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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 77| Part 11| November 2021| Pages 1095-1098
https://doi.org/10.1107/S2056989021010392

Crystal structures of two alanyl­piperidine analogues

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Kalina Mambourg,a* Nikolay Tumanov,a Gilles Henon,a Steve Lanners,a Javier Garcia-Ladonab and Johan Woutersa

aDepartment of Chemistry, University of Namur, Rue de Bruxelles 61, Namur 5000, Belgium, and bAbaxys Therapeutics, Rue du Berceau 91, Villers-la-Ville 1495, Belgium
*Correspondence e-mail: kalina.mambourg@unamur.be

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 30 September 2021; accepted 7 October 2021; online 13 October 2021)

The structure of ethyl 1-[N-(4-methyl­phen­yl)-N-(methyl­sulfon­yl)alan­yl]piperidine-4-carboxyl­ate, C19H28N2O5S, I, a compound of inter­est as activator of Ubiquitin C-terminal Hydro­lase-L1 (UCH-L1), was determined by single-crystal X-ray diffraction (SCXRD) analysis. In order to find new activators, a derivative of compound I, namely, 1-[N-(4-methyl­phen­yl)-N-(methyl­sulfon­yl)alan­yl]piperidine-4-carb­oxy­lic acid, C17H24N2O5S, II, was studied. The synthesis and crystal structure are also reported. Despite being analogues, different crystal packings are observed. Compound II bears a carb­oxy­lic group, which favors a strong hydrogen bond. A polymorph risk assessment was carried out to study inter­actions in compound II.

CCDC references: 2114340; 2114339

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1. Chemical context

Ubiquitin C-terminal Hydro­lase-L1 is a deubiquitinase that represents 2% of the neuronal soluble proteins in the brain and is involved in the neuropathogenesis of neurodegenerative diseases. Studies have shown that several mutations have an impact on the hydro­lase activity of UCH-L1 (Leroy et al., 1998[Leroy, E., Boyer, R., Auburger, G., Leube, B., Ulm, G., Mezey, E., Harta, G., Brownstein, M. J., Jonnalagada, S., Chernova, T., Dehejia, A., Lavedan, S., Gasser, T., Steinbach, P. J., Wilkinson, K. D. & Polymeropoulos, M. H. (1998). Nature, 395, 451-452.]; Maraganore et al., 1999[Maraganore, D. M., Farrer, M. J., Hardy, J. A., Lincoln, S. J., McDonnell, S. K. & Rocca, W. A. (1999). Neurology, 53, 1858-1858.]) and that its down-regulation is associated with idiopathic Parkinson's disease (Choi et al., 2004[Choi, J., Levey, A. I., Weintraub, S. T., Rees, H. D., Gearing, M., Chin, L. S. & Li, L. (2004). J. Biol. Chem. 279, 13256-13264.]). Finding potentiators of UCH-L1 could be a therapeutic pathway for these diseases (Mitsui et al., 2010[Mitsui, T., Hirayama, K., Aoki, S., Nishikawa, K., Uchida, K., Matsumoto, T., Kabuta, T. & Wada, K. (2010). Neurochem. Int. 56, 679-686.]). Ethyl 1-[N-(methyl­sulfon­yl)-N-(p-tol­yl)-alan­yl]piperidine-4-carboxyl­ate was discovered through in silico drug screening as an activator of UCH-L1, with a hydro­lase activity up to 111% at 63 µM (Mitsui et al., 2010[Mitsui, T., Hirayama, K., Aoki, S., Nishikawa, K., Uchida, K., Matsumoto, T., Kabuta, T. & Wada, K. (2010). Neurochem. Int. 56, 679-686.]). We studied the only known activator in the literature, compound I. Derivatives of compound I were then investigated as potential activators and compound II was obtained after a saponification. Compound II bears a carb­oxy­lic acid group, which opens up the possibility for co-crystallization and salification in order to modulate the physicochemical properties, such as the solubility. We report the crystal structures of these two compounds as well as a survey of the inter­actions observed in compound II.

[Scheme 1]

2. Structural commentary

Both compounds crystallize as colorless plate-like crystals but in different space groups. Compound I crystallizes in the triclinic P[\overline{1}] space groups and compound II in the monoclinic P21/n space group. The asymmetric units are shown in Fig. 1[link]. Both compounds crystallize as a racemic mixture and have one mol­ecule in the asymmetric unit in a similar conformation. The torsion angle N1—C1—C2—N2 is 156.2 (1) and −153.5 (1)° for I and II respectively. The only slight difference between the two compounds is the geometry of N2. In compound I, the distance between N2 and the plane formed by C2, C3 and C7 is 0.114 (2) Å whereas in compound II this distance is 0.014 (2) Å. A more planar arrangement of N2 in compound II is noticed, probably caused by the crystal packing. Single crystals represent the bulk samples as the powder patterns calculated from SCXRD data are similar to the experimental ones.

[Figure 1]
Figure 1
The asymmetric units of compounds I and II, with displacement ellipsoids drawn at the 50% probability level.

3. Supra­molecular features

As compound I does not have any strong hydrogen-bond acceptors, only weak hydrogen bonds are observed in the crystal structure (see Table 1[link]). The amide oxygen atom O1 participates in the formation of two intra­molecular hydrogen bonds [ S11(7) motifs; Etter et al., 1990[Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256-262.]]. The oxygen atom O4 is inter-connected with atom H12C of the sulfonyl methyl of an adjacent mol­ecule [d(H⋯O) 2.44 Å; Table 1[link]], forming an R22(8) hydrogen bond motif along the a-axis direction (Fig. 2[link]). As compound I bears a tolyl moiety, π–π inter­actions were expected but were not observed in this crystal packing.

Table 1
Hydrogen-bond geometry (Å, °) for compound I[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C12—H12B⋯O1 0.96 2.50 3.210 (2) 130
C12—H12C⋯O4i 0.96 2.44 3.376 (2) 164
C14—H14⋯O1 0.93 2.48 3.177 (2) 132
Symmetry code: (i) [-x, -y, -z+1].
[Figure 2]
Figure 2
Crystal packing of I with hydrogen bonds highlighted in green (a) showing one layer of mol­ecules, viewed down the a axis and (b) showing adjacent layers of mol­ecules.

Compound II bearing a carb­oxy­lic moiety instead of an ester has an impact on the hydrogen bonds and thus on the crystal packing. In compound II, a tubular arrangement (Fig. 3[link]) can be observed, which is different from that of compound I. In compound II, a hydrogen-bonded ring with an R22(24) motif is formed by a strong hydrogen bond between H3 of the carb­oxy­lic acid group and O5 from an adjacent mol­ecule [d(H⋯O) 1.88 (3) Å; Table 2[link]]. In addition, two intra­molecular [ S11(7) motifs] and one inter­molecular [ R22(10) motif] weak hydrogen bonds are detected. As in compound I, no π–π inter­actions are noticed in the crystal structure. A dimer synthon is observed in the crystal packing in both cases, but for compound I it is ensured by weak hydrogen bonds in contrast to compound II where the dimer is based on strong hydrogen bonds.

Table 2
Hydrogen-bond geometry (Å, °) for compound II[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O3—H3⋯O5i 0.90 (3) 1.88 (3) 2.7463 (15) 161 (2)
C17—H17A⋯O1 0.96 2.48 3.144 (2) 127
C4—H4B⋯O2i 0.97 2.52 3.471 (2) 167
C11—H11⋯O1 0.93 2.56 3.2558 (19) 132
Symmetry code: (i) [-x+2, -y+1, -z+1].
[Figure 3]
Figure 3
Crystal packing of II showing the tubular arrangement viewed down the a axis. Hydrogen bonds are highlighted in green.

4. Database survey

Searches of the Cambridge Structural Database (CSD, version 5.42, update September 2021; Groom et al. 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) were carried out with the exact structures of compounds I and II and with substructures containing the significant fragments (alanyl­piperidine with and without the sulfonyl methyl and tolyl group). No comparable structures came out of this survey.

A polymorph risk assessment based on the hydrogen bonds in the CSD was carried out. This statistical analysis allows us to estimate which atoms are the donors and the acceptors for hydrogen bonds in the crystal structure (Chemburkar et al., 2000[Chemburkar, S. R., Bauer, J., Deming, K., Spiwek, H., Patel, K., Morris, J., Henry, R., Spanton, S., Dziki, W., Porter, W., Quick, J., Bauer, P., Donaubauer, J., Narayanan, B. A., Soldani, M., Riley, D. & McFarland, K. (2000). Org. Process Res. Dev. 4, 413-417.]; Galek et al., 2007[Galek, P. T. A., Fábián, L., Motherwell, W. D. S., Allen, F. H. & Feeder, N. (2007). Acta Cryst. B63, 768-782.]). This qu­anti­fies the probability of hydrogen-bond formation and thus the different probable polymorphs that can arise from a specific compound. The results are summarized in Table 3[link]. A hydrogen-bonding inter­action between two carb­oxy­lic groups is predicted with the highest probability. We did not observe the carb­oxy­lic dimer but rather this group inter­acting with one oxygen of the sulfonyl methyl. The analysis also predicts other plausible hydrogen-bonded networks (Fig. 4[link]), one that is statistically slightly more likely to be formed than the current one. This suggests that another potential polymorph could be obtained. Thus, we undertook a polymorph screening by several crystallization experiments of compound II. The recrystallization solvents that we tested were cyclo­hexane, toluene, ethyl acetate, chloro­form, di­chloro­methane, acetone, aceto­nitrile, 2-propanol, ethanol and methanol. They all lead to the same polymorph.

Table 3
Hydrogen-bond propensity calculation for compound II

Donor Acceptor Propensity
O3 O2 0.36
O3 O4 0.30
O3 O5 0.30
[Figure 4]
Figure 4
Hydrogen-bond propensity chart for compound II.

5. Synthesis and crystallization

Compound I: This was purchased from Evotech (Hamburg, Germany). The product was crystallized by slow evaporation from non-anhydrous ethyl acetate, which provided colorless plate-like crystals suitable for SCXRD. M.p. 442.2 K

Compound II: In a round-bottom flask, compound I (405.1 mg, 1.02 mmol, 1.0 eq) dissolved in 8 mL of THF was added to a solution of LiOH (81.9 mg, 3.40 mmol, 3.4 eq) dissolved in 5 mL of water. The mixture was stirred at room temperature for 8 h. The resulting mixture was washed with ether. The aqueous phase was then acidified with HCl 37% to a pH of 2 and extracted with di­chloro­methane. The combined organic phases were dried over anhydrous Na2SO4 and concentrated under vacuum to yield a white solid (351.0 mg, 93%). The product was crystallized by slow evaporation from methanol, which provided colorless plate-like crystals suitable for SCXRD. 1H NMR (DMSO): 12.32 (s, 1H, carb­oxy­lic acid), 7.39 (d, 2H, CHarom), 7.20 (d, 2H, CHarom), 5.20 (s, 1H, CHα), 4.03–3.15 (m, 4H, CHpip), 2.96 (s, 3H, CHSO2Me), 2.79 (m, 1H, CHpip), 2.31 (s, 3H, CHPheMe), 1.83–1.36 (m, 4H, CHpip), 1.03 (d, 3H, CHαMe) 13C NMR (DMSO): 169.1, 168.7, 138.2, 133.5, 132.0, 129.4, 53.3, 44.5, 41.3, 28.5, 20.7, 16.8. M.p. 496.2 K

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4[link]. All H atoms, except one of the -OH group in II, were refined using a riding model, with C—H = 0.93 (aromatic), 0.96 (meth­yl) or 0.98 Å (tertiary carbon). Coordinates of the hydrogen atom of the -OH group were refined. The isotropic atomic displacement parameters of the H atoms were set at 1.5Ueq of the parent atom for the methyl and alcohol groups, and at 1.2Ueq otherwise.

Table 4
Experimental details

  I II
Crystal data
Chemical formula C19H28N2O5S C17H24N2O5S
Mr 396.49 368.44
Crystal system, space group Triclinic, P[\overline{1}] Monoclinic, P21/n
Temperature (K) 295 295
a, b, c (Å) 8.5368 (6), 9.6594 (6), 13.5173 (12) 12.1013 (2), 12.3092 (2), 12.4348 (3)
α, β, γ (°) 75.947 (6), 79.302 (6), 74.554 (5) 90, 100.546 (2), 90
V (Å3) 1033.47 (14) 1820.97 (6)
Z 2 4
Radiation type Mo Kα Mo Kα
μ (mm−1) 0.19 0.21
Crystal size (mm) 0.79 × 0.18 × 0.05 0.77 × 0.18 × 0.11
 
Data collection
Diffractometer Oxford Diffraction Xcalibur, Gemini Ultra R Oxford Diffraction Xcalibur, Gemini Ultra R
Absorption correction Analytical [CrysAlis PRO (Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), based on expressions derived by Clark & Reid (1995[Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897.])] Analytical [CrysAlis PRO (Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), based on expressions derived by Clark & Reid (1995[Clark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887-897.])]
Tmin, Tmax 0.923, 0.991 0.882, 0.980
No. of measured, independent and observed [I > 2σ(I)] reflections 13200, 6870, 4304 29518, 6284, 4779
Rint 0.026 0.026
(sin θ/λ)max (Å−1) 0.762 0.761
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.054, 0.158, 1.02 0.043, 0.126, 1.02
No. of reflections 6870 6284
No. of parameters 248 232
H-atom treatment H-atom parameters constrained H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.34, −0.38 0.29, −0.29
Computer programs: CrysAlis PRO (Rigaku OD, 2018[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), SHELXT2014 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2016 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

CCDC references: 2114340; 2114339

Crystal structure: contains datablocks I, II. DOI: https://doi.org/10.1107/S2056989021010392/vm2254sup1.cif

Supporting information file. DOI: https://doi.org/10.1107/S2056989021010392/vm2254Isup4.mol

Supporting information file. DOI: https://doi.org/10.1107/S2056989021010392/vm2254IIsup5.mol

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989021010392/vm2254Isup6.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989021010392/vm2254Isup6.cml

Structure factors: contains datablock II. DOI: https://doi.org/10.1107/S2056989021010392/vm2254IIsup7.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989021010392/vm2254IIsup7.cml

checkCIF report


Computing details top

For both structures, data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT2014 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

Ethyl 1-[N-(4-methylphenyl)-N-(methylsulfonyl)alanyl]piperidine-4-carboxylate (I) top
Crystal data top
C19H28N2O5SZ = 2
Mr = 396.49F(000) = 424
Triclinic, P1Dx = 1.274 Mg m−3
a = 8.5368 (6) ÅMo Kα radiation, λ = 0.71073 Å
b = 9.6594 (6) ÅCell parameters from 3246 reflections
c = 13.5173 (12) Åθ = 2.4–30.5°
α = 75.947 (6)°µ = 0.19 mm−1
β = 79.302 (6)°T = 295 K
γ = 74.554 (5)°Plate, colorless
V = 1033.47 (14) Å30.79 × 0.18 × 0.05 mm
Data collection top
Oxford Diffraction Xcalibur, Gemini Ultra R
diffractometer		6870 independent reflections
Radiation source: fine-focus sealed X-ray tube4304 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
Detector resolution: 10.3712 pixels mm-1θmax = 32.8°, θmin = 2.2°
ω scansh = −12→10
Absorption correction: analytical
[CrysAlisPro (Rigaku OD, 2018), based on expressions derived by Clark & Reid (1995)]		k = −13→14
Tmin = 0.923, Tmax = 0.991l = −20→19
13200 measured reflections
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullSecondary atom site location: dual
R[F2 > 2σ(F2)] = 0.054Hydrogen site location: mixed
wR(F2) = 0.158H-atom parameters constrained
S = 1.02 w = 1/[σ2(Fo2) + (0.0633P)2 + 0.1206P]
where P = (Fo2 + 2Fc2)/3
6870 reflections(Δ/σ)max < 0.001
248 parametersΔρmax = 0.34 e Å−3
0 restraintsΔρmin = −0.37 e Å−3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.21006 (5)0.11226 (4)0.49970 (3)0.04597 (14)
O10.20546 (16)0.42592 (12)0.58010 (10)0.0542 (3)
O20.2688 (3)−0.0438 (2)1.00683 (16)0.1150 (8)
O30.1551 (3)0.16259 (18)1.06193 (12)0.0894 (5)
O40.21136 (17)0.03480 (13)0.42186 (11)0.0618 (4)
O50.25664 (18)0.02943 (13)0.59697 (11)0.0624 (4)
N10.33461 (16)0.22121 (13)0.45549 (10)0.0404 (3)
N20.3882 (2)0.31933 (16)0.69243 (11)0.0543 (4)
C10.4352 (2)0.24222 (16)0.52607 (12)0.0407 (3)
H10.4849750.1456010.5648650.049*
C20.3309 (2)0.33501 (16)0.60307 (13)0.0435 (4)
C30.2942 (3)0.4081 (2)0.76676 (14)0.0622 (5)
H3A0.2127390.4877530.7334870.075*
H3B0.3670760.4505680.7911430.075*
C40.2099 (3)0.3155 (2)0.85723 (15)0.0598 (5)
H4A0.1269790.2835090.8340390.072*
H4B0.1557210.3743640.9080490.072*
C50.3330 (3)0.1809 (2)0.90679 (14)0.0595 (5)
H50.4090680.2166590.9349030.071*
C60.4334 (3)0.0960 (2)0.82547 (15)0.0631 (5)
H6A0.5170490.0162370.8564660.076*
H6B0.3625400.0541160.7988640.076*
C70.5139 (3)0.1963 (2)0.73772 (15)0.0617 (5)
H7A0.5904250.2333170.7632710.074*
H7B0.5745150.1416840.6856780.074*
C80.2494 (3)0.0852 (2)0.99538 (17)0.0714 (6)
C90.0650 (4)0.0879 (3)1.1529 (2)0.1069 (10)
H9A0.0046260.0294941.1327280.128*
H9B0.1408980.0230641.1987580.128*
C10−0.0456 (5)0.1958 (4)1.2040 (2)0.1357 (14)
H10A0.0122970.2633071.2135280.204*
H10B−0.0915890.1485391.2697790.204*
H10C−0.1319750.2482101.1631320.204*
C110.5719 (2)0.31422 (19)0.46630 (14)0.0503 (4)
H11A0.6369310.2560360.4183340.075*
H11B0.6397300.3215670.5131580.075*
H11C0.5253880.4105640.4296250.075*
C120.0118 (2)0.2217 (2)0.5200 (2)0.0700 (6)
H12A−0.0177460.2839650.4559660.105*
H12B0.0088360.2809540.5682190.105*
H12C−0.0642290.1599860.5468110.105*
C130.3206 (2)0.31143 (16)0.35381 (13)0.0431 (4)
C140.2231 (2)0.45197 (18)0.33966 (14)0.0543 (4)
H140.1668140.4914830.3960390.065*
C150.2097 (3)0.5336 (2)0.24101 (16)0.0641 (5)
H150.1446790.6286040.2320860.077*
C160.2899 (3)0.4784 (2)0.15543 (15)0.0617 (5)
C170.3898 (3)0.3385 (2)0.17173 (16)0.0675 (6)
H170.4475720.2996050.1153950.081*
C180.4060 (3)0.25519 (19)0.26953 (14)0.0569 (5)
H180.4742650.1615200.2786070.068*
C190.2674 (4)0.5688 (3)0.04839 (17)0.0908 (8)
H19A0.1622250.5696190.0322940.136*
H19B0.3519730.526722−0.0005650.136*
H19C0.2737370.6674920.0455820.136*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0381 (2)0.0362 (2)0.0636 (3)−0.00995 (16)−0.00197 (19)−0.01207 (17)
O10.0444 (7)0.0491 (6)0.0645 (8)0.0048 (5)−0.0079 (6)−0.0194 (5)
O20.157 (2)0.0689 (11)0.1072 (15)−0.0226 (12)0.0015 (14)−0.0131 (10)
O30.1050 (15)0.0800 (10)0.0695 (10)−0.0174 (10)0.0144 (9)−0.0133 (8)
O40.0598 (9)0.0532 (7)0.0829 (9)−0.0212 (6)−0.0043 (7)−0.0280 (6)
O50.0629 (9)0.0520 (7)0.0669 (8)−0.0211 (6)−0.0053 (7)0.0039 (6)
N10.0352 (7)0.0367 (6)0.0492 (7)−0.0082 (5)−0.0054 (6)−0.0089 (5)
N20.0541 (10)0.0534 (8)0.0517 (8)0.0017 (7)−0.0076 (7)−0.0191 (6)
C10.0333 (8)0.0376 (7)0.0507 (9)−0.0047 (6)−0.0051 (7)−0.0119 (6)
C20.0389 (9)0.0382 (7)0.0527 (9)−0.0075 (6)−0.0036 (7)−0.0114 (6)
C30.0761 (15)0.0538 (10)0.0557 (11)−0.0053 (10)−0.0049 (10)−0.0226 (8)
C40.0598 (13)0.0600 (11)0.0568 (11)−0.0007 (9)−0.0072 (9)−0.0214 (9)
C50.0600 (13)0.0647 (11)0.0542 (11)−0.0060 (9)−0.0145 (9)−0.0170 (8)
C60.0635 (14)0.0587 (10)0.0620 (12)0.0094 (9)−0.0241 (10)−0.0167 (9)
C70.0490 (12)0.0749 (12)0.0598 (11)0.0038 (9)−0.0152 (9)−0.0247 (9)
C80.0784 (17)0.0663 (13)0.0668 (13)−0.0071 (11)−0.0187 (12)−0.0122 (10)
C90.114 (3)0.0948 (18)0.0859 (19)−0.0194 (18)0.0136 (18)0.0053 (15)
C100.125 (3)0.143 (3)0.092 (2)−0.013 (2)0.033 (2)0.009 (2)
C110.0363 (9)0.0539 (9)0.0644 (11)−0.0139 (7)−0.0001 (8)−0.0200 (8)
C120.0332 (10)0.0571 (11)0.1202 (19)−0.0110 (8)0.0035 (11)−0.0288 (11)
C130.0396 (9)0.0410 (8)0.0493 (9)−0.0094 (7)−0.0059 (7)−0.0105 (6)
C140.0528 (11)0.0484 (9)0.0554 (10)0.0016 (8)−0.0105 (9)−0.0109 (8)
C150.0567 (13)0.0568 (11)0.0695 (13)0.0007 (9)−0.0188 (10)−0.0030 (9)
C160.0607 (13)0.0713 (12)0.0540 (11)−0.0235 (10)−0.0112 (10)−0.0024 (9)
C170.0791 (16)0.0693 (12)0.0534 (11)−0.0223 (11)0.0062 (10)−0.0168 (9)
C180.0627 (13)0.0471 (9)0.0573 (11)−0.0109 (8)0.0035 (9)−0.0143 (8)
C190.092 (2)0.1060 (19)0.0624 (14)−0.0224 (16)−0.0167 (14)0.0085 (13)
Geometric parameters (Å, º) top
S1—O51.4285 (14)C7—H7A0.9700
S1—O41.4286 (13)C7—H7B0.9700
S1—N11.6278 (13)C9—C101.428 (4)
S1—C121.7526 (19)C9—H9A0.9700
O1—C21.227 (2)C9—H9B0.9700
O2—C81.188 (3)C10—H10A0.9600
O3—C81.324 (3)C10—H10B0.9600
O3—C91.462 (3)C10—H10C0.9600
N1—C131.445 (2)C11—H11A0.9600
N1—C11.476 (2)C11—H11B0.9600
N2—C21.346 (2)C11—H11C0.9600
N2—C31.464 (2)C12—H12A0.9600
N2—C71.466 (2)C12—H12B0.9600
C1—C111.519 (2)C12—H12C0.9600
C1—C21.537 (2)C13—C141.380 (2)
C1—H10.9800C13—C181.381 (2)
C3—C41.516 (3)C14—C151.382 (3)
C3—H3A0.9700C14—H140.9300
C3—H3B0.9700C15—C161.379 (3)
C4—C51.535 (3)C15—H150.9300
C4—H4A0.9700C16—C171.384 (3)
C4—H4B0.9700C16—C191.514 (3)
C5—C81.514 (3)C17—C181.381 (3)
C5—C61.526 (3)C17—H170.9300
C5—H50.9800C18—H180.9300
C6—C71.521 (3)C19—H19A0.9600
C6—H6A0.9700C19—H19B0.9600
C6—H6B0.9700C19—H19C0.9600
O5—S1—O4118.43 (8)O2—C8—O3123.4 (2)
O5—S1—N1106.30 (8)O2—C8—C5125.1 (2)
O4—S1—N1108.16 (8)O3—C8—C5111.50 (18)
O5—S1—C12108.50 (11)C10—C9—O3108.7 (2)
O4—S1—C12107.33 (10)C10—C9—H9A110.0
N1—S1—C12107.71 (8)O3—C9—H9A110.0
C8—O3—C9119.1 (2)C10—C9—H9B110.0
C13—N1—C1122.65 (12)O3—C9—H9B110.0
C13—N1—S1117.57 (11)H9A—C9—H9B108.3
C1—N1—S1118.92 (10)C9—C10—H10A109.5
C2—N2—C3119.21 (16)C9—C10—H10B109.5
C2—N2—C7126.42 (15)H10A—C10—H10B109.5
C3—N2—C7112.45 (15)C9—C10—H10C109.5
N1—C1—C11110.73 (13)H10A—C10—H10C109.5
N1—C1—C2111.57 (13)H10B—C10—H10C109.5
C11—C1—C2109.61 (12)C1—C11—H11A109.5
N1—C1—H1108.3C1—C11—H11B109.5
C11—C1—H1108.3H11A—C11—H11B109.5
C2—C1—H1108.3C1—C11—H11C109.5
O1—C2—N2121.94 (15)H11A—C11—H11C109.5
O1—C2—C1120.33 (15)H11B—C11—H11C109.5
N2—C2—C1117.58 (15)S1—C12—H12A109.5
N2—C3—C4110.73 (15)S1—C12—H12B109.5
N2—C3—H3A109.5H12A—C12—H12B109.5
C4—C3—H3A109.5S1—C12—H12C109.5
N2—C3—H3B109.5H12A—C12—H12C109.5
C4—C3—H3B109.5H12B—C12—H12C109.5
H3A—C3—H3B108.1C14—C13—C18119.67 (16)
C3—C4—C5111.24 (18)C14—C13—N1121.20 (15)
C3—C4—H4A109.4C18—C13—N1119.13 (14)
C5—C4—H4A109.4C13—C14—C15119.47 (17)
C3—C4—H4B109.4C13—C14—H14120.3
C5—C4—H4B109.4C15—C14—H14120.3
H4A—C4—H4B108.0C16—C15—C14122.01 (18)
C8—C5—C6112.44 (17)C16—C15—H15119.0
C8—C5—C4111.67 (19)C14—C15—H15119.0
C6—C5—C4110.22 (16)C15—C16—C17117.39 (18)
C8—C5—H5107.4C15—C16—C19120.6 (2)
C6—C5—H5107.4C17—C16—C19122.0 (2)
C4—C5—H5107.4C18—C17—C16121.65 (19)
C7—C6—C5110.66 (16)C18—C17—H17119.2
C7—C6—H6A109.5C16—C17—H17119.2
C5—C6—H6A109.5C13—C18—C17119.76 (17)
C7—C6—H6B109.5C13—C18—H18120.1
C5—C6—H6B109.5C17—C18—H18120.1
H6A—C6—H6B108.1C16—C19—H19A109.5
N2—C7—C6109.70 (17)C16—C19—H19B109.5
N2—C7—H7A109.7H19A—C19—H19B109.5
C6—C7—H7A109.7C16—C19—H19C109.5
N2—C7—H7B109.7H19A—C19—H19C109.5
C6—C7—H7B109.7H19B—C19—H19C109.5
H7A—C7—H7B108.2
O5—S1—N1—C13176.09 (11)C2—N2—C7—C6−103.4 (2)
O4—S1—N1—C1347.92 (13)C3—N2—C7—C660.5 (2)
C12—S1—N1—C13−67.78 (14)C5—C6—C7—N2−57.7 (2)
O5—S1—N1—C1−14.24 (14)C9—O3—C8—O2−2.2 (4)
O4—S1—N1—C1−142.40 (12)C9—O3—C8—C5−179.8 (2)
C12—S1—N1—C1101.89 (14)C6—C5—C8—O26.3 (4)
C13—N1—C1—C11−25.36 (19)C4—C5—C8—O2130.8 (3)
S1—N1—C1—C11165.51 (11)C6—C5—C8—O3−176.2 (2)
C13—N1—C1—C297.02 (16)C4—C5—C8—O3−51.7 (3)
S1—N1—C1—C2−72.11 (15)C8—O3—C9—C10−171.3 (3)
C3—N2—C2—O13.0 (3)C1—N1—C13—C14−76.6 (2)
C7—N2—C2—O1165.98 (18)S1—N1—C13—C1492.68 (17)
C3—N2—C2—C1178.66 (15)C1—N1—C13—C18103.66 (19)
C7—N2—C2—C1−18.4 (3)S1—N1—C13—C18−87.07 (18)
N1—C1—C2—O1−28.1 (2)C18—C13—C14—C151.3 (3)
C11—C1—C2—O194.89 (19)N1—C13—C14—C15−178.45 (17)
N1—C1—C2—N2156.17 (14)C13—C14—C15—C160.7 (3)
C11—C1—C2—N2−80.81 (18)C14—C15—C16—C17−2.1 (3)
C2—N2—C3—C4106.1 (2)C14—C15—C16—C19177.7 (2)
C7—N2—C3—C4−59.1 (2)C15—C16—C17—C181.7 (3)
N2—C3—C4—C554.5 (2)C19—C16—C17—C18−178.1 (2)
C3—C4—C5—C8−178.38 (17)C14—C13—C18—C17−1.7 (3)
C3—C4—C5—C6−52.6 (2)N1—C13—C18—C17178.02 (17)
C8—C5—C6—C7179.54 (18)C16—C17—C18—C130.2 (3)
C4—C5—C6—C754.2 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C12—H12B···O10.962.503.210 (2)130
C12—H12C···O4i0.962.443.376 (2)164
C14—H14···O10.932.483.177 (2)132
Symmetry code: (i) −x, −y, −z+1.
1-[N-(4-methylphenyl)-N-(methylsulfonyl)alanyl]piperidine-4-carboxylic acid (II) top
Crystal data top
C17H24N2O5SF(000) = 784
Mr = 368.44Dx = 1.344 Mg m−3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 12.1013 (2) ÅCell parameters from 8359 reflections
b = 12.3092 (2) Åθ = 2.7–31.5°
c = 12.4348 (3) ŵ = 0.21 mm−1
β = 100.546 (2)°T = 295 K
V = 1820.97 (6) Å3Plate, colorless
Z = 40.77 × 0.18 × 0.11 mm
Data collection top
Oxford Diffraction Xcalibur, Gemini Ultra R
diffractometer		6284 independent reflections
Radiation source: fine-focus sealed X-ray tube4779 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
Detector resolution: 10.3712 pixels mm-1θmax = 32.7°, θmin = 2.2°
ω scansh = −18→18
Absorption correction: analytical
[CrysAlisPro (Rigaku OD, 2018), based on expressions derived by Clark & Reid (1995)]		k = −18→17
Tmin = 0.882, Tmax = 0.980l = −17→18
29518 measured reflections
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullSecondary atom site location: dual
R[F2 > 2σ(F2)] = 0.043Hydrogen site location: difference Fourier map
wR(F2) = 0.126H atoms treated by a mixture of independent and constrained refinement
S = 1.02 w = 1/[σ2(Fo2) + (0.0593P)2 + 0.3685P]
where P = (Fo2 + 2Fc2)/3
6284 reflections(Δ/σ)max = 0.001
232 parametersΔρmax = 0.29 e Å−3
0 restraintsΔρmin = −0.29 e Å−3
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.58667 (2)0.35673 (2)0.60942 (2)0.03513 (9)
O10.68078 (9)0.19851 (8)0.41698 (10)0.0531 (3)
O21.04956 (12)0.60661 (11)0.37887 (13)0.0780 (4)
O31.13713 (10)0.46783 (11)0.31848 (13)0.0732 (4)
H31.195 (2)0.509 (2)0.352 (2)0.110*
O40.50845 (8)0.37442 (9)0.68112 (8)0.0479 (2)
O50.65804 (8)0.44541 (8)0.59029 (9)0.0501 (2)
N10.51748 (8)0.32221 (9)0.48974 (8)0.0344 (2)
N20.73982 (9)0.33804 (10)0.32395 (10)0.0447 (3)
C10.56084 (10)0.35539 (10)0.39054 (10)0.0359 (2)
H10.5806790.4325970.3972400.043*
C170.67424 (14)0.24889 (13)0.66359 (13)0.0555 (4)
H17A0.7266300.2335600.6161940.083*
H17B0.6294020.1855820.6694830.083*
H17C0.7146210.2685080.7347420.083*
C20.66661 (10)0.29079 (11)0.37903 (10)0.0392 (3)
C30.83897 (11)0.27729 (13)0.30503 (13)0.0488 (3)
H3A0.8326980.2631030.2274190.059*
H3B0.8423070.2080020.3426400.059*
C40.94599 (11)0.34095 (12)0.34608 (11)0.0427 (3)
H4A1.0097630.3020940.3277250.051*
H4B0.9570540.3472510.4250850.051*
C50.94003 (11)0.45455 (12)0.29524 (11)0.0438 (3)
H50.9331850.4460180.2159350.053*
C60.83536 (12)0.51356 (12)0.31663 (13)0.0510 (3)
H6A0.8415950.5261010.3945200.061*
H6B0.8293920.5835480.2801820.061*
C70.73079 (12)0.44690 (14)0.27497 (12)0.0510 (4)
H7A0.6655340.4836410.2927480.061*
H7B0.7205570.4405870.1960070.061*
C81.04549 (13)0.51874 (13)0.33621 (12)0.0489 (3)
C90.47176 (12)0.34023 (14)0.28791 (12)0.0489 (3)
H9A0.4580640.2640970.2750370.073*
H9B0.4976920.3717510.2264170.073*
H9C0.4034090.3752860.2976280.073*
C100.42232 (10)0.25039 (10)0.48451 (10)0.0364 (2)
C110.43049 (14)0.14088 (12)0.46161 (15)0.0541 (4)
H110.4987080.1114900.4516880.065*
C120.33581 (16)0.07526 (14)0.45357 (15)0.0641 (4)
H120.3414600.0019340.4373840.077*
C130.23387 (13)0.11605 (14)0.46894 (12)0.0553 (4)
C140.22767 (12)0.22528 (14)0.49295 (13)0.0519 (4)
H140.1598340.2541190.5046700.062*
C150.32057 (10)0.29283 (12)0.49995 (11)0.0423 (3)
H150.3144060.3663720.5149580.051*
C160.13157 (17)0.0435 (2)0.45871 (17)0.0843 (7)
H16A0.0857920.0664680.5099390.126*
H16B0.155060−0.0302460.4739390.126*
H16C0.0889160.0483320.3857440.126*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.03062 (14)0.03481 (15)0.03976 (16)−0.00400 (11)0.00588 (11)−0.00067 (11)
O10.0514 (6)0.0410 (5)0.0722 (7)0.0074 (4)0.0248 (5)0.0058 (5)
O20.0771 (9)0.0640 (8)0.0943 (10)−0.0098 (7)0.0193 (7)−0.0239 (7)
O30.0402 (6)0.0697 (8)0.1097 (11)−0.0137 (5)0.0139 (6)−0.0303 (7)
O40.0448 (5)0.0571 (6)0.0436 (5)−0.0033 (4)0.0129 (4)−0.0075 (4)
O50.0436 (5)0.0481 (5)0.0563 (6)−0.0190 (4)0.0033 (4)0.0010 (4)
N10.0293 (4)0.0375 (5)0.0373 (5)−0.0058 (4)0.0082 (4)−0.0016 (4)
N20.0353 (5)0.0490 (6)0.0530 (6)0.0044 (5)0.0171 (5)0.0037 (5)
C10.0321 (5)0.0382 (6)0.0387 (6)−0.0001 (5)0.0102 (4)0.0020 (5)
C170.0548 (8)0.0583 (9)0.0515 (8)0.0155 (7)0.0051 (7)0.0093 (7)
C20.0345 (6)0.0428 (6)0.0414 (6)0.0005 (5)0.0103 (5)−0.0025 (5)
C30.0366 (6)0.0525 (8)0.0609 (9)0.0005 (6)0.0184 (6)−0.0099 (7)
C40.0360 (6)0.0486 (7)0.0450 (7)0.0029 (5)0.0114 (5)−0.0049 (5)
C50.0388 (6)0.0551 (8)0.0387 (6)−0.0029 (6)0.0107 (5)0.0008 (6)
C60.0493 (8)0.0481 (8)0.0591 (8)0.0065 (6)0.0190 (7)0.0149 (6)
C70.0397 (7)0.0658 (9)0.0499 (8)0.0079 (6)0.0147 (6)0.0195 (7)
C80.0490 (8)0.0517 (8)0.0469 (7)−0.0062 (6)0.0107 (6)−0.0010 (6)
C90.0407 (7)0.0635 (9)0.0411 (7)0.0017 (6)0.0039 (5)0.0014 (6)
C100.0327 (5)0.0359 (6)0.0404 (6)−0.0076 (5)0.0059 (5)0.0002 (5)
C110.0499 (8)0.0397 (7)0.0735 (10)−0.0066 (6)0.0131 (7)−0.0083 (7)
C120.0713 (11)0.0434 (8)0.0759 (11)−0.0228 (8)0.0088 (9)−0.0078 (7)
C130.0513 (8)0.0660 (9)0.0443 (7)−0.0296 (7)−0.0026 (6)0.0081 (7)
C140.0316 (6)0.0692 (10)0.0534 (8)−0.0112 (6)0.0038 (5)0.0085 (7)
C150.0320 (6)0.0447 (7)0.0500 (7)−0.0045 (5)0.0066 (5)0.0028 (5)
C160.0732 (12)0.1026 (16)0.0695 (11)−0.0573 (12)−0.0065 (9)0.0100 (11)
Geometric parameters (Å, º) top
S1—O41.4309 (10)C5—C81.508 (2)
S1—O51.4385 (10)C5—C61.5252 (19)
S1—N11.6249 (10)C5—H50.9800
S1—C171.7543 (15)C6—C71.517 (2)
O1—C21.2300 (16)C6—H6A0.9700
O2—C81.2018 (19)C6—H6B0.9700
O3—C81.3269 (19)C7—H7A0.9700
O3—H30.90 (3)C7—H7B0.9700
N1—C101.4438 (15)C9—H9A0.9600
N1—C11.4834 (15)C9—H9B0.9600
N2—C21.3470 (17)C9—H9C0.9600
N2—C71.4677 (19)C10—C151.3829 (18)
N2—C31.4688 (17)C10—C111.3850 (19)
C1—C91.5238 (18)C11—C121.390 (2)
C1—C21.5356 (17)C11—H110.9300
C1—H10.9800C12—C131.377 (3)
C17—H17A0.9600C12—H120.9300
C17—H17B0.9600C13—C141.382 (2)
C17—H17C0.9600C13—C161.513 (2)
C3—C41.5198 (19)C14—C151.3882 (18)
C3—H3A0.9700C14—H140.9300
C3—H3B0.9700C15—H150.9300
C4—C51.531 (2)C16—H16A0.9600
C4—H4A0.9700C16—H16B0.9600
C4—H4B0.9700C16—H16C0.9600
O4—S1—O5118.24 (6)C7—C6—C5110.50 (13)
O4—S1—N1108.76 (6)C7—C6—H6A109.5
O5—S1—N1105.74 (6)C5—C6—H6A109.5
O4—S1—C17107.33 (7)C7—C6—H6B109.5
O5—S1—C17107.40 (7)C5—C6—H6B109.5
N1—S1—C17109.13 (7)H6A—C6—H6B108.1
C8—O3—H3105.0 (16)N2—C7—C6110.97 (12)
C10—N1—C1122.13 (10)N2—C7—H7A109.4
C10—N1—S1118.32 (8)C6—C7—H7A109.4
C1—N1—S1119.22 (8)N2—C7—H7B109.4
C2—N2—C7126.82 (11)C6—C7—H7B109.4
C2—N2—C3119.62 (12)H7A—C7—H7B108.0
C7—N2—C3113.53 (11)O2—C8—O3122.04 (15)
N1—C1—C9111.04 (10)O2—C8—C5125.76 (15)
N1—C1—C2111.26 (10)O3—C8—C5112.20 (13)
C9—C1—C2109.42 (11)C1—C9—H9A109.5
N1—C1—H1108.3C1—C9—H9B109.5
C9—C1—H1108.3H9A—C9—H9B109.5
C2—C1—H1108.3C1—C9—H9C109.5
S1—C17—H17A109.5H9A—C9—H9C109.5
S1—C17—H17B109.5H9B—C9—H9C109.5
H17A—C17—H17B109.5C15—C10—C11119.68 (12)
S1—C17—H17C109.5C15—C10—N1119.04 (11)
H17A—C17—H17C109.5C11—C10—N1121.26 (12)
H17B—C17—H17C109.5C10—C11—C12119.43 (15)
O1—C2—N2122.37 (12)C10—C11—H11120.3
O1—C2—C1120.17 (11)C12—C11—H11120.3
N2—C2—C1117.44 (11)C13—C12—C11121.70 (16)
N2—C3—C4110.77 (12)C13—C12—H12119.1
N2—C3—H3A109.5C11—C12—H12119.1
C4—C3—H3A109.5C12—C13—C14118.04 (13)
N2—C3—H3B109.5C12—C13—C16120.88 (18)
C4—C3—H3B109.5C14—C13—C16121.08 (18)
H3A—C3—H3B108.1C13—C14—C15121.38 (15)
C3—C4—C5111.06 (12)C13—C14—H14119.3
C3—C4—H4A109.4C15—C14—H14119.3
C5—C4—H4A109.4C10—C15—C14119.76 (14)
C3—C4—H4B109.4C10—C15—H15120.1
C5—C4—H4B109.4C14—C15—H15120.1
H4A—C4—H4B108.0C13—C16—H16A109.5
C8—C5—C6111.72 (13)C13—C16—H16B109.5
C8—C5—C4111.47 (12)H16A—C16—H16B109.5
C6—C5—C4109.92 (11)C13—C16—H16C109.5
C8—C5—H5107.9H16A—C16—H16C109.5
C6—C5—H5107.9H16B—C16—H16C109.5
C4—C5—H5107.9
O4—S1—N1—C10−39.35 (11)C8—C5—C6—C7−179.78 (12)
O5—S1—N1—C10−167.31 (9)C4—C5—C6—C7−55.49 (15)
C17—S1—N1—C1077.45 (11)C2—N2—C7—C6125.15 (15)
O4—S1—N1—C1147.15 (9)C3—N2—C7—C6−56.90 (16)
O5—S1—N1—C119.20 (11)C5—C6—C7—N256.02 (16)
C17—S1—N1—C1−96.05 (11)C6—C5—C8—O2−1.4 (2)
C10—N1—C1—C920.64 (16)C4—C5—C8—O2−124.79 (17)
S1—N1—C1—C9−166.13 (9)C6—C5—C8—O3179.68 (13)
C10—N1—C1—C2−101.50 (13)C4—C5—C8—O356.26 (17)
S1—N1—C1—C271.73 (12)C1—N1—C10—C15−106.70 (14)
C7—N2—C2—O1179.61 (14)S1—N1—C10—C1580.01 (14)
C3—N2—C2—O11.8 (2)C1—N1—C10—C1171.61 (17)
C7—N2—C2—C11.4 (2)S1—N1—C10—C11−101.69 (14)
C3—N2—C2—C1−176.43 (12)C15—C10—C11—C120.5 (2)
N1—C1—C2—O128.24 (17)N1—C10—C11—C12−177.77 (14)
C9—C1—C2—O1−94.83 (15)C10—C11—C12—C13−0.7 (3)
N1—C1—C2—N2−153.51 (11)C11—C12—C13—C140.0 (3)
C9—C1—C2—N283.42 (15)C11—C12—C13—C16179.38 (17)
C2—N2—C3—C4−125.84 (14)C12—C13—C14—C150.9 (2)
C7—N2—C3—C456.05 (17)C16—C13—C14—C15−178.47 (15)
N2—C3—C4—C5−54.68 (15)C11—C10—C15—C140.4 (2)
C3—C4—C5—C8179.52 (11)N1—C10—C15—C14178.68 (12)
C3—C4—C5—C655.07 (15)C13—C14—C15—C10−1.1 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O5i0.90 (3)1.88 (3)2.7463 (15)161 (2)
C17—H17A···O10.962.483.144 (2)127
C4—H4B···O2i0.972.523.471 (2)167
C11—H11···O10.932.563.2558 (19)132
Symmetry code: (i) −x+2, −y+1, −z+1.
Hydrogen-bond propensity calculation for compound II top
DonorAcceptorPropensity
O3O20.36
O3O40.30
O3O50.30
 

Acknowledgements

This work was performed on XRD equipment from the PC2 platform at UNamur and PXRD equipment has been funded by FRS–FNRS. The authors thank Laurie Bodard for her help on the polymorph risk assessment.

References

First citationChemburkar, S. R., Bauer, J., Deming, K., Spiwek, H., Patel, K., Morris, J., Henry, R., Spanton, S., Dziki, W., Porter, W., Quick, J., Bauer, P., Donaubauer, J., Narayanan, B. A., Soldani, M., Riley, D. & McFarland, K. (2000). Org. Process Res. Dev. 4, 413–417.  Web of Science CrossRef CAS Google Scholar
 First citationChoi, J., Levey, A. I., Weintraub, S. T., Rees, H. D., Gearing, M., Chin, L. S. & Li, L. (2004). J. Biol. Chem. 279, 13256–13264.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationClark, R. C. & Reid, J. S. (1995). Acta Cryst. A51, 887–897.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationEtter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256–262.  CrossRef ICSD CAS Web of Science IUCr Journals Google Scholar
 First citationGalek, P. T. A., Fábián, L., Motherwell, W. D. S., Allen, F. H. & Feeder, N. (2007). Acta Cryst. B63, 768–782.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationGroom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179.  Web of Science CrossRef IUCr Journals Google Scholar
 First citationLeroy, E., Boyer, R., Auburger, G., Leube, B., Ulm, G., Mezey, E., Harta, G., Brownstein, M. J., Jonnalagada, S., Chernova, T., Dehejia, A., Lavedan, S., Gasser, T., Steinbach, P. J., Wilkinson, K. D. & Polymeropoulos, M. H. (1998). Nature, 395, 451–452.  Web of Science CrossRef CAS PubMed Google Scholar
 First citationMacrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationMaraganore, D. M., Farrer, M. J., Hardy, J. A., Lincoln, S. J., McDonnell, S. K. & Rocca, W. A. (1999). Neurology, 53, 1858–1858.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationMitsui, T., Hirayama, K., Aoki, S., Nishikawa, K., Uchida, K., Matsumoto, T., Kabuta, T. & Wada, K. (2010). Neurochem. Int. 56, 679–686.  Web of Science CrossRef CAS PubMed Google Scholar
 First citationRigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.  Google Scholar
 First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
 First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
 First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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ISSN: 2056-9890
Volume 77| Part 11| November 2021| Pages 1095-1098
https://doi.org/10.1107/S2056989021010392
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