.3Cl40—C41—C44i54.5 (3)
S1—C5—C6113.49 (13)C45i—C41—C44i51.1 (3)
S1—C5—H51105.3C41i—C41—C42i57.0 (5)
C6—C5—H51109.2Cl40—C41—C42i105.6 (5)
S1—C5—H52103.9C45i—C41—C42i148.0 (7)
C6—C5—H52114.9C44i—C41—C42i158.4 (7)
H51—C5—H52109.5C41i—C41—C43i138.5 (7)
C5—C6—N7110.83 (15)Cl40—C41—C43i24.0 (5)
C5—C6—C22111.60 (15)C45i—C41—C43i129.4 (8)
N7—C6—C22112.72 (15)C44i—C41—C43i78.3 (6)
C5—C6—H61109.7C42i—C41—C43i81.6 (6)
N7—C6—H61103.5C41i—C41—C4244.2 (2)
C22—C6—H61108.2Cl40—C41—C42118.2 (4)
C6—N7—C8123.38 (15)C45i—C41—C42136.1 (4)
C6—N7—C11125.56 (14)C44i—C41—C42172.7 (5)
C8—N7—C11110.73 (15)C42i—C41—C4215.9 (8)
N7—C8—C9106.28 (15)C41i—C41—C4676.4 (2)
N7—C8—O12124.69 (17)Cl40—C41—C46121.2 (4)
C9—C8—O12129.02 (17)C45i—C41—C4616.2 (4)
C8—C9—C10108.49 (16)C44i—C41—C4666.9 (5)
C8—C9—C14129.54 (17)C42i—C41—C46133.2 (6)
C10—C9—C14121.94 (18)C43i—C41—C4294.5 (8)
C9—C10—C11107.80 (16)C43i—C41—C46145.1 (8)
C9—C10—C17122.35 (18)C42—C41—C46120.14 (18)
C11—C10—C17129.84 (17)H421i—C42—C43i93.4
C10—C11—N7106.70 (14)H421i—C42—C41124.7
C10—C11—O13129.09 (17)C43i—C42—C4131.7 (3)
N7—C11—O13124.21 (17)H421i—C42—C41i152.5
C9—C14—C15116.47 (17)C43i—C42—C41i110.5 (4)
C9—C14—N18118.11 (16)C41—C42—C41i78.9 (4)
C15—C14—N18125.40 (17)H421i—C42—C43113.1
C14—C15—C16120.88 (18)C43i—C42—C43151.3 (4)
C14—C15—H151120.1C41—C42—C43120.03 (18)
C16—C15—H151119.0C41i—C42—C4341.2 (4)
C15—C16—C17122.34 (18)H421i—C42—H4215.8
C15—C16—H161118.9C43i—C42—H42187.7
C17—C16—H161118.8C41—C42—H421119.1
C16—C17—C10116.01 (18)C41i—C42—H421157.8
C16—C17—H171121.6C43—C42—H421118.8
C10—C17—H171122.4C42i—C43—C428.4 (10)
C14—N18—C19128.21 (17)C42i—C43—C41i53.7 (6)
C14—N18—H181115.9C42—C43—C41i57.2 (5)
C19—N18—H181115.9C42i—C43—C44117.1 (2)
N18—C19—C20113.96 (17)C42—C43—C44120.04 (18)
N18—C19—O21123.53 (18)C41i—C43—C4463.4 (5)
C20—C19—O21122.51 (18)C42i—C43—H431124.0
C19—C20—H201108.7C42—C43—H431120.6
C19—C20—H202106.4C41i—C43—H431177.7
H201—C20—H202112.1C44—C43—H431118.9
C19—C20—H203110.2C46i—C44—C4398.1 (2)
H201—C20—H203107.3C46i—C44—C41i59.8 (4)
H202—C20—H203112.2C43—C44—C41i38.4 (3)
C6—C22—C23122.22 (17)C46i—C44—Cl40i135.8 (4)
C6—C22—C27118.49 (17)C43—C44—Cl40i38.2 (3)
C23—C22—C27119.28 (18)C41i—C44—Cl40i76.5 (4)
C22—C23—C24120.50 (17)C46i—C44—C4522.1 (2)
C22—C23—H231119.2C43—C44—C45119.90 (17)
C24—C23—H231120.3C41i—C44—C4581.6 (3)
C23—C24—C25119.77 (17)Cl40i—C44—C45157.9 (3)
C23—C24—O28124.78 (17)C46i—C44—H441141.3
C25—C24—O28115.44 (17)C43—C44—H441120.5
C24—C25—C26119.45 (17)C41i—C44—H441158.8
C24—C25—O31115.97 (16)Cl40i—C44—H44182.3
C26—C25—O31124.58 (17)C45—C44—H441119.6
C25—C26—C27120.11 (17)C44—C45—C41i47.4 (3)
C25—C26—H261119.9C44—C45—C45i135.0 (2)
C27—C26—H261120.0C41i—C45—C45i87.7 (3)
C26—C27—C22120.88 (18)C44—C45—C46119.42 (17)
C26—C27—H271121.0C41i—C45—C4672.1 (3)
C22—C27—H271118.1C45i—C45—C4616.3 (3)
C24—O28—C29116.94 (15)C44—C45—H451120.4
O28—C29—C30107.88 (18)C41i—C45—H451167.7
O28—C29—H291109.1C45i—C45—H451104.4
C30—C29—H291108.3C46—C45—H451120.2
O28—C29—H292110.3C44i—C46—C45172.1 (5)
C30—C29—H292111.5C44i—C46—C4153.3 (4)
H291—C29—H292109.6C45—C46—C41119.47 (17)
C29—C30—H301110.7C44i—C46—C46i154.9 (6)
C29—C30—H302111.7C45—C46—C46i17.2 (5)
H301—C30—H302108.4C41—C46—C46i103.3 (3)
C29—C30—H303111.7C44i—C46—H46166.9
H301—C30—H303104.6C45—C46—H461120.4
H302—C30—H303109.5C41—C46—H461120.1
C25—O31—C32116.22 (16)C46i—C46—H461136.0
O31—C32—H321107.5C42—H421—C42i25.6
O31—C32—H322110.7C43—H431—Cl40i62.3
H321—C32—H322108.1C44—H441—Cl40i60.6
O31—C32—H323110.3H461i—H451—C4522.7
H321—C32—H323109.8H451i—H461—C46127.1
Symmetry code: (i) y+1, x+1, z+3/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H41···O12ii1.002.403.056 (4)122
C4—H43···O2iii1.002.463.350 (4)149
C5—H51···O21iv0.972.453.410 (4)167
C5—H52···O13iii0.962.333.156 (4)145
C15—H151···O210.922.322.901 (4)121
N18—H181···O120.952.222.963 (4)134
C23—H231···O13iii0.952.443.387 (4)178
C26—H261···O3iv0.922.443.339 (4)165
C27—H271···O2iv0.952.523.267 (4)135
C45—H451···O2v0.952.603.543 (4)173
Symmetry codes: (ii) y+1/2, x+3/2, z1/4; (iii) y, x, z+1; (iv) x+3/2, y1/2, z+5/4; (v) y+3/2, x1/2, z+1/4.
(ApreHexa) top
Crystal data top
2(C22H24N2O7S)·(C6F6)Dx = 1.514 Mg m3
Mr = 1107.1Cu Kα radiation, λ = 1.54184 Å
Tetragonal, P41212Cell parameters from 32712 reflections
Hall symbol: P 43n;2nwθ = 3.0–74.0°
a = 12.8425 (1) ŵ = 1.84 mm1
c = 29.4534 (2) ÅT = 120 K
V = 4857.74 (6) Å3Block, yellow
Z = 40.34 × 0.25 × 0.17 mm
F(000) = 2296
Data collection top
SuperNova, Dual, Cu at home/near, AtlasS2
diffractometer
4928 independent reflections
Radiation source: X-ray tube4897 reflections with I > 3σ(I)
Mirror monochromatorRint = 0.018
Detector resolution: 5.2027 pixels mm-1θmax = 74.3°, θmin = 3.8°
ω scansh = 1515
Absorption correction: analytical
CrysAlisPro 1.171.40.67a (Rigaku Oxford Diffraction, 2019) Analytical numeric absorption correction based on crystal shape
k = 1515
Tmin = 0.671, Tmax = 0.796l = 3636
41296 measured reflections
Refinement top
Refinement on F2H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.023Weighting scheme based on measured s.u.'s w = 1/(σ2(I) + 0.0016I2)
wR(F2) = 0.072(Δ/σ)max = 0.021
S = 1.66Δρmax = 0.16 e Å3
4928 reflectionsΔρmin = 0.21 e Å3
349 parametersAbsolute structure: 2035 of Friedel pairs used in the refinement
1 restraintAbsolute structure parameter: 0.004 (9)
93 constraints
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.16716 (2)0.59424 (2)0.712495 (8)0.01827 (7)
F10.79300 (9)0.20700 (9)0.750.0599 (4)
F20.91597 (10)0.18083 (8)0.82396 (3)0.0541 (3)
F31.06368 (9)0.03077 (9)0.82434 (4)0.0554 (3)
F41.09175 (9)0.09175 (9)0.750.0610 (4)
O10.47431 (6)0.59043 (7)0.69488 (3)0.0212 (2)
O20.23649 (7)0.51093 (6)0.58451 (3)0.0202 (2)
O30.21769 (7)0.68444 (7)0.69299 (3)0.0252 (2)
O40.07948 (7)0.55094 (7)0.68841 (3)0.0269 (2)
O50.54631 (7)0.23422 (6)0.76843 (3)0.0202 (2)
O60.55846 (7)0.09487 (7)0.70395 (3)0.0223 (2)
O70.31494 (7)0.78740 (7)0.45864 (3)0.0275 (2)
N10.34699 (7)0.52852 (7)0.64649 (3)0.0155 (2)
N20.28903 (7)0.66880 (7)0.51529 (3)0.0185 (2)
C10.42738 (8)0.59541 (9)0.65931 (3)0.0162 (3)
C20.30732 (8)0.55534 (8)0.60383 (3)0.0158 (3)
C30.36833 (8)0.64609 (8)0.58815 (4)0.0159 (3)
C40.36203 (8)0.70139 (8)0.54747 (4)0.0164 (3)
C50.43298 (9)0.78404 (9)0.54194 (4)0.0200 (3)
C60.50511 (9)0.80799 (9)0.57592 (4)0.0223 (3)
C70.51127 (9)0.75145 (9)0.61652 (4)0.0213 (3)
C80.44134 (8)0.67054 (9)0.62133 (3)0.0172 (3)
C90.29946 (8)0.44849 (8)0.67568 (3)0.0161 (3)
C100.26178 (8)0.49535 (8)0.72064 (3)0.0173 (3)
C110.12892 (11)0.62580 (11)0.76816 (4)0.0293 (3)
C120.37136 (8)0.35585 (9)0.68342 (4)0.0169 (3)
C130.42630 (8)0.34120 (8)0.72406 (3)0.0177 (3)
C140.48941 (8)0.25425 (8)0.73014 (4)0.0171 (3)
C150.49734 (9)0.17951 (8)0.69495 (4)0.0176 (3)
C160.44369 (9)0.19507 (9)0.65468 (4)0.0195 (3)
C170.38102 (9)0.28280 (9)0.64905 (4)0.0189 (3)
C180.54743 (9)0.31501 (9)0.80237 (4)0.0210 (3)
C190.62629 (11)0.28555 (11)0.83813 (4)0.0305 (4)
C200.57506 (10)0.02516 (9)0.66685 (4)0.0246 (3)
C210.27073 (9)0.71040 (9)0.47284 (3)0.0195 (3)
C220.19379 (9)0.64936 (10)0.44499 (4)0.0241 (3)
C230.86636 (12)0.13364 (12)0.750.0356 (4)
C240.92905 (13)0.12041 (11)0.78747 (5)0.0365 (4)
C251.00426 (12)0.04442 (12)0.78760 (5)0.0369 (4)
C261.01845 (12)0.01845 (12)0.750.0376 (5)
H1c50.43180.8244060.5145120.024*
H1c60.5520590.8651730.5712810.0268*
H1c70.5612430.7680110.6396590.0256*
H1c90.2396890.4222570.6597990.0193*
H1c100.3201030.5234180.7369510.0208*
H2c100.2331660.4412840.7393740.0208*
H1c110.0997350.5653690.7825180.0352*
H2c110.1884370.6490240.7850860.0352*
H3c110.0777270.6802290.7672650.0352*
H1c130.4203220.3917110.747940.0212*
H1c160.4497060.1452030.6305430.0235*
H1c170.3441250.2926950.6210350.0226*
H1c180.4797540.3203970.8160090.0252*
H2c180.5673390.3797620.7885910.0252*
H1c190.6301440.3396630.8605560.0366*
H2c190.6055670.2215770.8523690.0366*
H3c190.6933010.2766750.824220.0366*
H1c200.616770.0325250.6768020.0295*
H2c200.5091860.0000050.6560330.0295*
H3c200.6103710.0611510.642790.0295*
H1c220.1386270.6249010.4642290.0289*
H2c220.1653660.6932630.4217020.0289*
H3c220.228280.5909840.4312730.0289*
H1n20.2529 (11)0.6157 (8)0.5235 (5)0.0223*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.01925 (13)0.02004 (13)0.01552 (12)0.00511 (9)0.00156 (9)0.00123 (9)
F10.0539 (6)0.0539 (6)0.0718 (10)0.0121 (7)0.0118 (6)0.0118 (6)
F20.0792 (7)0.0442 (5)0.0390 (5)0.0212 (5)0.0123 (5)0.0116 (4)
F30.0563 (6)0.0652 (7)0.0447 (5)0.0225 (5)0.0178 (5)0.0206 (5)
F40.0488 (5)0.0488 (5)0.0855 (11)0.0076 (7)0.0127 (6)0.0127 (6)
O10.0200 (4)0.0278 (4)0.0159 (3)0.0019 (3)0.0047 (3)0.0024 (3)
O20.0231 (4)0.0210 (4)0.0164 (3)0.0044 (3)0.0048 (3)0.0003 (3)
O30.0301 (4)0.0211 (4)0.0243 (4)0.0045 (3)0.0044 (3)0.0048 (3)
O40.0225 (4)0.0312 (4)0.0269 (4)0.0044 (3)0.0049 (3)0.0010 (3)
O50.0245 (4)0.0185 (4)0.0177 (3)0.0049 (3)0.0067 (3)0.0034 (3)
O60.0277 (4)0.0186 (4)0.0205 (3)0.0072 (3)0.0016 (3)0.0031 (3)
O70.0311 (4)0.0311 (5)0.0202 (4)0.0089 (4)0.0026 (3)0.0061 (3)
N10.0162 (4)0.0181 (4)0.0121 (4)0.0006 (3)0.0018 (3)0.0008 (3)
N20.0210 (5)0.0186 (4)0.0160 (4)0.0029 (3)0.0031 (3)0.0007 (3)
C10.0144 (4)0.0190 (5)0.0153 (4)0.0024 (4)0.0001 (4)0.0040 (4)
C20.0177 (5)0.0169 (5)0.0129 (4)0.0034 (4)0.0008 (4)0.0010 (3)
C30.0159 (5)0.0160 (5)0.0156 (5)0.0018 (4)0.0011 (3)0.0024 (4)
C40.0167 (5)0.0171 (5)0.0154 (5)0.0013 (4)0.0003 (4)0.0017 (4)
C50.0185 (5)0.0201 (5)0.0213 (5)0.0004 (4)0.0012 (4)0.0019 (4)
C60.0204 (5)0.0201 (5)0.0264 (5)0.0031 (4)0.0015 (4)0.0006 (4)
C70.0184 (5)0.0229 (5)0.0227 (5)0.0006 (4)0.0029 (4)0.0024 (4)
C80.0170 (5)0.0183 (5)0.0163 (4)0.0029 (4)0.0005 (4)0.0029 (4)
C90.0175 (5)0.0174 (5)0.0134 (4)0.0004 (4)0.0009 (3)0.0002 (4)
C100.0186 (5)0.0194 (5)0.0140 (4)0.0044 (4)0.0001 (4)0.0010 (4)
C110.0319 (6)0.0343 (7)0.0219 (5)0.0058 (5)0.0093 (5)0.0029 (5)
C120.0172 (5)0.0171 (5)0.0165 (5)0.0006 (4)0.0000 (4)0.0000 (4)
C130.0194 (5)0.0178 (5)0.0158 (5)0.0007 (4)0.0013 (4)0.0026 (4)
C140.0189 (5)0.0177 (5)0.0148 (4)0.0012 (4)0.0016 (4)0.0001 (4)
C150.0190 (5)0.0151 (4)0.0186 (5)0.0002 (4)0.0016 (4)0.0014 (4)
C160.0219 (5)0.0193 (5)0.0175 (5)0.0012 (4)0.0000 (4)0.0042 (4)
C170.0215 (5)0.0202 (5)0.0149 (4)0.0004 (4)0.0022 (4)0.0023 (4)
C180.0278 (6)0.0173 (5)0.0181 (4)0.0028 (4)0.0045 (4)0.0029 (4)
C190.0388 (7)0.0310 (6)0.0217 (5)0.0090 (5)0.0123 (5)0.0061 (5)
C200.0329 (6)0.0184 (5)0.0225 (5)0.0069 (5)0.0039 (4)0.0034 (4)
C210.0198 (5)0.0233 (5)0.0154 (4)0.0009 (4)0.0004 (4)0.0005 (4)
C220.0266 (6)0.0291 (6)0.0164 (5)0.0041 (5)0.0046 (4)0.0014 (4)
C230.0339 (6)0.0339 (6)0.0390 (10)0.0055 (8)0.0067 (5)0.0067 (5)
C240.0448 (8)0.0336 (7)0.0310 (6)0.0168 (6)0.0074 (6)0.0019 (5)
C250.0374 (7)0.0421 (7)0.0314 (6)0.0195 (6)0.0039 (6)0.0125 (6)
C260.0317 (6)0.0317 (6)0.0494 (11)0.0071 (8)0.0088 (6)0.0088 (6)
Geometric parameters (Å, º) top
S1—O31.4467 (9)C9—C121.5232 (15)
S1—O41.4423 (9)C9—H1c90.96
S1—C101.7740 (11)C10—H1c100.96
S1—C111.7589 (13)C10—H2c100.96
F1—C231.3323 (19)C11—H1c110.96
F2—C241.3362 (17)C11—H2c110.96
F3—C251.3356 (18)C11—H3c110.96
F4—C261.3314 (19)C12—C131.4021 (15)
O1—C11.2103 (13)C12—C171.3857 (15)
O2—C21.2151 (13)C13—C141.3914 (15)
O5—C141.3682 (13)C13—H1c130.96
O5—C181.4406 (13)C14—C151.4165 (15)
O6—C151.3668 (14)C15—C161.3861 (15)
O6—C201.4285 (14)C16—C171.3944 (16)
O7—C211.2146 (15)C16—H1c160.96
N1—C11.3952 (14)C17—H1c170.96
N1—C21.3987 (13)C18—C191.5095 (17)
N1—C91.4724 (13)C18—H1c180.96
N2—C41.3971 (14)C18—H2c180.96
N2—C211.3799 (14)C19—H1c190.96
N2—H1n20.859 (12)C19—H2c190.96
C1—C81.4881 (15)C19—H3c190.96
C2—C31.4783 (15)C20—H1c200.96
C3—C41.3953 (15)C20—H2c200.96
C3—C81.3901 (15)C20—H3c200.96
C4—C51.4083 (15)C21—C221.5045 (16)
C5—C61.3981 (16)C22—H1c220.96
C5—H1c50.96C22—H2c220.96
C6—C71.4011 (17)C22—H3c220.96
C6—H1c60.96C23—C241.3766 (18)
C7—C81.3807 (16)C23—C24i1.3766 (18)
C7—H1c70.96C24—C251.373 (2)
C9—C101.5330 (14)C25—C261.3826 (17)
O3—S1—O4117.62 (5)C9—C12—C17118.28 (9)
O3—S1—C10108.64 (5)C13—C12—C17119.19 (10)
O3—S1—C11108.11 (6)C12—C13—C14120.72 (9)
O4—S1—C10108.98 (5)C12—C13—H1c13119.64
O4—S1—C11109.22 (6)C14—C13—H1c13119.64
C10—S1—C11103.30 (6)O5—C14—C13124.62 (9)
C14—O5—C18116.22 (8)O5—C14—C15115.94 (9)
C15—O6—C20115.84 (9)C13—C14—C15119.43 (9)
C1—N1—C2111.16 (9)O6—C15—C14116.00 (9)
C1—N1—C9125.34 (8)O6—C15—C16124.48 (10)
C2—N1—C9123.05 (9)C14—C15—C16119.52 (10)
C4—N2—C21127.80 (9)C15—C16—C17120.34 (10)
C4—N2—H1n2114.2 (10)C15—C16—H1c16119.83
C21—N2—H1n2118.0 (10)C17—C16—H1c16119.83
O1—C1—N1124.76 (10)C12—C17—C16120.78 (10)
O1—C1—C8128.68 (10)C12—C17—H1c17119.61
N1—C1—C8106.55 (8)C16—C17—H1c17119.61
O2—C2—N1125.29 (10)O5—C18—C19108.08 (9)
O2—C2—C3128.35 (9)O5—C18—H1c18109.47
N1—C2—C3106.36 (9)O5—C18—H2c18109.47
C2—C3—C4129.70 (10)C19—C18—H1c18109.47
C2—C3—C8108.42 (9)C19—C18—H2c18109.47
C4—C3—C8121.86 (10)H1c18—C18—H2c18110.83
N2—C4—C3117.97 (9)C18—C19—H1c19109.47
N2—C4—C5125.56 (10)C18—C19—H2c19109.47
C3—C4—C5116.44 (10)C18—C19—H3c19109.47
C4—C5—C6120.78 (10)H1c19—C19—H2c19109.47
C4—C5—H1c5119.61H1c19—C19—H3c19109.47
C6—C5—H1c5119.61H2c19—C19—H3c19109.47
C5—C6—C7122.30 (11)O6—C20—H1c20109.47
C5—C6—H1c6118.85O6—C20—H2c20109.47
C7—C6—H1c6118.85O6—C20—H3c20109.47
C6—C7—C8116.15 (10)H1c20—C20—H2c20109.47
C6—C7—H1c7121.92H1c20—C20—H3c20109.47
C8—C7—H1c7121.92H2c20—C20—H3c20109.47
C1—C8—C3107.50 (9)O7—C21—N2123.19 (10)
C1—C8—C7130.04 (10)O7—C21—C22122.92 (10)
C3—C8—C7122.46 (10)N2—C21—C22113.85 (10)
N1—C9—C10111.18 (8)C21—C22—H1c22109.47
N1—C9—C12112.42 (8)C21—C22—H2c22109.47
N1—C9—H1c9106.97C21—C22—H3c22109.47
C10—C9—C12111.63 (8)H1c22—C22—H2c22109.47
C10—C9—H1c9107.83H1c22—C22—H3c22109.47
C12—C9—H1c9106.47H2c22—C22—H3c22109.47
S1—C10—C9112.36 (7)F1—C23—C24120.05 (9)
S1—C10—H1c10109.47F1—C23—C24i120.05 (9)
S1—C10—H2c10109.47C24—C23—C24i119.90 (14)
C9—C10—H1c10109.47F2—C24—C23119.98 (14)
C9—C10—H2c10109.47F2—C24—C25119.93 (13)
H1c10—C10—H2c10106.42C23—C24—C25120.08 (13)
S1—C11—H1c11109.47F3—C25—C24119.83 (13)
S1—C11—H2c11109.47F3—C25—C26119.80 (14)
S1—C11—H3c11109.47C24—C25—C26120.37 (13)
H1c11—C11—H2c11109.47F4—C26—C25120.41 (9)
H1c11—C11—H3c11109.47F4—C26—C25i120.41 (9)
H2c11—C11—H3c11109.47C25—C26—C25i119.19 (14)
C9—C12—C13122.53 (9)
Symmetry code: (i) y+1, x+1, z+3/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H1c5···O70.962.282.8842 (14)120
C10—H1c10···O10.962.493.0848 (13)120
C10—H1c10···O1i0.962.313.1537 (13)146
C11—H2c11···O3i0.962.453.3308 (16)152
C11—H3c11···O2ii0.962.403.0109 (15)121
C13—H1c13···O1i0.962.413.3707 (13)177
C16—H1c16···O4iii0.962.393.3216 (14)162
C17—H1c17···O3iii0.962.473.2484 (14)138
C20—H1c20···O7iv0.962.503.4531 (15)174
N2—H1n2···O20.859 (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, y1/2, z+5/4; (iv) y+3/2, x1/2, z+1/4.
(apremilastiodobenzene) top
Crystal data top
2(C22H24N2O7S)·C6H5IDx = 1.522 Mg m3
Mr = 1124.98Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 56749 reflections
a = 12.9104 (1) Åθ = 5–76°
c = 29.4495 (1) ŵ = 6.53 mm1
V = 4908.60 (8) Å3T = 95 K
Z = 4Block, colorless
F(000) = 23120.19 × 0.14 × 0.12 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
5108 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.030
ω scansθmax = 76.3°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1615
Tmin = 0.15, Tmax = 0.45k = 1516
86093 measured reflectionsl = 3737
5141 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.036 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.02P)2 + 11.85P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.079(Δ/σ)max = 0.004
S = 1.00Δρmax = 0.99 e Å3
5141 reflectionsΔρmin = 1.74 e Å3
329 parametersAbsolute structure: Flack (1983), 2129 Friedel-pairs
16 restraintsAbsolute structure parameter: 0.004 (4)
Primary atom site location: structure-invariant direct methods
Special details top

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 (Å2) top
xyzUiso*/Ueq
S10.39991 (5)0.84164 (5)0.28493 (2)0.0143
O20.44130 (15)0.92927 (16)0.30926 (7)0.0214
O30.30587 (16)0.79458 (16)0.30199 (7)0.0202
C40.3803 (2)0.8766 (2)0.22785 (9)0.0234
C50.4967 (2)0.7453 (2)0.28021 (8)0.0139
C60.5391 (2)0.7068 (2)0.32565 (8)0.0132
N70.45657 (17)0.66017 (17)0.35374 (7)0.0131
C80.4274 (2)0.6977 (2)0.39633 (8)0.0128
C90.3398 (2)0.63273 (19)0.41141 (8)0.0128
C100.3175 (2)0.5609 (2)0.37752 (8)0.0132
C110.39286 (19)0.5786 (2)0.34004 (9)0.0146
O120.46803 (15)0.77031 (15)0.41582 (6)0.0156
O130.40048 (16)0.53258 (14)0.30421 (6)0.0173
C140.2845 (2)0.6340 (2)0.45217 (9)0.0141
C150.2044 (2)0.5611 (2)0.45675 (9)0.0184
C160.1827 (2)0.4918 (2)0.42203 (10)0.0191
C170.2391 (2)0.4895 (2)0.38147 (9)0.0172
N180.31505 (18)0.70543 (17)0.48536 (7)0.0153
C190.2742 (2)0.7204 (2)0.52796 (9)0.0160
C200.3364 (2)0.7932 (2)0.55661 (9)0.0210
O210.19585 (16)0.67727 (16)0.54135 (6)0.0218
C220.6302 (2)0.6344 (2)0.31915 (9)0.0137
C230.6470 (2)0.5810 (2)0.27820 (9)0.0154
C240.7324 (2)0.5168 (2)0.27287 (9)0.0146
C250.8041 (2)0.5061 (2)0.30869 (9)0.0155
C260.7867 (2)0.5582 (2)0.34922 (9)0.0156
C270.7007 (2)0.6221 (2)0.35420 (9)0.0151
O280.75315 (15)0.46153 (15)0.23414 (6)0.0175
C290.6766 (2)0.4665 (2)0.19891 (9)0.0180
C300.7078 (2)0.3935 (3)0.16140 (10)0.0251
O310.88757 (15)0.44391 (15)0.30014 (6)0.0195
C320.9598 (2)0.4324 (2)0.33649 (10)0.0211
I330.582336 (19)0.582336 (19)0.50000.0824
C340.4679 (2)0.4679 (2)0.50000.0274
C350.4601 (3)0.4024 (3)0.46354 (11)0.0356
C360.3834 (3)0.3224 (3)0.46390 (13)0.0385
C370.3180 (3)0.3180 (3)0.500000 (7)0.0506
H510.55300.77610.26330.0181*
H520.46830.68720.26390.0182*
H610.56430.76700.34240.0171*
H1510.16540.55910.48330.0229*
H1610.12850.44490.42580.0231*
H1710.22500.44270.35830.0211*
H2010.29870.80860.58370.0312*
H2030.40100.76130.56500.0312*
H2020.35070.85670.54070.0310*
H2310.59980.58830.25430.0190*
H2610.83330.55040.37300.0192*
H2710.68980.65690.38150.0191*
H2910.67290.53720.18670.0221*
H2920.60910.44700.21050.0220*
H3020.65430.39180.13890.0392*
H3010.77140.41710.14790.0392*
H3030.71770.32500.17340.0389*
H3221.01450.38760.32650.0322*
H3210.98860.49870.34470.0320*
H3230.92570.40220.36230.0322*
H3510.50360.41130.43820.0421*
H3610.37940.27500.44070.0463*
H3710.26710.26710.50000.0603*
H430.32920.93010.22610.0379*
H1810.3667 (19)0.742 (2)0.4785 (7)0.018 (2)*
H420.35640.81780.21070.0378*
H410.44480.90130.21500.0379*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0136 (3)0.0153 (3)0.0139 (3)0.0036 (2)0.0021 (2)0.0016 (2)
O20.0225 (10)0.0171 (10)0.0247 (10)0.0039 (8)0.0029 (8)0.0032 (8)
O30.0168 (10)0.0234 (10)0.0204 (9)0.0020 (8)0.0043 (8)0.0026 (8)
C40.0223 (15)0.0288 (16)0.0192 (13)0.0061 (12)0.0008 (11)0.0090 (12)
C50.0147 (12)0.0144 (12)0.0126 (11)0.0049 (10)0.0023 (10)0.0000 (10)
C60.0155 (13)0.0146 (12)0.0095 (11)0.0011 (10)0.0000 (9)0.0000 (9)
N70.0158 (11)0.0135 (10)0.0102 (9)0.0009 (9)0.0014 (8)0.0029 (8)
C80.0128 (12)0.0141 (12)0.0115 (11)0.0039 (10)0.0009 (9)0.0016 (9)
C90.0144 (12)0.0111 (12)0.0128 (11)0.0021 (10)0.0028 (10)0.0012 (9)
C100.0148 (12)0.0124 (12)0.0123 (11)0.0035 (9)0.0030 (10)0.0004 (9)
C110.0153 (12)0.0122 (12)0.0163 (12)0.0033 (10)0.0018 (10)0.0016 (10)
O120.0183 (10)0.0150 (9)0.0133 (8)0.0016 (7)0.0023 (7)0.0037 (7)
O130.0232 (10)0.0162 (9)0.0124 (8)0.0018 (8)0.0017 (8)0.0051 (7)
C140.0146 (12)0.0130 (12)0.0145 (12)0.0018 (10)0.0030 (10)0.0000 (10)
C150.0169 (13)0.0226 (14)0.0157 (12)0.0009 (11)0.0013 (10)0.0001 (11)
C160.0161 (13)0.0159 (13)0.0253 (14)0.0028 (11)0.0015 (11)0.0001 (11)
C170.0186 (13)0.0147 (13)0.0185 (13)0.0003 (11)0.0043 (11)0.0037 (10)
N180.0154 (11)0.0158 (11)0.0149 (10)0.0021 (9)0.0014 (9)0.0024 (9)
C190.0178 (14)0.0174 (13)0.0129 (12)0.0044 (10)0.0002 (10)0.0010 (10)
C200.0240 (15)0.0246 (15)0.0145 (12)0.0016 (12)0.0000 (11)0.0031 (11)
O210.0222 (10)0.0258 (11)0.0174 (9)0.0043 (9)0.0053 (8)0.0016 (8)
C220.0134 (12)0.0141 (12)0.0138 (12)0.0002 (9)0.0009 (10)0.0006 (9)
C230.0142 (12)0.0151 (12)0.0170 (12)0.0021 (10)0.0036 (10)0.0020 (10)
C240.0157 (13)0.0128 (12)0.0154 (11)0.0006 (10)0.0011 (10)0.0019 (10)
C250.0119 (12)0.0135 (12)0.0211 (13)0.0012 (10)0.0009 (10)0.0011 (10)
C260.0135 (12)0.0166 (13)0.0168 (12)0.0010 (10)0.0058 (10)0.0027 (10)
C270.0165 (13)0.0170 (13)0.0119 (12)0.0009 (10)0.0003 (10)0.0017 (10)
O280.0164 (9)0.0216 (10)0.0145 (9)0.0060 (7)0.0035 (7)0.0066 (8)
C290.0164 (13)0.0228 (14)0.0148 (12)0.0023 (11)0.0010 (10)0.0032 (11)
C300.0268 (15)0.0302 (17)0.0184 (13)0.0063 (13)0.0041 (12)0.0073 (12)
O310.0162 (9)0.0227 (10)0.0195 (9)0.0066 (8)0.0036 (8)0.0019 (8)
C320.0131 (13)0.0297 (16)0.0203 (13)0.0067 (12)0.0020 (11)0.0050 (12)
I330.03570 (14)0.03570 (14)0.1759 (6)0.01778 (17)0.0541 (2)0.0541 (2)
C340.0191 (12)0.0191 (12)0.044 (3)0.0018 (16)0.0109 (14)0.0109 (14)
C350.0350 (18)0.046 (2)0.0254 (16)0.0116 (17)0.0016 (14)0.0091 (16)
C360.045 (2)0.0324 (18)0.0381 (19)0.0001 (15)0.0276 (17)0.0018 (15)
C370.0388 (19)0.0388 (19)0.074 (4)0.023 (2)0.035 (2)0.035 (2)
Geometric parameters (Å, º) top
S1—O21.442 (2)C20—H2010.956
S1—O31.448 (2)C20—H2030.962
S1—C41.759 (3)C20—H2020.961
S1—C51.769 (3)C22—C231.406 (4)
C4—H430.957C22—C271.385 (4)
C4—H420.963C23—C241.388 (4)
C4—H410.969C23—H2310.937
C5—C61.529 (3)C24—C251.410 (4)
C5—H510.966C24—O281.371 (3)
C5—H520.964C25—C261.388 (4)
C6—N71.477 (3)C25—O311.368 (3)
C6—C221.515 (4)C26—C271.392 (4)
C6—H610.975C26—H2610.929
N7—C81.396 (3)C27—H2710.931
N7—C111.396 (3)O28—C291.434 (3)
C8—C91.477 (4)C29—C301.507 (4)
C8—O121.217 (3)C29—H2910.983
C9—C101.393 (3)C29—H2920.970
C9—C141.397 (4)C30—H3020.957
C10—C111.489 (4)C30—H3010.962
C10—C171.373 (4)C30—H3030.960
C11—O131.215 (3)O31—C321.428 (3)
C14—C151.404 (4)C32—H3220.958
C14—N181.401 (3)C32—H3210.964
C15—C161.387 (4)C32—H3230.961
C15—H1510.930I33—C342.089 (4)
C16—C171.399 (4)C34—C35i1.371 (4)
C16—H1610.932C34—C351.371 (4)
C17—H1710.930C35—C361.430 (5)
N18—C191.375 (3)C35—H3510.942
N18—H1810.840 (17)C36—C371.359 (5)
C19—C201.498 (4)C36—H3610.919
C19—O211.220 (3)C37—H3710.930
O2—S1—O3117.88 (12)C19—C20—H201109.1
O2—S1—C4109.10 (14)C19—C20—H203109.9
O3—S1—C4108.58 (14)H201—C20—H203108.5
O2—S1—C5109.21 (12)C19—C20—H202111.4
O3—S1—C5108.95 (13)H201—C20—H202109.0
C4—S1—C5101.93 (13)H203—C20—H202108.9
S1—C4—H43109.7C6—C22—C23122.1 (2)
S1—C4—H42110.3C6—C22—C27119.1 (2)
H43—C4—H42108.6C23—C22—C27118.8 (2)
S1—C4—H41109.6C22—C23—C24120.8 (2)
H43—C4—H41109.4C22—C23—H231119.7
H42—C4—H41109.3C24—C23—H231119.5
S1—C5—C6114.35 (17)C23—C24—C25119.6 (2)
S1—C5—H51106.4C23—C24—O28124.0 (2)
C6—C5—H51108.4C25—C24—O28116.4 (2)
S1—C5—H52108.5C24—C25—C26119.4 (2)
C6—C5—H52108.7C24—C25—O31115.9 (2)
H51—C5—H52110.5C26—C25—O31124.8 (2)
C5—C6—N7111.4 (2)C25—C26—C27120.5 (2)
C5—C6—C22111.6 (2)C25—C26—H261119.5
N7—C6—C22112.3 (2)C27—C26—H261120.1
C5—C6—H61107.6C26—C27—C22120.9 (2)
N7—C6—H61106.4C26—C27—H271119.8
C22—C6—H61107.3C22—C27—H271119.3
C6—N7—C8123.7 (2)C24—O28—C29116.4 (2)
C6—N7—C11124.8 (2)O28—C29—C30108.5 (2)
C8—N7—C11111.3 (2)O28—C29—H291109.9
N7—C8—C9106.2 (2)C30—C29—H291109.0
N7—C8—O12125.1 (2)O28—C29—H292110.6
C9—C8—O12128.7 (2)C30—C29—H292109.7
C8—C9—C10108.8 (2)H291—C29—H292109.1
C8—C9—C14130.1 (2)C29—C30—H302109.1
C10—C9—C14121.2 (2)C29—C30—H301109.5
C9—C10—C11107.1 (2)H302—C30—H301109.8
C9—C10—C17122.6 (2)C29—C30—H303110.0
C11—C10—C17130.3 (2)H302—C30—H303109.2
C10—C11—N7106.7 (2)H301—C30—H303109.3
C10—C11—O13128.4 (2)C25—O31—C32116.0 (2)
N7—C11—O13124.9 (2)O31—C32—H322108.3
C9—C14—C15116.8 (2)O31—C32—H321110.4
C9—C14—N18117.6 (2)H322—C32—H321109.2
C15—C14—N18125.6 (2)O31—C32—H323109.7
C14—C15—C16120.6 (3)H322—C32—H323109.6
C14—C15—H151119.9H321—C32—H323109.8
C16—C15—H151119.5C35i—C34—I33119.3 (2)
C15—C16—C17122.6 (3)C35i—C34—C35121.5 (4)
C15—C16—H161118.9I33—C34—C35119.3 (2)
C17—C16—H161118.6C34—C35—C36119.4 (3)
C16—C17—C10116.2 (2)C34—C35—H351120.1
C16—C17—H171122.6C36—C35—H351120.4
C10—C17—H171121.2C35—C36—C37117.8 (4)
C14—N18—C19128.4 (2)C35—C36—H361121.0
C14—N18—H181115.0 (12)C37—C36—H361121.2
C19—N18—H181116.6 (12)C36i—C37—C36124.0 (5)
N18—C19—C20113.3 (2)C36i—C37—H371118.0
N18—C19—O21123.3 (3)C36—C37—H371118.0
C20—C19—O21123.3 (2)
Symmetry code: (i) y, x, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H51···O21ii0.972.523.471 (4)168
C5—H52···O130.962.483.096 (4)121
C5—H52···O13iii0.962.303.141 (4)145
C15—H151···O210.932.322.910 (4)121
C23—H231···O13iii0.942.433.365 (4)175
C26—H261···O2ii0.932.453.358 (4)166
C27—H271···O3ii0.932.553.261 (4)134
C32—H322···O21iv0.962.583.520 (4)167
C4—H43···O12v0.962.343.063 (4)132
N18—H181···O120.842.292.966 (4)138 (2)
C4—H42···O3iii0.962.553.379 (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, z1/4; (v) y1/2, x+3/2, z1/4.
(apremilastmesitilene) top
Crystal data top
2(C22H24N2O7S)·C9H12Dx = 1.387 Mg m3
Mr = 1041.17Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 62445 reflections
a = 13.2792 (1) Åθ = 5–68°
c = 28.2737 (1) ŵ = 1.58 mm1
V = 4985.70 (8) Å3T = 120 K
Z = 4Block, colorless
F(000) = 2199.9880.49 × 0.35 × 0.31 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4479 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.035
ω scansθmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.49, Tmax = 0.61k = 1515
90441 measured reflectionsl = 3333
4516 independent reflections
Refinement top
Refinement on F2H-atom parameters constrained
Least-squares matrix: full Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.04P)2 + 2.04P] ,
where P = (max(Fo2,0) + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.022(Δ/σ)max = 0.001
wR(F2) = 0.060Δρmax = 0.21 e Å3
S = 0.86Δρmin = 0.26 e Å3
4516 reflectionsExtinction correction: Larson (1970), Equation 22
337 parametersExtinction coefficient: 61 (8)
6 restraintsAbsolute structure: Flack (1983), 1862 Friedel-pairs
Primary atom site location: OtherAbsolute structure parameter: 0.003 (11)
Hydrogen site location: difference Fourier map
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.57862 (2)0.18236 (2)0.282453 (11)0.0204
O20.66730 (7)0.22420 (8)0.30443 (3)0.0263
O30.53532 (8)0.09343 (8)0.30348 (4)0.0296
C40.60449 (11)0.15805 (12)0.22253 (5)0.0287
C50.48529 (10)0.27773 (10)0.27897 (5)0.0199
C60.44358 (10)0.30955 (10)0.32720 (4)0.0192
N70.52323 (8)0.35398 (8)0.35716 (4)0.0188
C80.55573 (10)0.31021 (10)0.39949 (4)0.0184
C90.64526 (10)0.36763 (10)0.41484 (5)0.0184
C100.66422 (10)0.44234 (10)0.38152 (4)0.0193
C110.58556 (10)0.43403 (10)0.34421 (4)0.0189
O120.51551 (7)0.23868 (7)0.41875 (3)0.0226
O130.57507 (8)0.48496 (7)0.30884 (3)0.0243
C140.70448 (10)0.35641 (10)0.45493 (4)0.0194
C150.78599 (10)0.42293 (11)0.45998 (5)0.0233
C160.80428 (11)0.49674 (11)0.42596 (5)0.0246
C170.74369 (10)0.50871 (10)0.38608 (5)0.0226
N180.67762 (9)0.28104 (9)0.48739 (4)0.0211
C190.71998 (11)0.26047 (11)0.53052 (5)0.0232
C200.66192 (12)0.18431 (12)0.55886 (5)0.0287
O210.79692 (8)0.30058 (8)0.54498 (3)0.0287
C220.35211 (10)0.37771 (10)0.32180 (5)0.0194
C230.33704 (10)0.43779 (10)0.28178 (5)0.0207
C240.25140 (10)0.49712 (10)0.27760 (5)0.0212
C250.17836 (10)0.49566 (10)0.31376 (5)0.0219
C260.19388 (10)0.43612 (10)0.35331 (5)0.0228
C270.28041 (11)0.37748 (11)0.35718 (5)0.0223
O280.23129 (7)0.55953 (8)0.24018 (3)0.0268
C290.30457 (11)0.56389 (11)0.20284 (5)0.0243
C300.27799 (12)0.65034 (13)0.17106 (6)0.0351
O310.09501 (7)0.55421 (8)0.30633 (4)0.0277
C320.01938 (11)0.55043 (12)0.34229 (5)0.0279
C400.37984 (16)0.37984 (16)0.500000 (10)0.0938
C410.45912 (13)0.45912 (13)0.50000.0434
C420.46605 (12)0.52845 (14)0.46313 (6)0.0405
C430.53901 (12)0.60302 (12)0.46292 (5)0.0312
C440.60652 (12)0.60652 (12)0.500000 (7)0.0299
C450.54511 (17)0.67888 (16)0.42349 (7)0.0535
H510.51650.33630.26300.0241*
H520.43000.24970.26000.0236*
H610.42120.24720.34530.0234*
H2030.70400.15970.58450.0428*
H2020.60170.21710.57190.0433*
H2010.64280.12870.53840.0429*
H1510.83000.41940.48660.0278*
H1610.86160.54170.43020.0301*
H1710.75550.55990.36320.0274*
H2710.28940.33520.38500.0260*
H2610.14490.43410.37740.0265*
H3230.03690.59290.33290.0417*
H3210.04580.57740.37260.0419*
H3220.00350.48060.34690.0412*
H2310.38670.43890.25720.0240*
H2910.37290.57370.21630.0290*
H2920.30360.49940.18500.0297*
H3020.32680.65840.14540.0510*
H3010.27400.71310.18860.0508*
H3030.21320.63940.15460.0512*
H430.64000.21660.20940.0442*
H420.54090.14650.20610.0443*
H4410.65700.65700.50000.0351*
H4210.41950.52340.43740.0495*
H4510.47880.70950.41880.0812*
H4520.59260.73350.43230.0828*
H4530.56500.64730.39360.0819*
H4010.37280.32470.52640.1394*0.5000
H4020.30320.39400.50100.1407*0.5000
H4030.36880.32770.47240.1397*0.5000
H410.64630.09810.22150.0435*
H1810.62320.23880.47830.0254*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.01895 (16)0.02090 (17)0.02129 (15)0.00234 (12)0.00270 (12)0.00033 (12)
O20.0209 (5)0.0315 (5)0.0266 (5)0.0012 (4)0.0046 (4)0.0026 (4)
O30.0288 (5)0.0246 (5)0.0355 (5)0.0004 (4)0.0030 (4)0.0069 (4)
C40.0283 (8)0.0317 (8)0.0260 (7)0.0052 (6)0.0022 (6)0.0076 (6)
C50.0197 (6)0.0202 (6)0.0196 (6)0.0021 (5)0.0021 (5)0.0008 (5)
C60.0193 (7)0.0192 (6)0.0191 (6)0.0014 (5)0.0006 (5)0.0015 (5)
N70.0190 (5)0.0196 (5)0.0179 (5)0.0009 (4)0.0008 (4)0.0018 (4)
C80.0190 (6)0.0187 (6)0.0175 (6)0.0026 (5)0.0025 (5)0.0002 (5)
C90.0172 (6)0.0187 (6)0.0193 (6)0.0017 (5)0.0026 (5)0.0007 (5)
C100.0200 (6)0.0186 (6)0.0193 (6)0.0023 (5)0.0033 (5)0.0009 (5)
C110.0200 (6)0.0180 (6)0.0187 (6)0.0014 (5)0.0038 (5)0.0002 (5)
O120.0241 (5)0.0221 (5)0.0217 (5)0.0027 (4)0.0009 (4)0.0046 (4)
O130.0282 (5)0.0234 (5)0.0212 (5)0.0009 (4)0.0003 (4)0.0061 (4)
C140.0192 (6)0.0203 (6)0.0186 (6)0.0032 (5)0.0022 (5)0.0004 (5)
C150.0208 (7)0.0256 (7)0.0233 (6)0.0014 (6)0.0020 (5)0.0001 (6)
C160.0196 (7)0.0243 (7)0.0301 (7)0.0023 (5)0.0009 (6)0.0004 (6)
C170.0235 (7)0.0203 (7)0.0242 (7)0.0014 (5)0.0037 (5)0.0027 (5)
N180.0218 (6)0.0220 (6)0.0194 (5)0.0013 (4)0.0013 (5)0.0030 (5)
C190.0259 (7)0.0243 (7)0.0194 (6)0.0069 (6)0.0020 (6)0.0008 (6)
C200.0343 (8)0.0302 (8)0.0217 (7)0.0026 (7)0.0011 (6)0.0047 (6)
O210.0275 (5)0.0360 (6)0.0227 (5)0.0009 (5)0.0047 (4)0.0010 (4)
C220.0184 (6)0.0190 (6)0.0207 (6)0.0012 (5)0.0011 (5)0.0001 (5)
C230.0198 (6)0.0215 (7)0.0209 (6)0.0003 (5)0.0023 (5)0.0005 (5)
C240.0220 (6)0.0215 (7)0.0200 (6)0.0002 (5)0.0003 (5)0.0023 (5)
C250.0187 (6)0.0219 (7)0.0251 (7)0.0010 (5)0.0002 (5)0.0010 (5)
C260.0210 (7)0.0260 (7)0.0213 (6)0.0019 (5)0.0045 (5)0.0015 (5)
C270.0225 (7)0.0253 (7)0.0193 (6)0.0020 (5)0.0004 (5)0.0028 (5)
O280.0247 (5)0.0310 (6)0.0246 (5)0.0077 (4)0.0047 (4)0.0102 (4)
C290.0241 (7)0.0277 (7)0.0212 (6)0.0009 (6)0.0027 (5)0.0053 (5)
C300.0362 (9)0.0387 (9)0.0304 (8)0.0063 (7)0.0019 (7)0.0133 (7)
O310.0214 (5)0.0316 (5)0.0302 (5)0.0076 (4)0.0058 (4)0.0043 (4)
C320.0186 (7)0.0332 (8)0.0318 (7)0.0011 (6)0.0040 (6)0.0041 (6)
C400.0762 (16)0.0762 (16)0.129 (3)0.052 (2)0.071 (2)0.071 (2)
C410.0350 (8)0.0350 (8)0.0604 (16)0.0101 (10)0.0258 (9)0.0258 (9)
C420.0256 (8)0.0541 (11)0.0417 (9)0.0063 (7)0.0014 (7)0.0258 (9)
C430.0298 (8)0.0323 (8)0.0315 (8)0.0089 (6)0.0026 (7)0.0050 (6)
C440.0254 (6)0.0254 (6)0.0388 (12)0.0005 (8)0.0032 (6)0.0032 (6)
C450.0669 (13)0.0530 (12)0.0406 (10)0.0251 (10)0.0020 (9)0.0073 (9)
Geometric parameters (Å, º) top
S1—O21.4428 (10)C23—C241.3885 (19)
S1—O31.4418 (11)C23—H2310.959
S1—C41.7585 (14)C24—C251.4095 (19)
S1—C51.7747 (13)C24—O281.3702 (16)
C4—H430.982C25—C261.385 (2)
C4—H420.975C25—O311.3687 (16)
C4—H410.971C26—C271.392 (2)
C5—C61.5312 (18)C26—H2610.942
C5—H510.990C27—H2710.973
C5—H520.982O28—C291.4370 (16)
C6—N71.4780 (16)C29—C301.500 (2)
C6—C221.5226 (18)C29—H2910.993
C6—H611.018C29—H2920.994
N7—C81.3987 (17)C30—H3020.978
N7—C111.3960 (17)C30—H3010.971
C8—C91.4775 (18)C30—H3030.990
C8—O121.2182 (16)O31—C321.4301 (17)
C9—C101.3912 (18)C32—H3230.973
C9—C141.3875 (18)C32—H3210.994
C10—C111.4884 (18)C32—H3220.985
C10—C171.3810 (19)C40—H403i1.053
C11—O131.2153 (16)C40—H401i1.050
C14—C151.4044 (19)C40—H402i1.036
C14—N181.4040 (17)C40—C411.489 (4)
C15—C161.395 (2)C40—H4011.050
C15—H1510.954C40—H4021.036
C16—C171.394 (2)C40—H4031.053
C16—H1610.975C41—C42i1.394 (2)
C17—H1710.951C41—C421.394 (2)
N18—C191.3707 (17)C42—C431.385 (2)
N18—H1810.950C42—H4210.956
C19—C201.503 (2)C43—C441.3801 (19)
C19—O211.2225 (18)C43—C451.505 (2)
C20—H2030.973C44—H4410.948
C20—H2020.982C45—H4510.978
C20—H2010.972C45—H4520.993
C22—C231.3990 (18)C45—H4530.979
C22—C271.3808 (19)
O2—S1—O3117.60 (6)C23—C24—O28124.65 (12)
O2—S1—C4109.03 (7)C25—C24—O28115.74 (12)
O3—S1—C4108.96 (7)C24—C25—C26119.41 (12)
O2—S1—C5108.61 (6)C24—C25—O31115.93 (12)
O3—S1—C5109.20 (6)C26—C25—O31124.65 (12)
C4—S1—C5102.35 (7)C25—C26—C27120.36 (12)
S1—C4—H43108.3C25—C26—H261119.9
S1—C4—H42108.5C27—C26—H261119.8
H43—C4—H42111.1C26—C27—C22120.72 (13)
S1—C4—H41106.9C26—C27—H271119.1
H43—C4—H41111.3C22—C27—H271120.2
H42—C4—H41110.6C24—O28—C29117.36 (10)
S1—C5—C6113.58 (9)O28—C29—C30108.15 (12)
S1—C5—H51107.1O28—C29—H291110.0
C6—C5—H51109.9C30—C29—H291110.2
S1—C5—H52106.4O28—C29—H292109.2
C6—C5—H52108.6C30—C29—H292110.7
H51—C5—H52111.2H291—C29—H292108.7
C5—C6—N7111.21 (10)C29—C30—H302111.8
C5—C6—C22111.31 (10)C29—C30—H301111.3
N7—C6—C22113.02 (10)H302—C30—H301108.7
C5—C6—H61109.3C29—C30—H303112.0
N7—C6—H61104.2H302—C30—H303104.1
C22—C6—H61107.5H301—C30—H303108.6
C6—N7—C8123.04 (11)C25—O31—C32116.03 (11)
C6—N7—C11125.31 (11)O31—C32—H323109.0
C8—N7—C11110.97 (11)O31—C32—H321110.7
N7—C8—C9106.57 (11)H323—C32—H321107.3
N7—C8—O12124.84 (12)O31—C32—H322110.2
C9—C8—O12128.59 (12)H323—C32—H322110.2
C8—C9—C10108.34 (11)H321—C32—H322109.5
C8—C9—C14129.84 (12)H403i—C40—H401i93.2
C10—C9—C14121.81 (12)H403i—C40—H402i90.1
C9—C10—C11107.46 (11)H401i—C40—H402i91.1
C9—C10—C17122.02 (12)H403i—C40—C41124.3
C11—C10—C17130.52 (12)H401i—C40—C41123.8
C10—C11—N7106.66 (11)H402i—C40—C41124.5
C10—C11—O13128.48 (12)H403i—C40—H40147.0
N7—C11—O13124.86 (12)H401i—C40—H401112.3
C9—C14—C15116.90 (12)H402i—C40—H40149.4
C9—C14—N18117.80 (12)C41—C40—H401123.8
C15—C14—N18125.29 (12)H403i—C40—H40250.2
C14—C15—C16120.40 (13)H401i—C40—H40249.4
C14—C15—H151121.4H402i—C40—H402111.0
C16—C15—H151118.1C41—C40—H402124.5
C15—C16—C17122.51 (13)H401—C40—H40291.1
C15—C16—H161118.8H403i—C40—H403111.5
C17—C16—H161118.7H401i—C40—H40347.0
C16—C17—C10116.34 (12)H402i—C40—H40350.2
C16—C17—H171122.4C41—C40—H403124.3
C10—C17—H171121.2H401—C40—H40393.2
C14—N18—C19128.28 (12)H402—C40—H40390.1
C14—N18—H181115.9C40—C41—C42i120.91 (11)
C19—N18—H181115.8C40—C41—C42120.91 (11)
N18—C19—C20113.44 (12)C42i—C41—C42118.2 (2)
N18—C19—O21123.62 (13)C41—C42—C43121.42 (17)
C20—C19—O21122.93 (12)C41—C42—H421118.7
C19—C20—H203109.2C43—C42—H421119.9
C19—C20—H202108.6C42—C43—C44118.37 (16)
H203—C20—H202109.6C42—C43—C45121.27 (16)
C19—C20—H201109.1C44—C43—C45120.35 (17)
H203—C20—H201109.8C43—C44—C43i122.2 (2)
H202—C20—H201110.4C43—C44—H441118.9
C6—C22—C23122.28 (11)C43i—C44—H441118.9
C6—C22—C27118.44 (12)C43—C45—H451109.2
C23—C22—C27119.25 (12)C43—C45—H452109.8
C22—C23—C24120.64 (12)H451—C45—H452107.6
C22—C23—H231119.8C43—C45—H453111.5
C24—C23—H231119.5H451—C45—H453107.7
C23—C24—C25119.61 (12)H452—C45—H453110.9
Symmetry code: (i) y, x, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H51···O130.992.493.116 (2)121
C5—H51···O13ii0.992.353.185 (2)142
C5—H52···O21iii0.982.453.422 (2)172
C27—H271···O2iii0.972.493.213 (2)131
C26—H261···O3iii0.942.463.396 (2)170
C23—H231···O13ii0.962.533.490 (2)175
C4—H43···O2ii0.982.403.337 (2)158
C40—H401···O2iv1.052.583.499 (2)146
C4—H41···O12v0.972.453.286 (2)144
N18—H181···O120.952.212.952 (2)134
Symmetry codes: (ii) y+1, x+1, z+1/2; (iii) x1/2, y+1/2, z+3/4; (iv) y+1/2, x1/2, z+1/4; (v) y+1/2, x+1/2, z1/4.
(apremilastmetaxylene) top
Crystal data top
C22H24N2O7S·0.5(C8H10)Dx = 1.387 Mg m3
Mr = 513.59Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 69131 reflections
a = 12.9696 (1) Åθ = 5–68°
c = 29.2499 (1) ŵ = 1.59 mm1
V = 4920.14 (8) Å3T = 120 K
Z = 8Block, colorless
F(000) = 21680.33 × 0.28 × 0.25 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4439 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.037
ω scansθmax = 67.6°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.56, Tmax = 0.68k = 1515
100964 measured reflectionsl = 3234
4454 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.036 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.02P)2 + 6.16P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.091(Δ/σ)max = 0.001
S = 1.12Δρmax = 0.20 e Å3
4453 reflectionsΔρmin = 0.23 e Å3
362 parametersAbsolute structure: Flack (1983), 1832 Friedel-pairs
125 restraintsAbsolute structure parameter: 0.03 (2)
Primary atom site location: Other
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
C400.6710 (6)0.5593 (6)0.5661 (3)0.05940.5000
C410.4691 (7)0.5885 (6)0.4199 (3)0.06020.5000
C420.4860 (6)0.5383 (6)0.4649 (3)0.04480.5000
C430.5667 (19)0.571 (2)0.4928 (5)0.03730.5000
C440.5815 (5)0.5255 (5)0.5356 (2)0.04340.5000
C450.5155 (6)0.4481 (5)0.5503 (3)0.04250.5000
C460.4358 (17)0.4139 (17)0.5219 (7)0.04630.5000
C470.4215 (17)0.4588 (18)0.4792 (6)0.04630.5000
S10.59258 (5)0.16872 (5)0.28452 (2)0.0212
O20.68444 (14)0.21493 (14)0.30385 (6)0.0283
O30.54917 (15)0.08080 (14)0.30775 (7)0.0296
C40.6189 (2)0.1357 (2)0.22751 (9)0.0327
C50.49641 (19)0.26539 (19)0.27892 (8)0.0200
C60.45191 (19)0.29989 (19)0.32485 (8)0.0193
N70.53234 (16)0.34636 (15)0.35428 (7)0.0185
C80.56145 (19)0.30486 (18)0.39650 (8)0.0184
C90.65096 (19)0.36583 (19)0.41219 (8)0.0183
C100.6736 (2)0.43869 (19)0.37903 (8)0.0201
C110.59690 (19)0.42708 (18)0.34173 (8)0.0190
O120.51867 (14)0.23342 (13)0.41545 (6)0.0228
O130.58875 (15)0.47698 (13)0.30636 (6)0.0250
C140.70720 (19)0.35921 (18)0.45244 (8)0.0187
C150.78905 (19)0.4284 (2)0.45773 (9)0.0245
C160.8115 (2)0.5000 (2)0.42382 (10)0.0274
C170.7539 (2)0.5079 (2)0.38358 (9)0.0245
N180.67714 (17)0.28524 (16)0.48458 (7)0.0224
C190.7192 (2)0.2664 (2)0.52696 (9)0.0242
C200.6582 (2)0.1912 (2)0.55505 (9)0.0321
O210.79719 (14)0.30845 (15)0.54103 (6)0.0296
C220.35946 (19)0.37069 (19)0.31878 (8)0.0201
C230.34297 (19)0.42797 (19)0.27877 (9)0.0229
C240.2569 (2)0.4900 (2)0.27427 (9)0.0244
C250.1834 (2)0.49466 (19)0.30987 (9)0.0241
C260.2001 (2)0.4383 (2)0.34941 (9)0.0246
C270.2879 (2)0.3768 (2)0.35362 (9)0.0226
O280.23479 (14)0.55103 (16)0.23704 (7)0.0320
C290.3117 (2)0.5567 (2)0.20161 (10)0.0342
C300.2841 (3)0.6454 (3)0.17110 (13)0.0529
O310.09927 (14)0.55572 (15)0.30243 (7)0.0317
C320.0267 (2)0.5629 (3)0.33924 (10)0.0379
H520.44170.23770.26010.0242*
H510.52720.32490.26380.0237*
H610.42670.23710.34120.0219*
H2010.70120.16780.58040.0471*
H2030.63970.13370.53500.0469*
H2020.59680.22480.56640.0476*
H1510.82880.42650.48370.0278*
H1610.86700.54410.42790.0325*
H1710.76930.55650.36110.0307*
H2710.29700.33750.38040.0249*
H2610.15250.44220.37380.0286*
H3210.02770.60920.33050.0530*
H3220.00010.49610.34650.0531*
H3230.06020.59070.36650.0525*
H2310.39190.42430.25360.0256*
H2920.31310.49210.18600.0404*
H2910.37790.56820.21600.0402*
H3010.34150.65500.14970.0700*
H3030.22270.62960.15370.0699*
H3020.27430.70690.18910.0693*
H430.55310.11840.21460.0500*
H420.66360.07700.22850.0499*
H410.65010.19460.21340.0500*
H4110.41100.55840.40530.0759*0.5000
H4120.45710.66000.42430.0759*0.5000
H4130.52850.57920.40130.0759*0.5000
H4010.66990.52210.59410.0711*0.5000
H4020.66560.63110.57220.0711*0.5000
H4030.73380.54590.55050.0711*0.5000
H4310.61270.62300.48240.0457*0.5000
H4510.52450.41750.57980.0513*0.5000
H4610.39120.36030.53180.0536*0.5000
H4710.36750.43560.45980.0566*0.5000
H1810.62070.24270.47610.0276*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C400.044 (4)0.049 (4)0.085 (6)0.009 (3)0.007 (4)0.024 (4)
C410.062 (5)0.050 (4)0.069 (5)0.028 (4)0.013 (4)0.003 (4)
C420.036 (6)0.045 (6)0.054 (5)0.011 (4)0.003 (4)0.019 (5)
C430.029 (5)0.031 (6)0.051 (11)0.007 (3)0.005 (7)0.012 (6)
C440.037 (5)0.023 (4)0.070 (5)0.009 (3)0.017 (4)0.013 (4)
C450.040 (5)0.028 (4)0.060 (6)0.018 (4)0.020 (4)0.011 (4)
C460.029 (8)0.034 (6)0.076 (8)0.006 (3)0.008 (5)0.021 (5)
C470.029 (5)0.045 (10)0.065 (7)0.001 (5)0.009 (5)0.020 (6)
S10.0220 (3)0.0220 (3)0.0196 (3)0.0039 (2)0.0020 (2)0.0027 (2)
O20.0218 (9)0.0348 (11)0.0281 (10)0.0021 (8)0.0053 (8)0.0032 (8)
O30.0325 (10)0.0229 (9)0.0335 (10)0.0038 (8)0.0006 (8)0.0029 (8)
C40.0323 (16)0.0377 (16)0.0281 (14)0.0056 (12)0.0038 (12)0.0103 (12)
C50.0204 (12)0.0208 (12)0.0190 (11)0.0041 (9)0.0013 (10)0.0008 (10)
C60.0204 (12)0.0206 (12)0.0169 (11)0.0002 (10)0.0010 (10)0.0001 (9)
N70.0215 (11)0.0172 (10)0.0167 (10)0.0006 (8)0.0012 (8)0.0022 (8)
C80.0215 (12)0.0184 (12)0.0155 (11)0.0044 (10)0.0030 (9)0.0019 (9)
C90.0184 (12)0.0185 (12)0.0180 (12)0.0028 (9)0.0046 (9)0.0017 (9)
C100.0229 (13)0.0175 (12)0.0198 (11)0.0023 (10)0.0042 (10)0.0008 (9)
C110.0209 (12)0.0166 (12)0.0196 (12)0.0015 (10)0.0044 (10)0.0007 (10)
O120.0251 (9)0.0215 (9)0.0218 (9)0.0048 (7)0.0022 (7)0.0033 (7)
O130.0330 (10)0.0222 (9)0.0197 (9)0.0007 (8)0.0024 (8)0.0056 (7)
C140.0207 (12)0.0172 (12)0.0182 (12)0.0055 (10)0.0024 (9)0.0002 (9)
C150.0223 (13)0.0252 (14)0.0260 (13)0.0009 (11)0.0013 (10)0.0009 (10)
C160.0215 (13)0.0226 (13)0.0380 (15)0.0044 (11)0.0009 (12)0.0038 (11)
C170.0260 (14)0.0211 (13)0.0263 (14)0.0017 (11)0.0020 (11)0.0050 (11)
N180.0218 (11)0.0254 (11)0.0200 (10)0.0047 (9)0.0005 (9)0.0021 (9)
C190.0263 (14)0.0267 (14)0.0197 (12)0.0041 (11)0.0011 (11)0.0017 (11)
C200.0341 (16)0.0408 (17)0.0216 (13)0.0032 (13)0.0005 (12)0.0068 (12)
O210.0291 (10)0.0375 (11)0.0224 (9)0.0044 (9)0.0023 (8)0.0006 (8)
C220.0200 (13)0.0192 (12)0.0211 (12)0.0021 (10)0.0004 (10)0.0006 (10)
C230.0220 (13)0.0215 (13)0.0250 (12)0.0019 (10)0.0071 (10)0.0045 (10)
C240.0195 (12)0.0249 (14)0.0290 (13)0.0005 (10)0.0023 (10)0.0071 (11)
C250.0191 (12)0.0199 (13)0.0333 (14)0.0021 (10)0.0025 (11)0.0030 (11)
C260.0211 (13)0.0258 (14)0.0268 (13)0.0040 (10)0.0062 (11)0.0038 (11)
C270.0248 (14)0.0237 (13)0.0192 (12)0.0030 (10)0.0031 (10)0.0012 (10)
O280.0217 (10)0.0366 (11)0.0378 (11)0.0063 (8)0.0067 (8)0.0180 (9)
C290.0250 (14)0.0444 (17)0.0332 (15)0.0011 (13)0.0040 (12)0.0197 (13)
C300.0320 (17)0.068 (3)0.059 (2)0.0053 (16)0.0048 (16)0.042 (2)
O310.0209 (9)0.0331 (11)0.0410 (11)0.0076 (8)0.0072 (8)0.0018 (9)
C320.0209 (14)0.058 (2)0.0349 (16)0.0093 (14)0.0031 (12)0.0188 (14)
Geometric parameters (Å, º) top
C40—C41i1.638 (12)C8—C91.478 (3)
C40—C441.528 (9)C8—O121.214 (3)
C40—H4010.950C9—C101.386 (3)
C40—H4020.950C9—C141.388 (3)
C40—H4030.950C10—C111.484 (3)
C41—H451i1.066C10—C171.381 (4)
C41—C44i1.497 (11)C11—O131.225 (3)
C41—C45i1.315 (12)C14—C151.398 (4)
C41—C421.485 (12)C14—N181.399 (3)
C41—H4110.950C15—C161.390 (4)
C41—H4120.950C15—H1510.919
C41—H4130.950C16—C171.398 (4)
C42—C46i1.671 (12)C16—H1610.926
C42—C43i1.697 (11)C17—H1710.933
C42—C431.393 (7)N18—C191.376 (3)
C42—C471.393 (7)N18—H1810.950
C43—H431i1.161C19—C201.500 (4)
C43—C44i0.996 (15)C19—O211.220 (3)
C43—C441.395 (6)C20—H2010.976
C43—H4310.950C20—H2030.979
C44—C451.388 (6)C20—H2020.967
C45—C47i1.187 (19)C22—C231.403 (3)
C45—C461.399 (7)C22—C271.381 (3)
C45—H4510.956C23—C241.382 (4)
C46—C46i1.34 (3)C23—H2310.972
C46—H471i0.806C24—C251.413 (4)
C46—C471.389 (6)C24—O281.377 (3)
C46—H4610.950C25—C261.385 (4)
C47—H461i1.226C25—O311.365 (3)
C47—C47i1.39 (2)C26—C271.395 (4)
C47—H4710.951C26—H2610.946
S1—O21.4485 (19)C27—H2710.943
S1—O31.442 (2)O28—C291.440 (3)
S1—C41.755 (3)C29—C301.499 (4)
S1—C51.776 (2)C29—H2920.954
C4—H430.959C29—H2910.968
C4—H420.958C30—H3010.981
C4—H410.958C30—H3030.966
C5—C61.529 (3)C30—H3020.964
C5—H520.968O31—C321.433 (3)
C5—H510.975C32—H3210.960
C6—N71.481 (3)C32—H3220.958
C6—C221.521 (3)C32—H3230.976
C6—H610.999H411—H451i0.626
N7—C81.399 (3)H461—H471i0.633
N7—C111.390 (3)
C41i—C40—C4456.3 (5)O2—S1—O3117.68 (11)
C41i—C40—H40154.0O2—S1—C4108.19 (13)
C44—C40—H401110.3O3—S1—C4109.30 (14)
C41i—C40—H402127.2O2—S1—C5108.75 (12)
C44—C40—H402109.6O3—S1—C5109.12 (12)
H401—C40—H402109.5C4—S1—C5102.76 (12)
C41i—C40—H403123.4S1—C4—H43105.0
C44—C40—H403108.6S1—C4—H42106.4
H401—C40—H403109.5H43—C4—H42111.4
H402—C40—H403109.5S1—C4—H41107.2
H451i—C41—C44i104.6H43—C4—H41113.2
H451i—C41—C40i162.7H42—C4—H41113.0
C44i—C41—C40i58.1 (5)S1—C5—C6112.98 (16)
H451i—C41—C45i45.9S1—C5—H52107.8
C44i—C41—C45i58.7 (4)C6—C5—H52109.4
C40i—C41—C45i116.9 (7)S1—C5—H51108.2
H451i—C41—C4275.2C6—C5—H51108.8
C44i—C41—C4229.5 (3)H52—C5—H51109.6
C40i—C41—C4287.6 (6)C5—C6—N7111.3 (2)
C45i—C41—C4229.3 (3)C5—C6—C22111.82 (19)
H451i—C41—H41135.6N7—C6—C22112.18 (19)
C44i—C41—H411139.0C5—C6—H61107.8
C40i—C41—H411161.4N7—C6—H61106.5
C45i—C41—H41180.7C22—C6—H61106.8
C42—C41—H411109.7C6—N7—C8123.1 (2)
H451i—C41—H412131.1C6—N7—C11125.3 (2)
C44i—C41—H41291.2C8—N7—C11111.1 (2)
C40i—C41—H41256.2N7—C8—C9106.3 (2)
C45i—C41—H412125.4N7—C8—O12125.0 (2)
C42—C41—H412109.3C9—C8—O12128.7 (2)
H451i—C41—H413114.6C8—C9—C10108.3 (2)
C44i—C41—H41395.4C8—C9—C14130.0 (2)
C40i—C41—H41369.3C10—C9—C14121.6 (2)
C45i—C41—H413117.1C9—C10—C11107.7 (2)
C42—C41—H413109.4C9—C10—C17122.4 (2)
H411—C41—H412109.5C11—C10—C17129.9 (2)
H411—C41—H413109.5C10—C11—N7106.61 (19)
H412—C41—H413109.5C10—C11—O13128.7 (2)
C41—C42—C46i118.1 (7)N7—C11—O13124.7 (2)
C41—C42—C43i130.4 (7)C9—C14—C15116.9 (2)
C46i—C42—C43i111.5 (8)C9—C14—N18117.8 (2)
C41—C42—C43119.9 (6)C15—C14—N18125.3 (2)
C46i—C42—C43121.8 (8)C14—C15—C16120.6 (2)
C43i—C42—C4311.2 (10)C14—C15—H151120.0
C41—C42—C47120.1 (6)C16—C15—H151119.4
C46i—C42—C476 (2)C15—C16—C17122.5 (2)
C43i—C42—C47109.3 (4)C15—C16—H161118.9
C43—C42—C47119.98 (9)C17—C16—H161118.5
H431i—C43—C42168.1C16—C17—C10115.9 (2)
H431i—C43—C42i89.1C16—C17—H171122.0
C42—C43—C42i93.9 (5)C10—C17—H171122.2
H431i—C43—C44i142.4C14—N18—C19128.1 (2)
C42—C43—C44i31.9 (5)C14—N18—H181115.9
C42i—C43—C44i125.4 (3)C19—N18—H181116.0
H431i—C43—C4463.4N18—C19—C20113.6 (2)
C42—C43—C44120.01 (9)N18—C19—O21123.5 (2)
C42i—C43—C4426.2 (5)C20—C19—O21122.9 (2)
C44i—C43—C44151.4 (7)C19—C20—H201108.5
H431i—C43—H43158.3C19—C20—H203107.2
C42—C43—H431120.0H201—C20—H203111.0
C42i—C43—H431146.1C19—C20—H202109.2
C44i—C43—H43188.5H201—C20—H202110.5
C44—C43—H431120.0H203—C20—H202110.3
C40—C44—C41i65.6 (5)C6—C22—C23122.5 (2)
C40—C44—C43120.4 (5)C6—C22—C27118.6 (2)
C41i—C44—C43174.0 (6)C23—C22—C27118.9 (2)
C40—C44—C43i115.9 (6)C22—C23—C24120.7 (2)
C41i—C44—C43i174 (2)C22—C23—H231120.4
C43—C44—C43i7 (3)C24—C23—H231118.9
C40—C44—C45119.6 (5)C23—C24—C25120.0 (2)
C41i—C44—C4554.0 (5)C23—C24—O28125.3 (2)
C43—C44—C45119.97 (9)C25—C24—O28114.7 (2)
C43i—C44—C45124.2 (5)C24—C25—C26119.1 (2)
C44—C45—C41i67.2 (6)C24—C25—O31116.5 (2)
C44—C45—C47i111.5 (6)C26—C25—O31124.4 (2)
C41i—C45—C47i171.6 (18)C25—C26—C27120.2 (2)
C44—C45—C46119.97 (9)C25—C26—H261120.0
C41i—C45—C46172.5 (7)C27—C26—H261119.8
C47i—C45—C4610 (2)C26—C27—C22121.1 (2)
C44—C45—H451120.4C26—C27—H271119.0
C41i—C45—H45153.2C22—C27—H271119.9
C47i—C45—H451127.7C24—O28—C29117.0 (2)
C46—C45—H451119.7O28—C29—C30107.6 (2)
C42i—C46—C4525.4 (4)O28—C29—H292108.3
C42i—C46—C46i105.7 (7)C30—C29—H292113.1
C45—C46—C46i131.1 (7)O28—C29—H291108.0
C42i—C46—H471i105.5C30—C29—H291110.7
C45—C46—H471i81.0H292—C29—H291109.0
C46i—C46—H471i142.4C29—C30—H301107.2
C42i—C46—C4794.6 (4)C29—C30—H303110.4
C45—C46—C47120.01 (9)H301—C30—H303108.5
C46i—C46—C4713.1 (13)C29—C30—H302110.0
H471i—C46—C47155.5H301—C30—H302110.0
C42i—C46—H461145.4H303—C30—H302110.8
C45—C46—H461120.0C25—O31—C32116.3 (2)
C46i—C46—H461108.5O31—C32—H321108.9
H471i—C46—H46141.2O31—C32—H322110.2
C47—C46—H461120.0H321—C32—H322111.0
H461i—C47—C47i101.9O31—C32—H323110.2
H461i—C47—C42147.1H321—C32—H323108.3
C47i—C47—C42108.1 (4)H322—C32—H323108.3
H461i—C47—C4691.3H451i—H411—C4182.3
C47i—C47—C4613.0 (12)C43i—H431—C4320.4
C42—C47—C46120.02 (9)H411i—H451—C41i62.1
H461i—C47—C45i116.1H411i—H451—C45140.5
C47i—C47—C45i138.5 (11)C41i—H451—C4580.9
C42—C47—C45i31.4 (4)H471i—H461—C47i49.9
C46—C47—C45i151.1 (5)H471i—H461—C4657.1
H461i—C47—H47130.6C47i—H461—C468.2
C47i—C47—H471131.8H461i—H471—C4799.5
C42—C47—H471119.8H461i—H471—C46i81.7
C46—C47—H471120.2C47—H471—C46i18.4
C45i—C47—H47188.6
Symmetry code: (i) y, x, z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H52···O21ii0.972.473.432 (8)172
C5—H51···O130.982.473.100 (8)122
C5—H51···O13iii0.982.343.149 (8)140
C15—H151···O210.922.312.892 (8)121
C27—H271···O2ii0.942.513.247 (8)135
C26—H261···O3ii0.952.433.357 (8)168
C23—H231···O13iii0.972.453.420 (8)176
C4—H42···O12iv0.962.403.084 (8)128
C4—H41···O2iii0.962.403.306 (8)157
C43i—H431···C40i1.161.702.538 (8)124
N18—H181···O120.952.222.961 (8)135
Symmetry codes: (i) y, x, z+1; (ii) x1/2, y+1/2, z+3/4; (iii) y+1, x+1, z+1/2; (iv) y+1/2, x+1/2, z1/4.
(apremilastnicotinamide) top
Crystal data top
2(C22H24N2O7S)·C6H4N2ODx = 1.413 Mg m3
Mr = 1041.12Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 57694 reflections
a = 12.8876 (1) Åθ = 4–68°
c = 29.4547 (2) ŵ = 1.64 mm1
V = 4892.14 (8) Å3T = 120 K
Z = 4Block, colorless
F(000) = 2183.9890.32 × 0.24 × 0.16 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4359 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.039
ω scansθmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.60, Tmax = 0.77k = 1515
90858 measured reflectionsl = 3535
4429 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.039 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.05P)2 + 4.21P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.106(Δ/σ)max = 0.001
S = 1.02Δρmax = 0.54 e Å3
4429 reflectionsΔρmin = 0.47 e Å3
350 parametersAbsolute structure: Flack (1983), 1816 Friedel-pairs
57 restraintsAbsolute structure parameter: 0.01 (2)
Primary atom site location: Other
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.40408 (5)0.16284 (5)0.46354 (2)0.0286
O20.31159 (15)0.21130 (15)0.44569 (7)0.0351
O30.44578 (16)0.07561 (15)0.43907 (7)0.0375
C40.3796 (3)0.1259 (3)0.51985 (10)0.0430
C50.5017 (2)0.2588 (2)0.46997 (8)0.0270
C60.5461 (2)0.2969 (2)0.42483 (8)0.0258
N70.46516 (16)0.34458 (16)0.39623 (7)0.0252
C80.43716 (19)0.30687 (19)0.35368 (8)0.0252
C90.3461 (2)0.36864 (19)0.33869 (8)0.0253
C100.3231 (2)0.43952 (19)0.37260 (8)0.0274
C110.3991 (2)0.42444 (19)0.40975 (8)0.0262
O120.48091 (14)0.23567 (14)0.33384 (6)0.0306
O130.40556 (15)0.47053 (14)0.44576 (6)0.0317
C140.2906 (2)0.36469 (19)0.29837 (9)0.0266
C150.2087 (2)0.4351 (2)0.29409 (9)0.0301
C160.1857 (2)0.5046 (2)0.32857 (10)0.0342
C170.2429 (2)0.5096 (2)0.36865 (9)0.0312
N180.32153 (17)0.29309 (17)0.26523 (7)0.0286
C190.2800 (2)0.2761 (2)0.22329 (9)0.0293
C200.3422 (2)0.2023 (2)0.19433 (9)0.0369
O210.20092 (15)0.31738 (16)0.20995 (6)0.0364
C220.6385 (2)0.3688 (2)0.43224 (9)0.0271
C230.6525 (2)0.4236 (2)0.47291 (9)0.0282
C240.7385 (2)0.4876 (2)0.47889 (9)0.0298
C250.8116 (2)0.4964 (2)0.44365 (10)0.0315
C260.7968 (2)0.4426 (2)0.40369 (9)0.0337
C270.7109 (2)0.3789 (2)0.39814 (9)0.0310
O280.75763 (15)0.54457 (16)0.51723 (7)0.0373
C290.6807 (2)0.5400 (2)0.55255 (10)0.0384
C300.7104 (3)0.6157 (3)0.58912 (13)0.0586
O310.89513 (15)0.56018 (16)0.45259 (7)0.0407
C320.9653 (3)0.5761 (3)0.41558 (11)0.0537
C340.5391 (6)0.5197 (6)0.2961 (3)0.1355
C350.4586 (5)0.5701 (5)0.2713 (2)0.1239
C360.4092 (9)0.6550 (9)0.2898 (4)0.14660.5000
N370.3342 (11)0.7152 (11)0.2646 (5)0.16970.5000
O380.4246 (11)0.6777 (10)0.3310 (5)0.21340.5000
H2010.30340.18140.16880.0554*
H2030.40320.23400.18390.0548*
H2020.36180.14240.21080.0541*
H1810.37130.25490.27210.0340*
H1710.22940.55900.39140.0366*
H1610.12900.55180.32480.0414*
H1510.17030.43750.26770.0358*
H3211.01860.62390.42620.0790*
H3230.93010.60650.38990.0796*
H3220.99920.51010.40680.0799*
H2310.60380.41630.49630.0328*
H3020.65690.61830.61200.0890*
H3010.77460.59480.60290.0885*
H3030.71840.68170.57430.0884*
H2920.61540.56140.53980.0459*
H2910.67280.46890.56420.0453*
H2610.84500.44740.38080.0405*
H2710.70050.34260.37070.0361*
H610.56950.23690.40810.0302*
H520.55720.22540.48640.0325*
H510.47080.31600.48710.0317*
H410.44060.09530.53230.0638*
H430.32530.07550.51810.0642*
H420.35680.18480.53720.0632*
H3310.65320.40200.30080.1357*0.5000
H3410.55460.54040.32780.1617*
H3510.42580.62900.28430.1523*0.5000
C330.5931 (5)0.4348 (5)0.2723 (2)0.12470.5000
N1330.5944 (5)0.4384 (5)0.2720 (2)0.12950.5000
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0297 (3)0.0275 (3)0.0286 (3)0.0049 (2)0.0009 (2)0.0020 (3)
O20.0292 (10)0.0391 (11)0.0371 (10)0.0027 (8)0.0059 (8)0.0010 (8)
O30.0387 (11)0.0296 (10)0.0442 (11)0.0036 (8)0.0005 (9)0.0039 (8)
C40.0449 (17)0.0479 (18)0.0362 (15)0.0062 (14)0.0029 (13)0.0124 (13)
C50.0274 (13)0.0279 (13)0.0256 (12)0.0030 (10)0.0022 (10)0.0018 (10)
C60.0273 (12)0.0257 (12)0.0245 (12)0.0018 (10)0.0011 (10)0.0013 (10)
N70.0275 (11)0.0249 (10)0.0232 (10)0.0004 (9)0.0024 (8)0.0015 (8)
C80.0253 (12)0.0261 (12)0.0243 (11)0.0015 (10)0.0029 (10)0.0004 (10)
C90.0264 (12)0.0230 (12)0.0265 (12)0.0022 (10)0.0051 (10)0.0001 (9)
C100.0281 (13)0.0254 (12)0.0286 (12)0.0030 (10)0.0063 (10)0.0017 (10)
C110.0286 (12)0.0236 (12)0.0264 (12)0.0022 (10)0.0048 (10)0.0004 (10)
O120.0319 (10)0.0315 (10)0.0284 (9)0.0060 (8)0.0018 (7)0.0062 (8)
O130.0382 (10)0.0288 (9)0.0281 (9)0.0002 (8)0.0028 (8)0.0062 (8)
C140.0265 (13)0.0247 (12)0.0286 (13)0.0027 (10)0.0031 (10)0.0005 (10)
C150.0262 (13)0.0285 (13)0.0357 (14)0.0012 (10)0.0006 (11)0.0015 (11)
C160.0293 (14)0.0294 (14)0.0437 (15)0.0066 (11)0.0003 (12)0.0036 (12)
C170.0328 (14)0.0263 (13)0.0346 (14)0.0015 (11)0.0047 (11)0.0043 (11)
N180.0255 (11)0.0312 (11)0.0293 (11)0.0057 (9)0.0009 (9)0.0053 (9)
C190.0299 (14)0.0309 (13)0.0271 (13)0.0029 (11)0.0011 (10)0.0024 (11)
C200.0380 (15)0.0431 (16)0.0295 (13)0.0022 (13)0.0004 (12)0.0071 (12)
O210.0364 (10)0.0407 (11)0.0321 (9)0.0063 (9)0.0052 (8)0.0003 (8)
C220.0254 (13)0.0262 (13)0.0298 (13)0.0028 (11)0.0013 (10)0.0007 (10)
C230.0261 (12)0.0271 (13)0.0313 (13)0.0013 (10)0.0047 (10)0.0018 (10)
C240.0260 (13)0.0280 (13)0.0355 (13)0.0009 (10)0.0003 (10)0.0021 (11)
C250.0244 (13)0.0282 (13)0.0418 (14)0.0023 (10)0.0003 (11)0.0054 (11)
C260.0280 (13)0.0387 (15)0.0345 (13)0.0014 (11)0.0053 (11)0.0063 (12)
C270.0310 (14)0.0329 (14)0.0291 (13)0.0028 (11)0.0027 (11)0.0015 (11)
O280.0308 (10)0.0385 (11)0.0426 (10)0.0064 (8)0.0030 (8)0.0125 (9)
C290.0268 (13)0.0472 (17)0.0411 (14)0.0013 (12)0.0016 (12)0.0156 (13)
C300.0433 (19)0.074 (3)0.058 (2)0.0110 (17)0.0045 (16)0.0294 (19)
O310.0294 (10)0.0447 (12)0.0479 (12)0.0124 (9)0.0021 (9)0.0050 (9)
C320.0360 (17)0.078 (3)0.0468 (18)0.0207 (17)0.0054 (14)0.0264 (17)
C340.110 (4)0.117 (4)0.180 (6)0.043 (4)0.041 (4)0.025 (4)
C350.097 (3)0.085 (3)0.190 (7)0.026 (3)0.057 (4)0.039 (4)
C360.135 (6)0.119 (6)0.186 (9)0.021 (6)0.078 (6)0.033 (6)
N370.175 (7)0.159 (7)0.175 (11)0.006 (8)0.064 (7)0.041 (7)
O380.213 (9)0.192 (9)0.236 (10)0.030 (9)0.026 (10)0.029 (9)
C330.108 (5)0.105 (5)0.162 (7)0.029 (5)0.049 (5)0.046 (5)
N1330.132 (7)0.102 (6)0.155 (8)0.016 (6)0.042 (7)0.039 (6)
Geometric parameters (Å, º) top
S1—O21.445 (2)C22—C271.377 (4)
S1—O31.439 (2)C23—C241.393 (4)
S1—C41.754 (3)C23—H2310.937
S1—C51.774 (3)C24—C251.406 (4)
C4—H410.953C24—O281.370 (3)
C4—H430.957C25—C261.379 (4)
C4—H420.962C25—O311.380 (3)
C5—C61.528 (3)C26—C271.389 (4)
C5—H520.966C26—H2610.919
C5—H510.978C27—H2710.944
C6—N71.475 (3)O28—C291.439 (3)
C6—C221.525 (4)C29—C301.503 (4)
C6—H610.966C29—H2920.961
N7—C81.392 (3)C29—H2910.984
N7—C111.393 (3)C30—H3020.964
C8—C91.485 (4)C30—H3010.960
C8—O121.225 (3)C30—H3030.962
C9—C101.386 (3)O31—C321.431 (4)
C9—C141.387 (4)C32—H3210.974
C10—C111.482 (4)C32—H3230.965
C10—C171.378 (4)C32—H3220.990
C11—O131.219 (3)C34—C351.425 (10)
C14—C151.397 (4)C34—H3410.991
C14—N181.401 (3)C34—C331.474 (10)
C15—C161.386 (4)C34—N1331.452 (10)
C15—H1510.922C35—C35i1.360 (14)
C16—C171.393 (4)C35—C361.378 (9)
C16—H1610.958C35—H3510.950
C17—H1710.942C36—N371.445 (9)
N18—C191.364 (3)C36—O381.263 (9)
N18—H1810.834N37—N37i1.24 (3)
C19—C201.508 (4)H331—C331.217
C19—O211.215 (3)H331—N1331.229
C20—H2010.942C33—N133i1.419 (14)
C20—H2030.938C33—C33i1.410 (14)
C20—H2020.947N133—N133i1.430 (14)
C22—C231.402 (4)
O2—S1—O3117.61 (12)C23—C22—C27119.3 (2)
O2—S1—C4108.26 (14)C22—C23—C24120.5 (2)
O3—S1—C4109.17 (14)C22—C23—H231119.5
O2—S1—C5108.81 (12)C24—C23—H231119.9
O3—S1—C5109.47 (12)C23—C24—C25119.2 (2)
C4—S1—C5102.45 (13)C23—C24—O28124.4 (2)
S1—C4—H41109.2C25—C24—O28116.4 (2)
S1—C4—H43105.4C24—C25—C26119.8 (2)
H41—C4—H43110.1C24—C25—O31115.5 (2)
S1—C4—H42110.1C26—C25—O31124.8 (2)
H41—C4—H42111.9C25—C26—C27120.5 (2)
H43—C4—H42109.9C25—C26—H261120.0
S1—C5—C6113.37 (17)C27—C26—H261119.4
S1—C5—H52105.6C26—C27—C22120.7 (3)
C6—C5—H52107.6C26—C27—H271120.5
S1—C5—H51107.0C22—C27—H271118.8
C6—C5—H51111.1C24—O28—C29116.7 (2)
H52—C5—H51112.2O28—C29—C30108.4 (2)
C5—C6—N7111.4 (2)O28—C29—H292108.0
C5—C6—C22111.3 (2)C30—C29—H292108.4
N7—C6—C22112.4 (2)O28—C29—H291111.2
C5—C6—H61107.6C30—C29—H291112.3
N7—C6—H61105.3H292—C29—H291108.3
C22—C6—H61108.4C29—C30—H302110.0
C6—N7—C8123.5 (2)C29—C30—H301109.9
C6—N7—C11125.2 (2)H302—C30—H301109.3
C8—N7—C11110.9 (2)C29—C30—H303106.0
N7—C8—C9106.6 (2)H302—C30—H303111.4
N7—C8—O12124.9 (2)H301—C30—H303110.2
C9—C8—O12128.6 (2)C25—O31—C32115.6 (2)
C8—C9—C10108.0 (2)O31—C32—H321106.9
C8—C9—C14130.0 (2)O31—C32—H323110.9
C10—C9—C14122.1 (2)H321—C32—H323109.0
C9—C10—C11107.7 (2)O31—C32—H322110.8
C9—C10—C17122.1 (2)H321—C32—H322108.4
C11—C10—C17130.1 (2)H323—C32—H322110.6
C10—C11—N7106.8 (2)C35—C34—H341120.5
C10—C11—O13128.6 (2)C35—C34—C33116.0 (8)
N7—C11—O13124.6 (2)H341—C34—C33123.5
C9—C14—C15116.3 (2)C35—C34—N133115.9 (8)
C9—C14—N18118.3 (2)H341—C34—N133123.7
C15—C14—N18125.4 (2)C33—C34—N1331.779 (13)
C14—C15—C16121.0 (3)C34—C35—C35i123.1 (5)
C14—C15—H151120.3C34—C35—C36119.7 (7)
C16—C15—H151118.7C35i—C35—C36117.1 (5)
C15—C16—C17122.5 (2)C34—C35—H351118.8
C15—C16—H161119.3C35i—C35—H351118.0
C17—C16—H161118.1C36—C35—H3511.1
C16—C17—C10116.0 (2)C35—C36—N37122.1 (11)
C16—C17—H171122.5C35—C36—O38119.4 (2)
C10—C17—H171121.5N37—C36—O38118.3 (11)
C14—N18—C19128.7 (2)C36—N37—N37i115.0 (10)
C14—N18—H181115.9C33—H331—N1332.3
C19—N18—H181115.4C34—C33—N133i119.9 (5)
N18—C19—C20113.9 (2)C34—C33—H331103.4
N18—C19—O21123.5 (2)N133i—C33—H331136.4
C20—C19—O21122.6 (2)C34—C33—C33i120.8 (5)
C19—C20—H201110.5N133i—C33—C33i2.01 (2)
C19—C20—H203110.8H331—C33—C33i135.7
H201—C20—H203108.0C34—N133—N133i120.7 (5)
C19—C20—H202111.4C34—N133—C33i121.7 (5)
H201—C20—H202108.5N133i—N133—C33i1.98 (2)
H203—C20—H202107.5C34—N133—H331104.0
C6—C22—C23121.9 (2)N133i—N133—H331134.0
C6—C22—C27118.8 (2)C33i—N133—H331133.5
Symmetry code: (i) y+1, x+1, z+1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N18—H181···O120.832.322.975 (5)136
C15—H151···O210.922.332.908 (5)120
C32—H321···O21ii0.972.543.484 (5)164
C23—H231···O13iii0.942.433.360 (5)176
C26—H261···O3iv0.922.453.348 (5)165
C27—H271···O2iv0.942.523.267 (5)136
C5—H52···O21iv0.972.503.438 (5)165
C5—H51···O13iii0.982.293.146 (5)146
C4—H43···O12v0.962.423.042 (5)123
C4—H42···O2iii0.962.543.386 (5)147
C35—H351···N370.951.722.471 (5)133
C35—H351···O380.951.512.281 (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, x1/2, z+1/4.
(apremilastniacin) top
Crystal data top
2(C22H24N2O7S)·C6H5NO2Dx = 1.415 Mg m3
Mr = 1044.09Cu Kα radiation, λ = 1.54184 Å
Tetragonal, P41212Cell parameters from 42937 reflections
a = 12.9268 (1) Åθ = 5–67°
c = 29.3204 (2) ŵ = 1.65 mm1
V = 4899.50 (8) Å3T = 120 K
Z = 4Block, colorless
F(000) = 21920.29 × 0.28 × 0.21 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4270 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.060
ω scansθmax = 67.5°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.44, Tmax = 0.71k = 1515
83935 measured reflectionsl = 3534
4406 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.036 Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.04P)2 + 4.32P] ,
where P = (max(Fo2,0) + 2Fc2)/3
wR(F2) = 0.093(Δ/σ)max = 0.003
S = 1.00Δρmax = 0.29 e Å3
4406 reflectionsΔρmin = 0.31 e Å3
353 parametersAbsolute structure: Flack (1983), 1809 Friedel-pairs
20 restraintsAbsolute structure parameter: 0.003 (19)
Primary atom site location: structure-invariant direct methods
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.59601 (5)0.83687 (4)0.464702 (19)0.0259
O20.55379 (14)0.92432 (13)0.44083 (6)0.0355
O30.68880 (13)0.79027 (14)0.44653 (6)0.0325
C40.6193 (2)0.8715 (2)0.52176 (9)0.0418
C50.49931 (18)0.73988 (18)0.47024 (7)0.0247
C60.45581 (18)0.70322 (18)0.42456 (7)0.0241
N70.53685 (15)0.65596 (14)0.39608 (6)0.0224
C80.56631 (17)0.69460 (17)0.35336 (7)0.0217
C90.65621 (18)0.63246 (17)0.33854 (8)0.0227
C100.67799 (19)0.55998 (18)0.37203 (7)0.0257
C110.60169 (19)0.57523 (18)0.40940 (8)0.0251
O120.52327 (13)0.76583 (12)0.33374 (5)0.0268
O130.59388 (14)0.52813 (13)0.44514 (5)0.0305
C140.71201 (18)0.63665 (18)0.29790 (8)0.0259
C150.7932 (2)0.5662 (2)0.29372 (9)0.0322
C160.8147 (2)0.4949 (2)0.32790 (10)0.0383
C170.7568 (2)0.4896 (2)0.36776 (9)0.0331
N180.68222 (15)0.70935 (15)0.26508 (6)0.0267
C190.72369 (19)0.72518 (19)0.22266 (8)0.0282
C200.6620 (2)0.7992 (2)0.19363 (8)0.0363
O210.80150 (14)0.68275 (14)0.20918 (6)0.0344
C220.36378 (18)0.63129 (18)0.43143 (8)0.0248
C230.34839 (18)0.57601 (19)0.47199 (8)0.0282
C240.26238 (19)0.5122 (2)0.47731 (9)0.0325
C250.19014 (19)0.50399 (19)0.44169 (10)0.0326
C260.20607 (19)0.55836 (19)0.40163 (9)0.0306
C270.29219 (19)0.62181 (18)0.39673 (8)0.0274
O280.24210 (14)0.45491 (16)0.51564 (7)0.0452
C290.3187 (2)0.4577 (3)0.55131 (10)0.0453
C300.2882 (2)0.3786 (3)0.58691 (13)0.0686
O310.10716 (14)0.44038 (15)0.44999 (7)0.0427
C320.0356 (2)0.4294 (3)0.41309 (10)0.0480
O400.5639 (6)0.3097 (5)0.3341 (2)0.09530.5000
O410.6329 (5)0.2656 (5)0.2657 (2)0.08940.5000
C420.5804 (6)0.3287 (6)0.2936 (3)0.06650.5000
C430.5451 (2)0.4269 (2)0.27201 (13)0.0722
C440.4688 (2)0.4788 (2)0.29429 (11)0.0687
C450.4153 (5)0.5564 (4)0.2718 (3)0.07070.5000
N460.4140 (5)0.5576 (5)0.2719 (3)0.11620.5000
H410.44350.76920.48800.0289*
H420.52890.68170.48690.0289*
H510.43320.76420.40810.0284*
H1710.70310.82080.16830.0553*
H1720.60320.76480.18230.0550*
H1730.63930.85990.21090.0548*
H1810.83480.56540.26820.0392*
H1910.87140.45050.32440.0459*
H2010.77070.44110.39000.0402*
H2210.39510.58480.49600.0336*
H2510.32530.53000.56270.0544*
H2520.38350.43670.53800.0545*
H2610.22400.39710.59940.0999*
H2620.33890.37770.61060.1006*
H2630.28530.31280.57230.1002*
H2910.06880.40020.38690.0732*
H2920.00250.49750.40590.0735*
H2930.01630.38130.42360.0724*
H3010.15840.55530.37840.0355*
H3110.30210.65960.37000.0326*
H3210.64680.81150.53800.0624*
H3220.66800.92710.52100.0624*
H3230.55610.89440.53520.0629*
H4310.57930.36920.28730.0871*0.5000
H4410.45220.46260.32500.0828*
H4510.35900.59050.28630.0806*0.5000
H4110.65190.20590.28270.1029*0.5000
H1820.62630.75330.27320.0322*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0292 (3)0.0257 (3)0.0227 (2)0.0070 (2)0.0011 (2)0.0030 (2)
O20.0390 (10)0.0263 (9)0.0413 (10)0.0058 (8)0.0027 (8)0.0025 (8)
O30.0281 (9)0.0383 (10)0.0312 (9)0.0046 (8)0.0039 (7)0.0007 (8)
C40.0451 (16)0.0495 (17)0.0310 (13)0.0084 (13)0.0013 (12)0.0150 (12)
C50.0275 (12)0.0268 (12)0.0198 (10)0.0060 (9)0.0006 (9)0.0016 (9)
C60.0289 (12)0.0231 (11)0.0202 (10)0.0009 (10)0.0032 (9)0.0029 (9)
N70.0285 (10)0.0209 (9)0.0177 (8)0.0001 (8)0.0043 (7)0.0015 (7)
C80.0255 (12)0.0215 (11)0.0182 (10)0.0042 (9)0.0050 (9)0.0007 (8)
C90.0250 (11)0.0199 (11)0.0231 (10)0.0025 (9)0.0068 (9)0.0010 (9)
C100.0291 (12)0.0245 (11)0.0235 (10)0.0035 (9)0.0074 (9)0.0036 (9)
C110.0308 (12)0.0229 (11)0.0218 (11)0.0014 (10)0.0074 (9)0.0012 (9)
O120.0307 (9)0.0264 (9)0.0234 (7)0.0049 (7)0.0026 (7)0.0063 (7)
O130.0416 (10)0.0278 (9)0.0222 (8)0.0004 (8)0.0048 (7)0.0069 (7)
C140.0265 (12)0.0257 (12)0.0255 (12)0.0025 (9)0.0040 (9)0.0034 (9)
C150.0295 (13)0.0325 (13)0.0347 (13)0.0032 (10)0.0032 (10)0.0076 (10)
C160.0325 (14)0.0358 (15)0.0467 (15)0.0116 (12)0.0022 (12)0.0120 (12)
C170.0357 (14)0.0299 (13)0.0336 (13)0.0049 (11)0.0050 (11)0.0111 (11)
N180.0261 (10)0.0293 (11)0.0246 (10)0.0053 (9)0.0004 (8)0.0070 (8)
C190.0310 (13)0.0296 (12)0.0240 (11)0.0026 (10)0.0023 (10)0.0022 (10)
C200.0386 (15)0.0447 (16)0.0255 (12)0.0050 (13)0.0015 (11)0.0107 (11)
O210.0342 (10)0.0415 (10)0.0275 (9)0.0072 (8)0.0049 (7)0.0027 (7)
C220.0269 (12)0.0225 (11)0.0250 (11)0.0018 (10)0.0035 (9)0.0004 (9)
C230.0260 (12)0.0286 (12)0.0301 (12)0.0044 (10)0.0097 (10)0.0079 (10)
C240.0280 (13)0.0274 (13)0.0420 (14)0.0034 (10)0.0054 (11)0.0103 (10)
C250.0234 (12)0.0250 (12)0.0493 (15)0.0019 (10)0.0070 (11)0.0013 (11)
C260.0283 (13)0.0290 (13)0.0344 (13)0.0023 (10)0.0096 (10)0.0046 (10)
C270.0295 (13)0.0267 (12)0.0261 (12)0.0040 (10)0.0042 (10)0.0003 (9)
O280.0279 (10)0.0492 (12)0.0585 (12)0.0108 (9)0.0115 (9)0.0310 (10)
C290.0244 (13)0.0617 (19)0.0499 (16)0.0032 (13)0.0048 (12)0.0328 (15)
C300.0332 (17)0.099 (3)0.073 (2)0.0049 (17)0.0027 (16)0.057 (2)
O310.0281 (10)0.0394 (11)0.0607 (12)0.0113 (8)0.0133 (9)0.0078 (9)
C320.0269 (14)0.068 (2)0.0488 (16)0.0167 (14)0.0055 (12)0.0243 (15)
O400.123 (6)0.077 (4)0.085 (4)0.000 (4)0.012 (4)0.001 (3)
O410.108 (5)0.076 (4)0.085 (4)0.033 (3)0.029 (4)0.009 (3)
C420.079 (5)0.057 (4)0.064 (5)0.005 (4)0.014 (4)0.014 (4)
C430.063 (2)0.070 (2)0.083 (2)0.0100 (19)0.010 (2)0.018 (2)
C440.054 (2)0.074 (3)0.078 (3)0.0051 (19)0.0023 (19)0.012 (2)
C450.054 (3)0.070 (4)0.088 (4)0.006 (3)0.017 (3)0.030 (3)
N460.105 (6)0.120 (6)0.124 (6)0.017 (6)0.000 (6)0.023 (6)
Geometric parameters (Å, º) top
S1—O21.4373 (19)C22—C271.381 (3)
S1—O31.4441 (18)C23—C241.393 (3)
S1—C41.758 (3)C23—H2210.935
S1—C51.778 (2)C24—C251.405 (4)
C4—H3210.977C24—O281.371 (3)
C4—H3220.955C25—C261.384 (4)
C4—H3230.955C25—O311.373 (3)
C5—C61.528 (3)C26—C271.390 (4)
C5—H410.967C26—H3010.919
C5—H420.974C27—H3110.932
C6—N71.472 (3)O28—C291.440 (3)
C6—C221.523 (3)C29—C301.513 (4)
C6—H510.969C29—H2510.996
N7—C81.401 (3)C29—H2520.964
N7—C111.394 (3)C30—H2610.938
C8—C91.478 (3)C30—H2620.955
C8—O121.220 (3)C30—H2630.955
C9—C101.386 (3)O31—C321.431 (3)
C9—C141.394 (3)C32—H2910.957
C10—C111.487 (3)C32—H2921.001
C10—C171.371 (3)C32—H2930.964
C11—O131.216 (3)O40—C421.230 (10)
C14—C151.395 (3)O41—C421.340 (9)
C14—N181.399 (3)O41—H4110.950
C15—C161.390 (4)C42—C431.490 (9)
C15—H1810.922C42—H4310.555
C16—C171.389 (4)C43—C43i1.389 (8)
C16—H1910.937C43—C441.359 (5)
C17—H2010.923C43—H4310.976
N18—C191.370 (3)C44—C451.386 (8)
N18—H1820.950C44—N461.405 (8)
C19—C201.509 (3)C44—H4410.950
C19—O211.212 (3)C45—N46i1.382 (9)
C20—H1710.956C45—C45i1.380 (17)
C20—H1720.940C45—H4510.950
C20—H1730.979N46—N46i1.384 (19)
C22—C231.402 (3)N46—H4510.929
O2—S1—O3117.63 (11)C22—C23—H221119.1
O2—S1—C4109.18 (13)C24—C23—H221120.2
O3—S1—C4108.36 (13)C23—C24—C25119.5 (2)
O2—S1—C5109.40 (11)C23—C24—O28124.3 (2)
O3—S1—C5108.88 (11)C25—C24—O28116.2 (2)
C4—S1—C5102.30 (12)C24—C25—C26119.6 (2)
S1—C4—H321108.9C24—C25—O31115.6 (2)
S1—C4—H322106.4C26—C25—O31124.8 (2)
H321—C4—H322111.7C25—C26—C27120.4 (2)
S1—C4—H323109.0C25—C26—H301120.4
H321—C4—H323110.9C27—C26—H301119.1
H322—C4—H323109.8C26—C27—C22120.8 (2)
S1—C5—C6113.42 (15)C26—C27—H311120.4
S1—C5—H41107.3C22—C27—H311118.7
C6—C5—H41108.6C24—O28—C29116.75 (19)
S1—C5—H42108.3O28—C29—C30107.8 (2)
C6—C5—H42110.1O28—C29—H251109.0
H41—C5—H42109.0C30—C29—H251115.1
C5—C6—N7111.34 (19)O28—C29—H252107.2
C5—C6—C22111.15 (18)C30—C29—H252108.4
N7—C6—C22112.18 (18)H251—C29—H252109.0
C5—C6—H51107.2C29—C30—H261109.1
N7—C6—H51105.7C29—C30—H262109.4
C22—C6—H51109.0H261—C30—H262109.1
C6—N7—C8123.53 (18)C29—C30—H263107.6
C6—N7—C11125.42 (18)H261—C30—H263111.5
C8—N7—C11110.71 (19)H262—C30—H263110.1
N7—C8—C9106.43 (19)C25—O31—C32115.5 (2)
N7—C8—O12124.5 (2)O31—C32—H291110.8
C9—C8—O12129.1 (2)O31—C32—H292110.3
C8—C9—C10108.6 (2)H291—C32—H292111.7
C8—C9—C14129.6 (2)O31—C32—H293105.8
C10—C9—C14121.8 (2)H291—C32—H293108.4
C9—C10—C11107.3 (2)H292—C32—H293109.7
C9—C10—C17122.3 (2)C42—O41—H411107.8
C11—C10—C17130.4 (2)O41—C42—O40123.8 (8)
C10—C11—N7106.96 (18)O41—C42—C43114.5 (6)
C10—C11—O13128.6 (2)O40—C42—C43121.8 (7)
N7—C11—O13124.5 (2)O41—C42—H431112.5
C9—C14—C15116.1 (2)O40—C42—H431120.4
C9—C14—N18118.1 (2)C43—C42—H43117.8
C15—C14—N18125.8 (2)C42—C43—C43i122.5 (4)
C14—C15—C16121.3 (2)C42—C43—C44116.0 (4)
C14—C15—H181121.2C43i—C43—C44120.5 (2)
C16—C15—H181117.5C42—C43—H43110.0
C15—C16—C17122.1 (2)C43i—C43—H431120.5
C15—C16—H191119.0C44—C43—H431119.0
C17—C16—H191118.9C43—C44—C45119.4 (4)
C16—C17—C10116.4 (2)C43—C44—N46120.0 (4)
C16—C17—H201121.5C45—C44—N460.5 (7)
C10—C17—H201122.1C43—C44—H441120.7
C14—N18—C19128.1 (2)C45—C44—H441119.8
C14—N18—H182116.0N46—C44—H441119.3
C19—N18—H182115.9C44—C45—N46i121.0 (9)
N18—C19—C20113.6 (2)C44—C45—C45i120.0 (4)
N18—C19—O21123.6 (2)N46i—C45—C45i0.9 (6)
C20—C19—O21122.8 (2)C44—C45—H451120.4
C19—C20—H171109.3N46i—C45—H451118.6
C19—C20—H172109.0C45i—C45—H451119.6
H171—C20—H172108.1C44—N46—N46i119.5 (4)
C19—C20—H173112.0C44—N46—C45i118.5 (9)
H171—C20—H173109.6N46i—N46—C45i0.9 (6)
H172—C20—H173108.7C44—N46—H451120.4
C6—C22—C23122.3 (2)N46i—N46—H451120.1
C6—C22—C27118.7 (2)C45i—N46—H451121.1
C23—C22—C27119.0 (2)C43—H431—C42152.2
C22—C23—C24120.7 (2)C45—H451—N460.6
Symmetry code: (i) y+1, x+1, z+1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H41···O21ii0.972.483.438 (4)170
C5—H42···O130.972.483.087 (4)120
C5—H42···O13iii0.972.293.140 (4)145
C23—H221···O13iii0.942.443.370 (4)174
C26—H301···O2ii0.922.453.358 (4)168
C27—H311···O3ii0.932.523.249 (4)135
C4—H321···O3iii0.982.483.365 (4)150
C4—H322···O12iv0.962.383.059 (4)128
C43—H431···O400.981.582.380 (4)135
C43—H431···O410.981.642.381 (4)130
O41—H411···O31v0.952.042.865 (4)144
N18—H182···O120.952.222.968 (4)134
Symmetry codes: (ii) x1/2, 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) top
Crystal data top
C26H30.50N2O7SDx = 1.377 Mg m3
Mr = 515.10Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 65234 reflections
a = 13.1850 (1) Åθ = 4–68°
c = 28.5930 (1) ŵ = 1.58 mm1
V = 4970.73 (8) Å3T = 120 K
Z = 8Plate, colorless
F(000) = 21800.28 × 0.23 × 0.11 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4440 reflections with I > 2.0σ(I)
Focussing mirrors monochromatorRint = 0.031
ω scansθmax = 67.7°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro (Rigaku Oxford Diffraction, 2017)
h = 1515
Tmin = 0.46, Tmax = 0.84k = 1515
97817 measured reflectionsl = 3434
4498 independent reflections
Refinement top
Refinement on F2H-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[F2 > 2σ(F2)] = 0.027(Δ/σ)max = 0.001
wR(F2) = 0.060Δρmax = 0.32 e Å3
S = 0.93Δρmin = 0.78 e Å3
4498 reflectionsExtinction correction: Larson (1970), Equation 22
333 parametersExtinction coefficient: 46 (3)
46 restraintsAbsolute structure: Parsons, Flack & Wagner (2013), 1844 Friedel Pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.001 (2)
Hydrogen site location: difference Fourier map
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.41595 (4)0.17294 (4)0.464742 (16)0.0220
O20.32619 (11)0.21876 (11)0.44496 (5)0.0281
O30.45695 (11)0.08485 (11)0.44171 (5)0.0318
C40.39237 (17)0.14366 (18)0.52390 (7)0.0337
C50.51135 (14)0.26710 (14)0.46951 (6)0.0209
C60.55298 (14)0.30413 (14)0.42271 (6)0.0197
N70.47209 (12)0.35062 (12)0.39377 (5)0.0191
C80.40838 (14)0.42905 (14)0.40826 (6)0.0195
C90.33061 (14)0.44164 (14)0.37099 (6)0.0195
C100.35046 (14)0.36987 (13)0.33659 (6)0.0181
C110.44020 (14)0.31037 (14)0.35103 (6)0.0183
O120.41718 (11)0.47532 (10)0.44476 (4)0.0248
O130.48095 (10)0.24026 (10)0.33065 (4)0.0233
C140.25166 (15)0.50996 (15)0.36725 (7)0.0234
C150.19221 (15)0.50244 (15)0.32708 (7)0.0252
C160.21127 (14)0.43152 (14)0.29206 (7)0.0227
C170.29236 (14)0.36289 (14)0.29639 (6)0.0191
N180.31978 (12)0.28975 (12)0.26321 (5)0.0210
C190.27730 (15)0.27130 (15)0.22021 (6)0.0228
C200.33594 (16)0.19658 (16)0.19115 (7)0.0283
O210.19965 (11)0.31228 (11)0.20653 (4)0.0277
C220.64330 (14)0.37427 (14)0.42984 (6)0.0203
C230.65628 (14)0.42961 (14)0.47124 (6)0.0212
C240.74127 (15)0.49010 (15)0.47779 (6)0.0219
C250.81534 (14)0.49611 (15)0.44246 (7)0.0235
C260.80205 (15)0.44154 (16)0.40148 (7)0.0252
C270.71625 (15)0.38078 (15)0.39541 (7)0.0239
O280.75978 (11)0.54603 (11)0.51735 (5)0.0271
C290.68238 (16)0.54356 (17)0.55291 (7)0.0284
C300.7125 (2)0.6155 (2)0.59124 (9)0.0474
O310.89741 (11)0.55618 (12)0.45196 (5)0.0319
C320.96898 (17)0.5685 (2)0.41495 (8)0.0393
C340.3908 (2)0.6092 (2)0.25000.0850
C350.4557 (2)0.5997 (2)0.28672 (11)0.0652
C360.5292 (2)0.5258 (2)0.28705 (9)0.0515
C370.53975 (17)0.46025 (17)0.25000.0445
C380.6194 (2)0.3806 (2)0.25000.1108
H430.45730.12880.53870.0507*
H420.35790.20170.53880.0504*
H520.56650.23800.48710.0244*
H510.48320.32380.48720.0237*
H610.57630.24320.40500.0220*
H1410.23860.56060.39110.0266*
H1510.13780.54780.32250.0296*
H1610.16870.43020.26500.0267*
H2010.29540.17320.16510.0425*
H2020.39730.22920.17910.0431*
H2030.35580.13800.20940.0432*
H2310.60650.42590.49430.0245*
H2610.85080.44470.37700.0294*
H2710.70750.34170.36680.0277*
H2910.67620.47330.56550.0340*
H2920.61630.56440.53950.0349*
H3030.66260.61440.61630.0717*
H3020.78070.60110.60320.0704*
H3010.71690.68640.57760.0701*
H3231.02390.61440.42650.0576*
H3220.99830.50370.40520.0586*
H3210.93590.60120.38780.0570*
H1810.37200.25530.27040.0230*
H410.34920.08540.52440.0493*
C330.3106 (3)0.6894 (3)0.25000.1633
H3510.44970.64860.31250.0827*
H3610.57340.52150.31280.0655*
H3810.63570.33990.22010.1638*0.5000
H3820.69400.40030.25740.1643*0.5000
H3830.61640.32050.27320.1630*0.5000
H3310.27230.68500.22190.1903*
H3320.34160.75430.25200.1903*
H3330.26700.67980.27610.1903*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0216 (2)0.0229 (2)0.0215 (2)0.00309 (18)0.00278 (19)0.00168 (18)
O20.0228 (7)0.0350 (8)0.0264 (7)0.0023 (6)0.0043 (6)0.0042 (6)
O30.0335 (8)0.0260 (7)0.0359 (8)0.0025 (6)0.0031 (7)0.0064 (7)
C40.0342 (12)0.0398 (13)0.0270 (11)0.0060 (10)0.0018 (9)0.0094 (9)
C50.0221 (9)0.0215 (10)0.0189 (9)0.0018 (7)0.0026 (7)0.0013 (7)
C60.0195 (9)0.0222 (9)0.0174 (8)0.0034 (7)0.0000 (7)0.0012 (7)
N70.0205 (8)0.0209 (8)0.0158 (7)0.0012 (6)0.0003 (6)0.0018 (6)
C80.0213 (9)0.0183 (9)0.0188 (9)0.0023 (7)0.0044 (8)0.0006 (7)
C90.0213 (9)0.0187 (9)0.0186 (8)0.0032 (7)0.0034 (7)0.0001 (7)
C100.0181 (9)0.0172 (9)0.0189 (9)0.0029 (7)0.0027 (7)0.0016 (7)
C110.0188 (9)0.0195 (9)0.0165 (8)0.0024 (7)0.0029 (7)0.0003 (7)
O120.0304 (7)0.0245 (7)0.0196 (6)0.0002 (6)0.0012 (6)0.0061 (6)
O130.0250 (7)0.0243 (7)0.0206 (6)0.0036 (5)0.0003 (5)0.0056 (6)
C140.0249 (10)0.0223 (10)0.0230 (9)0.0003 (8)0.0044 (8)0.0017 (8)
C150.0225 (10)0.0242 (10)0.0289 (10)0.0035 (8)0.0025 (8)0.0007 (8)
C160.0214 (9)0.0244 (10)0.0224 (9)0.0004 (8)0.0011 (8)0.0009 (8)
C170.0213 (9)0.0191 (9)0.0170 (9)0.0028 (7)0.0022 (7)0.0009 (7)
N180.0218 (8)0.0226 (8)0.0185 (7)0.0018 (7)0.0007 (6)0.0034 (6)
C190.0261 (10)0.0243 (10)0.0180 (9)0.0062 (8)0.0018 (8)0.0003 (8)
C200.0324 (11)0.0312 (11)0.0213 (9)0.0007 (9)0.0018 (9)0.0056 (8)
O210.0276 (8)0.0353 (8)0.0203 (7)0.0014 (6)0.0049 (6)0.0017 (6)
C220.0198 (9)0.0212 (9)0.0200 (9)0.0025 (7)0.0004 (7)0.0013 (7)
C230.0212 (9)0.0221 (10)0.0202 (9)0.0001 (7)0.0027 (7)0.0012 (7)
C240.0227 (10)0.0224 (10)0.0205 (9)0.0013 (7)0.0013 (8)0.0003 (7)
C250.0183 (9)0.0252 (10)0.0269 (10)0.0017 (7)0.0013 (8)0.0041 (8)
C260.0223 (10)0.0306 (11)0.0227 (9)0.0016 (8)0.0029 (8)0.0025 (8)
C270.0236 (10)0.0295 (10)0.0188 (9)0.0030 (8)0.0007 (7)0.0000 (8)
O280.0265 (7)0.0293 (8)0.0255 (7)0.0071 (6)0.0019 (6)0.0075 (6)
C290.0244 (10)0.0349 (11)0.0260 (10)0.0006 (9)0.0012 (8)0.0088 (9)
C300.0453 (15)0.0599 (17)0.0370 (13)0.0101 (13)0.0052 (11)0.0229 (12)
O310.0234 (7)0.0403 (9)0.0320 (8)0.0113 (6)0.0020 (6)0.0016 (7)
C320.0242 (11)0.0619 (16)0.0318 (11)0.0134 (11)0.0017 (9)0.0165 (11)
C340.0468 (15)0.0468 (15)0.161 (4)0.0130 (19)0.053 (2)0.053 (2)
C350.079 (2)0.0336 (14)0.082 (2)0.0176 (14)0.0505 (17)0.0126 (14)
C360.0479 (14)0.0625 (16)0.0443 (13)0.0272 (13)0.0059 (12)0.0104 (13)
C370.0325 (10)0.0325 (10)0.068 (2)0.0063 (14)0.0238 (12)0.0238 (12)
C380.076 (2)0.076 (2)0.181 (5)0.049 (3)0.083 (3)0.083 (3)
C330.088 (3)0.088 (3)0.314 (8)0.049 (3)0.105 (4)0.105 (4)
Geometric parameters (Å, º) top
S1—O21.4442 (14)C23—H2310.932
S1—O31.4404 (15)C24—C251.407 (3)
S1—C41.763 (2)C24—O281.372 (2)
S1—C51.7726 (18)C25—C261.386 (3)
C4—H430.975C25—O311.368 (2)
C4—H420.987C26—C271.397 (3)
C4—H410.956C26—H2610.952
C5—C61.527 (2)C27—H2710.973
C5—H520.964O28—C291.441 (2)
C5—H510.975C29—C301.503 (3)
C6—N71.483 (2)C29—H2910.997
C6—C221.521 (3)C29—H2920.991
C6—H610.998C30—H3030.973
N7—C81.395 (2)C30—H3020.980
N7—C111.397 (2)C30—H3011.013
C8—C91.488 (3)O31—C321.427 (3)
C8—O121.214 (2)C32—H3230.999
C9—C101.390 (3)C32—H3220.979
C9—C141.381 (3)C32—H3210.990
C10—C111.478 (2)C34—C35i1.360 (4)
C10—C171.385 (3)C34—C351.360 (4)
C11—O131.218 (2)C34—C331.496 (6)
C14—C151.394 (3)C35—C361.374 (4)
C14—H1410.970C35—H3510.982
C15—C161.393 (3)C36—C371.375 (3)
C15—H1510.943C36—H3610.940
C16—C171.406 (3)C37—C381.485 (5)
C16—H1610.956C38—H382i1.039
C17—N181.400 (2)C38—H383i1.035
N18—C191.373 (2)C38—H381i1.032
N18—H1810.850C38—H3811.032
C19—C201.503 (3)C38—H3821.039
C19—O211.222 (2)C38—H3831.035
C20—H2010.967C33—H333i0.950
C20—H2020.978C33—H332i0.950
C20—H2030.969C33—H331i0.950
C22—C231.401 (3)C33—H3310.950
C22—C271.379 (3)C33—H3320.950
C23—C241.388 (3)C33—H3330.950
O2—S1—O3117.76 (9)C26—C27—C22120.78 (18)
O2—S1—C4108.84 (10)C26—C27—H271120.3
O3—S1—C4109.17 (11)C22—C27—H271118.9
O2—S1—C5108.58 (9)C24—O28—C29116.34 (15)
O3—S1—C5109.49 (9)O28—C29—C30108.25 (17)
C4—S1—C5101.81 (9)O28—C29—H291109.4
S1—C4—H43107.8C30—C29—H291110.2
S1—C4—H42109.0O28—C29—H292110.0
H43—C4—H42111.9C30—C29—H292109.9
S1—C4—H41107.2H291—C29—H292109.0
H43—C4—H41110.8C29—C30—H303110.5
H42—C4—H41110.0C29—C30—H302111.9
S1—C5—C6114.31 (13)H303—C30—H302111.1
S1—C5—H52107.3C29—C30—H301108.5
C6—C5—H52108.2H303—C30—H301109.6
S1—C5—H51107.9H302—C30—H301105.1
C6—C5—H51110.3C25—O31—C32116.23 (17)
H52—C5—H51108.7O31—C32—H323107.7
C5—C6—N7111.28 (15)O31—C32—H322111.9
C5—C6—C22111.01 (15)H323—C32—H322109.7
N7—C6—C22112.74 (15)O31—C32—H321109.9
C5—C6—H61107.4H323—C32—H321108.4
N7—C6—H61105.7H322—C32—H321109.2
C22—C6—H61108.4C35i—C34—C35118.8 (4)
C6—N7—C8125.01 (14)C35i—C34—C33120.62 (18)
C6—N7—C11123.22 (15)C35—C34—C33120.62 (18)
C8—N7—C11111.10 (15)C34—C35—C36120.9 (3)
N7—C8—C9106.55 (14)C34—C35—H351117.9
N7—C8—O12124.75 (18)C36—C35—H351121.2
C9—C8—O12128.70 (18)C35—C36—C37120.8 (2)
C8—C9—C10107.52 (16)C35—C36—H361119.1
C8—C9—C14130.37 (17)C37—C36—H361120.1
C10—C9—C14122.10 (18)C36i—C37—C36117.8 (3)
C9—C10—C11108.32 (16)C36i—C37—C38121.11 (16)
C9—C10—C17121.91 (17)C36—C37—C38121.11 (16)
C11—C10—C17129.75 (17)H382i—C38—C37119.5
C10—C11—N7106.48 (15)H382i—C38—H383i95.6
C10—C11—O13128.48 (17)C37—C38—H383i121.0
N7—C11—O13125.04 (17)H382i—C38—H381i95.8
C9—C14—C15116.18 (18)C37—C38—H381i121.0
C9—C14—H141121.9H383i—C38—H381i98.1
C15—C14—H141121.9H382i—C38—H38152.5
C14—C15—C16122.59 (18)C37—C38—H381121.0
C14—C15—H151119.8H383i—C38—H38147.8
C16—C15—H151117.6H381i—C38—H381118.1
C15—C16—C17120.40 (18)H382i—C38—H382121.0
C15—C16—H161119.2C37—C38—H382119.5
C17—C16—H161120.4H383i—C38—H38252.8
C16—C17—C10116.81 (17)H381i—C38—H38252.5
C16—C17—N18125.45 (17)H381—C38—H38295.8
C10—C17—N18117.73 (17)H382i—C38—H38352.8
C17—N18—C19128.57 (17)C37—C38—H383121.0
C17—N18—H181114.4H383i—C38—H383118.1
C19—N18—H181116.9H381i—C38—H38347.8
N18—C19—C20113.67 (17)H381—C38—H38398.1
N18—C19—O21123.38 (18)H382—C38—H38395.6
C20—C19—O21122.95 (17)C34—C33—H333i109.5
C19—C20—H201110.5C34—C33—H332i109.5
C19—C20—H202109.3H333i—C33—H332i109.5
H201—C20—H202109.0C34—C33—H331i109.5
C19—C20—H203111.3H333i—C33—H331i109.5
H201—C20—H203108.1H332i—C33—H331i109.5
H202—C20—H203108.5C34—C33—H331109.5
C6—C22—C23121.69 (16)H333i—C33—H33156.2
C6—C22—C27119.22 (17)H332i—C33—H33156.2
C23—C22—C27119.05 (18)H331i—C33—H331141.1
C22—C23—C24120.79 (17)C34—C33—H332109.5
C22—C23—H231119.0H333i—C33—H33256.3
C24—C23—H231120.2H332i—C33—H332141.1
C23—C24—C25119.72 (17)H331i—C33—H33256.2
C23—C24—O28124.30 (17)H331—C33—H332109.5
C25—C24—O28115.98 (17)C34—C33—H333109.5
C24—C25—C26119.33 (17)H333i—C33—H333141.1
C24—C25—O31116.04 (17)H332i—C33—H33356.3
C26—C25—O31124.63 (18)H331i—C33—H33356.2
C25—C26—C27120.33 (18)H331—C33—H333109.5
C25—C26—H261120.9H332—C33—H333109.5
C27—C26—H261118.7
Symmetry code: (i) y+1, x+1, z+1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H42···O2ii0.992.503.439 (3)158
C5—H52···O21iii0.962.473.425 (3)169
C5—H51···O12ii0.982.303.186 (3)150
C23—H231···O12ii0.932.463.390 (3)180
C26—H261···O3iii0.952.443.375 (3)166
C27—H271···O2iii0.972.493.240 (3)134
C32—H323···O21iv1.002.583.566 (3)168
N18—H181···O130.852.252.943 (3)139
C4—H41···O13v0.962.423.208 (3)139
C38—H381···O2vi1.032.553.410 (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, x1/2, z+1/4; (vi) y+1/2, x+1/2, z1/4.
(apremilastsalycilic) top
Crystal data top
2(C22H24N2O7S)·C7H5O3Dx = 1.436 Mg m3
Mr = 1058.13Cu Kα radiation, λ = 1.54180 Å
Tetragonal, P41212Cell parameters from 72094 reflections
a = 12.9133 (1) Åθ = 3–68°
c = 29.3418 (1) ŵ = 1.67 mm1
V = 4892.84 (8) Å3T = 120 K
Z = 4Block, colorless
F(000) = 22200.68 × 0.39 × 0.36 mm
Data collection top
Oxford Diffraction SuperNova
diffractometer
4398 reflections with I > 2.0σ(I)
Graphite monochromatorRint = 0.027
ω scansθmax = 67.6°, θmin = 3.7°
Absorption correction: multi-scan
CrysAlisPro, (Agilent, 2011)
h = 1515
Tmin = 0.39, Tmax = 0.55k = 1515
93647 measured reflectionsl = 3534
4419 independent reflections
Refinement top
Refinement on F2H-atom parameters constrained
Least-squares matrix: full Method = Modified Sheldrick w = 1/[σ2(F2) + ( 0.03P)2 + 2.76P] ,
where P = (max(Fo2,0) + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.030(Δ/σ)max = 0.001
wR(F2) = 0.076Δρmax = 0.44 e Å3
S = 1.09Δρmin = 0.40 e Å3
4419 reflectionsExtinction correction: Larson (1970), Equation 22
354 parametersExtinction coefficient: 63 (8)
1 restraintAbsolute structure: Flack (1983), 1814 Friedel-pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.028 (15)
Hydrogen site location: difference Fourier map
Special details top

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 (Å2) top
xyzUiso*/UeqOcc. (<1)
S10.59471 (4)0.83550 (4)0.465138 (15)0.0242
O20.55171 (11)0.92326 (11)0.44146 (5)0.0340
O30.68726 (11)0.78879 (11)0.44645 (5)0.0310
C40.62007 (18)0.87021 (18)0.52192 (7)0.0389
C50.49789 (14)0.73890 (14)0.47098 (6)0.0224
C60.45306 (14)0.70281 (14)0.42521 (6)0.0213
N70.53400 (12)0.65588 (12)0.39636 (5)0.0207
C80.56265 (14)0.69524 (14)0.35381 (6)0.0204
C90.65200 (14)0.63294 (14)0.33836 (6)0.0216
C100.67405 (15)0.55974 (15)0.37176 (6)0.0250
C110.59820 (15)0.57410 (14)0.40918 (6)0.0236
O120.51982 (10)0.76676 (10)0.33449 (4)0.0253
O130.59024 (11)0.52582 (10)0.44459 (4)0.0289
C140.70797 (15)0.63807 (14)0.29797 (6)0.0235
C150.78966 (16)0.56738 (16)0.29312 (7)0.0307
C160.81141 (17)0.49541 (17)0.32723 (8)0.0369
C170.75325 (16)0.48928 (17)0.36721 (7)0.0331
N180.67843 (12)0.71109 (12)0.26532 (5)0.0244
C190.71945 (15)0.72760 (15)0.22300 (6)0.0264
C200.65841 (17)0.80243 (17)0.19426 (7)0.0342
O210.79725 (11)0.68414 (11)0.20920 (5)0.0329
C220.36090 (14)0.63116 (14)0.43198 (6)0.0226
C230.34596 (14)0.57445 (15)0.47212 (6)0.0259
C240.25982 (15)0.51068 (15)0.47698 (7)0.0295
C250.18764 (15)0.50373 (15)0.44125 (7)0.0291
C260.20275 (15)0.55945 (15)0.40171 (7)0.0274
C270.28941 (15)0.62329 (15)0.39718 (6)0.0255
O280.23942 (11)0.45088 (13)0.51442 (5)0.0420
C290.31609 (16)0.45051 (19)0.55017 (7)0.0385
C300.28629 (19)0.3685 (2)0.58428 (10)0.0579
O310.10442 (11)0.43955 (11)0.44928 (5)0.0371
C320.03223 (16)0.4294 (2)0.41256 (8)0.0408
O330.6391 (3)0.2618 (3)0.26068 (13)0.05340.5000
O340.5646 (3)0.3009 (3)0.32644 (13)0.05760.5000
C350.5850 (4)0.3231 (4)0.28769 (17)0.04390.5000
C360.5500 (2)0.4212 (2)0.27206 (13)0.0672
C370.4725 (2)0.4762 (2)0.29097 (11)0.0682
O380.4409 (3)0.4530 (3)0.33436 (11)0.06190.5000
C390.4187 (2)0.5552 (2)0.27152 (11)0.0725
H510.44280.76880.48980.0270*
H520.53070.68090.48770.0269*
H610.43070.76250.40790.0241*
H1510.83100.57010.26700.0357*
H1610.86930.45010.32260.0436*
H1710.76650.43900.38890.0403*
H2030.70010.82460.16910.0507*
H2010.63710.86230.21260.0508*
H2020.59660.76790.18260.0517*
H2310.39510.58090.49670.0306*
H2610.15660.55550.37780.0326*
H2710.29970.66200.37000.0300*
H2920.32050.51950.56520.0452*
H2910.38180.43350.53570.0450*
H3010.34120.36120.60670.0866*
H3020.22360.38800.60000.0867*
H3030.27820.30510.56800.0868*
H3220.02060.38020.42310.0598*
H3230.00080.49970.40520.0615*
H3210.06600.40030.38620.0605*
H3910.36320.59040.28730.0864*
H1810.62820.74940.27320.0286*
H410.64640.80920.53820.0575*
H430.67240.92270.52050.0574*
H420.55880.89680.53480.0575*
H3310.65590.20210.26920.0803*0.5000
H3610.57340.35560.28250.0807*0.5000
H3710.45050.46010.32110.0835*0.5000
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0265 (2)0.0249 (2)0.0213 (2)0.00683 (18)0.00231 (18)0.00325 (18)
O20.0377 (8)0.0261 (7)0.0381 (8)0.0055 (6)0.0026 (6)0.0039 (6)
O30.0260 (7)0.0381 (8)0.0290 (7)0.0046 (6)0.0059 (6)0.0031 (6)
C40.0425 (13)0.0452 (13)0.0291 (10)0.0099 (10)0.0007 (9)0.0148 (9)
C50.0242 (9)0.0241 (9)0.0189 (8)0.0059 (7)0.0022 (7)0.0012 (7)
C60.0248 (9)0.0209 (9)0.0184 (8)0.0005 (7)0.0014 (7)0.0004 (7)
N70.0252 (8)0.0203 (7)0.0166 (7)0.0008 (6)0.0026 (6)0.0016 (6)
C80.0229 (9)0.0204 (9)0.0177 (8)0.0038 (7)0.0031 (7)0.0000 (7)
C90.0222 (9)0.0198 (9)0.0227 (8)0.0019 (7)0.0039 (7)0.0002 (7)
C100.0271 (10)0.0231 (9)0.0247 (9)0.0008 (8)0.0038 (8)0.0040 (7)
C110.0279 (9)0.0211 (9)0.0219 (9)0.0010 (8)0.0060 (8)0.0015 (7)
O120.0277 (7)0.0262 (7)0.0219 (6)0.0036 (5)0.0019 (5)0.0055 (5)
O130.0371 (8)0.0264 (7)0.0232 (7)0.0003 (6)0.0035 (6)0.0065 (6)
C140.0249 (9)0.0223 (9)0.0233 (9)0.0019 (7)0.0028 (7)0.0018 (7)
C150.0292 (10)0.0304 (11)0.0326 (10)0.0041 (8)0.0050 (8)0.0062 (8)
C160.0319 (11)0.0334 (11)0.0454 (12)0.0126 (9)0.0072 (10)0.0115 (10)
C170.0331 (11)0.0297 (11)0.0365 (11)0.0077 (9)0.0014 (9)0.0115 (9)
N180.0241 (8)0.0260 (8)0.0231 (8)0.0048 (6)0.0006 (6)0.0037 (6)
C190.0288 (10)0.0271 (10)0.0232 (9)0.0027 (8)0.0013 (8)0.0003 (8)
C200.0362 (11)0.0410 (12)0.0253 (10)0.0035 (10)0.0002 (9)0.0090 (9)
O210.0333 (8)0.0391 (8)0.0263 (7)0.0075 (6)0.0059 (6)0.0012 (6)
C220.0245 (9)0.0204 (9)0.0228 (9)0.0005 (7)0.0028 (7)0.0015 (7)
C230.0240 (9)0.0262 (10)0.0276 (9)0.0031 (8)0.0099 (8)0.0047 (8)
C240.0273 (10)0.0253 (10)0.0358 (10)0.0032 (7)0.0076 (8)0.0093 (8)
C250.0222 (10)0.0217 (9)0.0433 (11)0.0028 (8)0.0074 (9)0.0006 (8)
C260.0263 (10)0.0270 (10)0.0288 (9)0.0030 (8)0.0090 (8)0.0050 (8)
C270.0266 (10)0.0263 (10)0.0236 (9)0.0034 (7)0.0041 (8)0.0009 (7)
O280.0282 (8)0.0469 (9)0.0510 (9)0.0154 (7)0.0157 (7)0.0284 (8)
C290.0228 (10)0.0530 (13)0.0398 (11)0.0066 (9)0.0079 (9)0.0245 (11)
C300.0334 (13)0.077 (2)0.0636 (16)0.0135 (12)0.0120 (12)0.0453 (15)
O310.0260 (7)0.0358 (8)0.0494 (9)0.0112 (6)0.0133 (7)0.0061 (7)
C320.0229 (10)0.0621 (16)0.0376 (12)0.0114 (10)0.0008 (9)0.0190 (11)
O330.051 (2)0.0397 (19)0.070 (2)0.0168 (16)0.0177 (18)0.0093 (17)
O340.071 (3)0.046 (2)0.055 (2)0.0022 (19)0.013 (2)0.0026 (17)
C350.043 (3)0.041 (3)0.048 (3)0.002 (2)0.013 (2)0.002 (2)
C360.0390 (14)0.0343 (14)0.128 (3)0.0002 (11)0.0095 (16)0.0086 (15)
C370.0383 (14)0.0467 (16)0.120 (3)0.0083 (12)0.0144 (17)0.0276 (17)
O380.055 (2)0.057 (2)0.074 (3)0.0097 (19)0.005 (2)0.015 (2)
C390.0490 (16)0.0611 (18)0.107 (2)0.0156 (14)0.0346 (18)0.0437 (19)
Geometric parameters (Å, º) top
S1—O21.4406 (15)C20—H2020.975
S1—O31.4466 (15)C22—C231.400 (3)
S1—C41.756 (2)C22—C271.380 (3)
S1—C51.7743 (18)C23—C241.391 (3)
C4—H410.982C23—H2310.964
C4—H430.957C24—C251.406 (3)
C4—H420.942C24—O281.368 (2)
C5—C61.535 (2)C25—C261.379 (3)
C5—H510.980C25—O311.377 (2)
C5—H520.990C26—C271.396 (3)
C6—N71.475 (2)C26—H2610.922
C6—C221.520 (3)C27—H2710.951
C6—H610.966O28—C291.442 (2)
N7—C81.398 (2)C29—C301.508 (3)
N7—C111.394 (2)C29—H2920.997
C8—C91.478 (3)C29—H2910.973
C8—O121.217 (2)C30—H3010.971
C9—C101.391 (3)C30—H3020.965
C9—C141.390 (3)C30—H3030.952
C10—C111.483 (3)O31—C321.431 (2)
C10—C171.375 (3)C32—H3220.982
C11—O131.216 (2)C32—H3231.018
C14—C151.402 (3)C32—H3210.964
C14—N181.397 (2)O33—C351.320 (6)
C15—C161.394 (3)O33—H3310.839
C15—H1510.934O34—C351.202 (6)
C16—C171.395 (3)C35—C361.421 (5)
C16—H1610.958C36—C36i1.398 (7)
C17—H1710.925C36—C371.347 (4)
N18—C191.367 (2)C36—H3610.950
N18—H1810.848C37—O381.3700 (1)
C19—C201.505 (3)C37—C391.359 (4)
C19—O211.220 (2)C37—H3710.950
C20—H2030.957C39—C39i1.350 (7)
C20—H2010.981C39—H3910.967
O2—S1—O3117.63 (8)C19—C20—H202109.3
O2—S1—C4109.18 (11)H203—C20—H202109.1
O3—S1—C4108.17 (10)H201—C20—H202108.8
O2—S1—C5109.15 (9)C6—C22—C23122.41 (16)
O3—S1—C5109.01 (9)C6—C22—C27118.14 (16)
C4—S1—C5102.66 (9)C23—C22—C27119.45 (17)
S1—C4—H41108.7C22—C23—C24120.39 (17)
S1—C4—H43105.7C22—C23—H231119.6
H41—C4—H43110.2C24—C23—H231120.0
S1—C4—H42108.5C23—C24—C25119.44 (18)
H41—C4—H42112.9C23—C24—O28124.76 (17)
H43—C4—H42110.6C25—C24—O28115.79 (17)
S1—C5—C6113.25 (12)C24—C25—C26120.02 (18)
S1—C5—H51106.8C24—C25—O31115.36 (18)
C6—C5—H51109.8C26—C25—O31124.62 (18)
S1—C5—H52106.1C25—C26—C27120.10 (17)
C6—C5—H52111.4C25—C26—H261121.4
H51—C5—H52109.3C27—C26—H261118.5
C5—C6—N7111.07 (15)C26—C27—C22120.60 (18)
C5—C6—C22111.45 (14)C26—C27—H271120.2
N7—C6—C22112.31 (14)C22—C27—H271119.2
C5—C6—H61109.3C24—O28—C29116.97 (15)
N7—C6—H61103.7O28—C29—C30108.05 (18)
C22—C6—H61108.7O28—C29—H292111.0
C6—N7—C8123.42 (15)C30—C29—H292110.4
C6—N7—C11125.29 (14)O28—C29—H291106.4
C8—N7—C11111.03 (15)C30—C29—H291110.7
N7—C8—C9106.43 (15)H292—C29—H291110.2
N7—C8—O12124.88 (17)C29—C30—H301109.3
C9—C8—O12128.70 (16)C29—C30—H302110.3
C8—C9—C10108.27 (16)H301—C30—H302108.4
C8—C9—C14129.92 (16)C29—C30—H303107.4
C10—C9—C14121.79 (17)H301—C30—H303109.6
C9—C10—C11107.54 (16)H302—C30—H303111.8
C9—C10—C17122.23 (18)C25—O31—C32115.78 (17)
C11—C10—C17130.22 (17)O31—C32—H322105.9
C10—C11—N7106.73 (14)O31—C32—H323109.7
C10—C11—O13128.63 (17)H322—C32—H323111.5
N7—C11—O13124.64 (18)O31—C32—H321110.2
C9—C14—C15116.54 (17)H322—C32—H321108.4
C9—C14—N18118.35 (16)H323—C32—H321111.0
C15—C14—N18125.11 (17)C35—O33—H331120.5
C14—C15—C16120.83 (19)O33—C35—O34122.8 (5)
C14—C15—H151119.3O33—C35—C36120.6 (4)
C16—C15—H151119.9O34—C35—C36116.6 (5)
C15—C16—C17122.20 (19)C35—C36—C36i116.8 (3)
C15—C16—H161117.6C35—C36—C37125.0 (4)
C17—C16—H161120.2C36i—C36—C37116.1 (2)
C16—C17—C10116.38 (18)C35—C36—H3610.1
C16—C17—H171121.3C36i—C36—H361116.7
C10—C17—H171122.3C37—C36—H361125.1
C14—N18—C19128.49 (17)C36—C37—O38119.3 (3)
C14—N18—H181114.5C36—C37—C39127.0 (3)
C19—N18—H181117.0O38—C37—C39113.7 (3)
N18—C19—C20113.96 (17)C36—C37—H371119.3