Febuxostat methanol solvate

Jiang, Q.-Y.; Qian, J.-J.; Gu, J.-M.; Tang, G.-P.; Hu, X.-R.

doi:10.1107/S1600536811014905

organic compounds

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ISSN: 2056-9890

Volume 67| Part 5| May 2011| Page o1232

doi:10.1107/S1600536811014905

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Febuxostat methanol solvate

Qi-Ying Jiang,^a Jing-Jing Qian,^b Jian-Ming Gu,^c Gu-Ping Tang ^a and Xiu-Rong Hu ^c ^*

^aInstitute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China, ^bCollege of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, People's Republic of China, and ^cCenter of Analysis and Measurement, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China
^*Correspondence e-mail: huxiurong@yahoo.com.cn

(Received 12 April 2011; accepted 20 April 2011; online 29 April 2011)

In the title compound {systematic name: [2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic acid (febuxostat) methanol monosolvate}, C₁₆H₁₆N₂O₃S·CH₄O, the benzene and thiazole rings in the febuxostat molecule are twisted at 5.3 (1)°. In the crystal structure, intermolecular O—H⋯O and O—H⋯N hydrogen bonds link the febuxostat and methanol molecules into helical chains along the 2₁ screw axis.

Related literature

For applications of febuxostat in the medicine, see: Schumacher et al. (2009 ); Becke et al. (2010 ); Khosravan et al. (2007 ); Takano et al. (2005 ). For the synthesis, polymorphism, stability and bioavailabitily of febuxostat, see: Hiramatsu et al. (2000 ); Sorbera et al. (2001 ); Zhou et al. (2007 ). For the crystal structure of febuxostat pyridine solvate, see: Zhu et al. (2009 ).

Experimental

Crystal data

C₁₆H₁₆N₂O₃S·CH₄O
M_r = 348.41
Monoclinic, P 2₁
a = 4.7089 (3) Å
b = 17.9073 (13) Å
c = 10.7965 (8) Å
β = 98.047 (2)°
V = 901.44 (11) Å³
Z = 2
Mo Kα radiation
μ = 0.20 mm⁻¹
T = 296 K
0.48 × 0.13 × 0.10 mm

Data collection

Rigaku R-AXIS RAPID/ZJUG diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ) T_min = 0.905, T_max = 0.980
8429 measured reflections
4048 independent reflections
3048 reflections with I > 2σ(I)
R_int = 0.034

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.078
S = 1.00
4048 reflections
223 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Absolute structure: Flack (1983 ), with 1941 Friedel pairs
Flack parameter: −0.05 (7)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯N1ⁱ	0.82	2.09	2.899 (3)	169
O1—H1⋯O4	0.82	1.80	2.608 (3)	166
Symmetry code: (i) $[-x+1, y-{\script{1\over 2}}, -z+2]$ .

Data collection: PROCESS-AUTO (Rigaku, 2006 ); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007 ); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811014905/cv5075sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811014905/cv5075Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811014905/cv5075Isup3.cml

checkCIF report

Comment top

Gout is a disorder caused by deposition of monosodium urate crystals in joints and other tissues as a result of extracellular urate supersaturation. However, hyperuricemia is the most important risk factor for the development of gout and occurs as a result of increased uric acid production (Takano et al., 2005). Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase which is currently under investigation for the management of hyperuricaemia in patients with gout (Khosravan et al., 2007). Many patents and papers have been reported on the synthesis, polymorphism, stability and bioavailabitily of this drug (Hiramatsu et al., 2000; Sorbera et al., 2001; Zhou et al., 2007). The single-crystal structure of febuxostat pyridine solvate has been reported by Zhu et al. (2009). In the present study, we report the crystal structure of febuxostat methanol solvate (I).

The asymmetric unit of (I) consists of one febuxostat molecule and one methanol molecule (Fig. 1). The benzene and thiazole rings of the febuxostat molecule are almost coplanar, with the dihedral angle between them being 5.3 (1)°. The carboxyl group is coplanar with the thiazole ring as indicated by torsion angles O2—C4—C3—C2 and O1—C4—C3—S1 of -0.8 (4)° and -2.5 (3)°, respectively. Conformations of the febuxostat molecule in (I) and in febuxostat pyridine solvate (Zhu et al., 2009) are close.

In the crystal structure, febuxostat molecules and methanol molecule are linked by intermolecular hydrogen bonds O—H···N and O—H···O. In this way, the molecules are linked into infinite zigzag chains stretching along the b axis.

Related literature top

For applications of febuxostat in the medicine, see: Schumacher et al. (2009); Becke et al. (2010); Khosravan et al. (2007); Takano et al. (2005). For synthesis, polymorphism, stability and bioavailabitily of febuxostat, see: Hiramatsu et al. (2000); Sorbera et al. (2001); Zhou et al. (2007). For the crystal structure of febuxostat pyridine solvate, see: Zhu et al. (2009).

Experimental top

The crude product supplied by Zhejiang Huadong Pharmaceutical Co., Ltd, was recrystallized from methanol solution giving colourless crystals suitable for X-ray diffraction.

Computing details top

Data collection: PROCESS-AUTO (Rigaku, 2006); cell refinement: PROCESS-AUTO (Rigaku, 2006); data reduction: CrystalStructure (Rigaku, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. Molecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids drawn at 40% probability level. H atoms are shown as small circles of arbitary radii.
	Fig. 2. A view down the c axis of a portion of the crystal structure showing hydrogen bonds by dashed lines [symmetry codes: (i) 1 - x, -1/2 + y, 2 - z; (ii) 1 - x, 1/2 + y, 2 - z].

[2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-1,3-thiazole-5-carboxylic acid methanol monosolvate top

Crystal data top

C₁₆H₁₆N₂O₃S·CH₄O	F(000) = 368
M_r = 348.41	D_x = 1.284 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 6196 reflections
a = 4.7089 (3) Å	θ = 3.8–27.4°
b = 17.9073 (13) Å	µ = 0.20 mm⁻¹
c = 10.7965 (8) Å	T = 296 K
β = 98.047 (2)°	Needle, colourless
V = 901.44 (11) Å³	0.48 × 0.13 × 0.10 mm
Z = 2

Data collection top

Rigaku R-AXIS RAPID/ZJUG diffractometer	4048 independent reflections
Radiation source: rolling anode	3048 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.034
Detector resolution: 10.00 pixels mm^-1	θ_max = 27.4°, θ_min = 3.8°
ω scans	h = −5→6
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −23→23
T_min = 0.905, T_max = 0.980	l = −13→13
8429 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.043	H-atom parameters constrained
wR(F²) = 0.078	w = 1/[σ²(F_o²) + (0.0221P)² + 0.134P] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max = 0.002
4048 reflections	Δρ_max = 0.13 e Å⁻³
223 parameters	Δρ_min = −0.15 e Å⁻³
1 restraint	Absolute structure: Flack (1983), with 1941 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.05 (7)

Crystal data top

C₁₆H₁₆N₂O₃S·CH₄O	V = 901.44 (11) Å³
M_r = 348.41	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 4.7089 (3) Å	µ = 0.20 mm⁻¹
b = 17.9073 (13) Å	T = 296 K
c = 10.7965 (8) Å	0.48 × 0.13 × 0.10 mm
β = 98.047 (2)°

Data collection top

Rigaku R-AXIS RAPID/ZJUG diffractometer	4048 independent reflections
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	3048 reflections with I > 2σ(I)
T_min = 0.905, T_max = 0.980	R_int = 0.034
8429 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	H-atom parameters constrained
wR(F²) = 0.078	Δρ_max = 0.13 e Å⁻³
S = 1.00	Δρ_min = −0.15 e Å⁻³
4048 reflections	Absolute structure: Flack (1983), with 1941 Friedel pairs
223 parameters	Absolute structure parameter: −0.05 (7)
1 restraint

Special details top

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O4	0.2078 (5)	0.19681 (11)	0.8788 (2)	0.0794 (6)
H4	0.2298	0.1575	0.9181	0.119*
C17	0.0129 (8)	0.1856 (2)	0.7690 (3)	0.0918 (10)
H17A	−0.1528	0.1595	0.7890	0.138*
H17B	0.1031	0.1567	0.7106	0.138*
H17C	−0.0445	0.2331	0.7324	0.138*
S1	0.81600 (13)	0.45188 (3)	0.82299 (5)	0.04563 (15)
N1	0.7895 (4)	0.56137 (10)	0.97388 (17)	0.0410 (4)
O3	1.6085 (4)	0.72442 (8)	0.62269 (15)	0.0491 (4)
C6	1.0840 (5)	0.59027 (12)	0.8089 (2)	0.0377 (5)
C8	1.3569 (5)	0.61374 (13)	0.6395 (2)	0.0411 (6)
C1	0.8996 (5)	0.54145 (12)	0.8730 (2)	0.0403 (5)
C13	1.6920 (5)	0.79823 (12)	0.6671 (2)	0.0465 (6)
H13A	1.8109	0.7952	0.7479	0.056*
H13B	1.5232	0.8276	0.6764	0.056*
O1	0.5033 (5)	0.31992 (10)	0.87756 (19)	0.0708 (6)
H1	0.4149	0.2820	0.8907	0.106*
C3	0.6208 (5)	0.44077 (13)	0.9457 (2)	0.0420 (6)
C14	1.8573 (6)	0.83447 (13)	0.5728 (2)	0.0504 (6)
H14	2.0217	0.8026	0.5625	0.060*
C2	0.6304 (5)	0.50420 (13)	1.0150 (2)	0.0416 (5)
C11	1.1728 (5)	0.65996 (13)	0.8577 (2)	0.0463 (6)
H11	1.1123	0.6757	0.9318	0.056*
O2	0.3404 (4)	0.35831 (10)	1.05077 (18)	0.0692 (5)
C9	1.4399 (5)	0.68379 (13)	0.6888 (2)	0.0406 (5)
C7	1.1807 (5)	0.56763 (12)	0.6989 (2)	0.0443 (6)
H7	1.1269	0.5212	0.6648	0.053*
C10	1.3472 (5)	0.70618 (13)	0.7997 (2)	0.0453 (6)
H10	1.4029	0.7523	0.8346	0.054*
C4	0.4753 (5)	0.36987 (14)	0.9650 (2)	0.0480 (6)
C12	1.4636 (6)	0.58932 (14)	0.5282 (3)	0.0572 (7)
C5	0.4890 (6)	0.51762 (15)	1.1292 (2)	0.0568 (7)
H5A	0.6307	0.5160	1.2023	0.085*
H5B	0.3475	0.4797	1.1352	0.085*
H5C	0.3982	0.5657	1.1233	0.085*
C16	1.9705 (7)	0.90956 (14)	0.6279 (3)	0.0750 (9)
H16A	2.0798	0.9015	0.7087	0.113*
H16B	1.8119	0.9420	0.6359	0.113*
H16C	2.0906	0.9321	0.5734	0.113*
N2	1.5505 (7)	0.56898 (16)	0.4403 (3)	0.0918 (9)
C15	1.6760 (7)	0.8435 (2)	0.4470 (3)	0.0838 (10)
H15A	1.5222	0.8777	0.4543	0.126*
H15B	1.5982	0.7959	0.4189	0.126*
H15C	1.7922	0.8626	0.3879	0.126*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.1106 (17)	0.0497 (12)	0.0779 (14)	−0.0241 (12)	0.0131 (14)	0.0098 (11)
C17	0.102 (3)	0.086 (2)	0.088 (2)	−0.013 (2)	0.017 (2)	0.012 (2)
S1	0.0576 (3)	0.0349 (3)	0.0467 (3)	−0.0026 (3)	0.0151 (3)	−0.0007 (3)
N1	0.0452 (10)	0.0372 (10)	0.0415 (10)	0.0046 (9)	0.0089 (9)	0.0009 (8)
O3	0.0636 (11)	0.0400 (9)	0.0473 (9)	−0.0117 (8)	0.0204 (9)	−0.0047 (7)
C6	0.0410 (12)	0.0334 (11)	0.0389 (12)	0.0016 (10)	0.0058 (10)	0.0038 (10)
C8	0.0465 (14)	0.0380 (12)	0.0399 (13)	−0.0025 (11)	0.0101 (11)	−0.0030 (10)
C1	0.0435 (13)	0.0358 (12)	0.0407 (12)	0.0018 (10)	0.0029 (11)	0.0024 (10)
C13	0.0519 (14)	0.0375 (12)	0.0509 (14)	−0.0060 (12)	0.0101 (12)	−0.0024 (11)
O1	0.1015 (16)	0.0449 (11)	0.0727 (13)	−0.0199 (10)	0.0356 (12)	−0.0043 (10)
C3	0.0475 (13)	0.0388 (14)	0.0408 (12)	0.0016 (11)	0.0097 (10)	0.0076 (11)
C14	0.0499 (14)	0.0417 (14)	0.0627 (16)	−0.0004 (11)	0.0194 (13)	0.0036 (12)
C2	0.0424 (14)	0.0426 (13)	0.0402 (13)	0.0074 (11)	0.0069 (11)	0.0075 (10)
C11	0.0565 (15)	0.0422 (14)	0.0407 (13)	−0.0020 (12)	0.0089 (12)	−0.0045 (11)
O2	0.0964 (15)	0.0531 (11)	0.0647 (12)	−0.0073 (10)	0.0341 (12)	0.0151 (9)
C9	0.0456 (13)	0.0357 (12)	0.0408 (13)	−0.0004 (10)	0.0072 (11)	0.0025 (10)
C7	0.0503 (13)	0.0351 (12)	0.0473 (13)	−0.0029 (11)	0.0062 (11)	−0.0024 (11)
C10	0.0595 (16)	0.0345 (12)	0.0427 (13)	−0.0059 (11)	0.0105 (12)	−0.0027 (10)
C4	0.0562 (15)	0.0423 (13)	0.0452 (14)	0.0044 (12)	0.0057 (13)	0.0100 (12)
C12	0.0730 (18)	0.0450 (14)	0.0577 (16)	−0.0140 (13)	0.0229 (14)	−0.0090 (13)
C5	0.0666 (17)	0.0557 (16)	0.0531 (16)	0.0009 (13)	0.0252 (14)	0.0004 (12)
C16	0.074 (2)	0.0436 (16)	0.113 (3)	−0.0099 (14)	0.0326 (19)	−0.0034 (16)
N2	0.126 (2)	0.085 (2)	0.0752 (18)	−0.0245 (18)	0.0498 (18)	−0.0323 (16)
C15	0.100 (3)	0.087 (2)	0.067 (2)	−0.004 (2)	0.0197 (19)	0.0235 (17)

Geometric parameters (Å, º) top

O4—C17	1.409 (4)	C3—C2	1.357 (3)
O4—H4	0.8200	C3—C4	1.471 (3)
C17—H17A	0.9600	C14—C15	1.508 (4)
C17—H17B	0.9600	C14—C16	1.535 (4)
C17—H17C	0.9600	C14—H14	0.9800
S1—C1	1.720 (2)	C2—C5	1.501 (3)
S1—C3	1.727 (2)	C11—C10	1.377 (3)
N1—C1	1.319 (3)	C11—H11	0.9300
N1—C2	1.378 (3)	O2—C4	1.211 (3)
O3—C9	1.352 (3)	C9—C10	1.389 (3)
O3—C13	1.442 (3)	C7—H7	0.9300
C6—C7	1.390 (3)	C10—H10	0.9300
C6—C11	1.396 (3)	C12—N2	1.144 (3)
C6—C1	1.472 (3)	C5—H5A	0.9600
C8—C7	1.389 (3)	C5—H5B	0.9600
C8—C9	1.397 (3)	C5—H5C	0.9600
C8—C12	1.435 (4)	C16—H16A	0.9600
C13—C14	1.512 (3)	C16—H16B	0.9600
C13—H13A	0.9700	C16—H16C	0.9600
C13—H13B	0.9700	C15—H15A	0.9600
O1—C4	1.321 (3)	C15—H15B	0.9600
O1—H1	0.8200	C15—H15C	0.9600

C17—O4—H4	109.5	C3—C2—C5	127.0 (2)
O4—C17—H17A	109.5	N1—C2—C5	118.0 (2)
O4—C17—H17B	109.5	C10—C11—C6	122.1 (2)
H17A—C17—H17B	109.5	C10—C11—H11	118.9
O4—C17—H17C	109.5	C6—C11—H11	118.9
H17A—C17—H17C	109.5	O3—C9—C10	125.3 (2)
H17B—C17—H17C	109.5	O3—C9—C8	115.8 (2)
C1—S1—C3	89.40 (12)	C10—C9—C8	118.8 (2)
C1—N1—C2	111.03 (19)	C6—C7—C8	120.6 (2)
C9—O3—C13	118.06 (17)	C6—C7—H7	119.7
C7—C6—C11	117.8 (2)	C8—C7—H7	119.7
C7—C6—C1	120.9 (2)	C11—C10—C9	119.9 (2)
C11—C6—C1	121.3 (2)	C11—C10—H10	120.1
C7—C8—C9	120.8 (2)	C9—C10—H10	120.1
C7—C8—C12	120.5 (2)	O2—C4—O1	123.1 (2)
C9—C8—C12	118.7 (2)	O2—C4—C3	124.1 (2)
N1—C1—C6	123.6 (2)	O1—C4—C3	112.8 (2)
N1—C1—S1	114.35 (17)	N2—C12—C8	179.0 (3)
C6—C1—S1	122.03 (18)	C2—C5—H5A	109.5
O3—C13—C14	108.14 (19)	C2—C5—H5B	109.5
O3—C13—H13A	110.1	H5A—C5—H5B	109.5
C14—C13—H13A	110.1	C2—C5—H5C	109.5
O3—C13—H13B	110.1	H5A—C5—H5C	109.5
C14—C13—H13B	110.1	H5B—C5—H5C	109.5
H13A—C13—H13B	108.4	C14—C16—H16A	109.5
C4—O1—H1	109.5	C14—C16—H16B	109.5
C2—C3—C4	128.6 (2)	H16A—C16—H16B	109.5
C2—C3—S1	110.26 (18)	C14—C16—H16C	109.5
C4—C3—S1	121.10 (18)	H16A—C16—H16C	109.5
C15—C14—C13	111.9 (2)	H16B—C16—H16C	109.5
C15—C14—C16	112.2 (2)	C14—C15—H15A	109.5
C13—C14—C16	107.4 (2)	C14—C15—H15B	109.5
C15—C14—H14	108.4	H15A—C15—H15B	109.5
C13—C14—H14	108.4	C14—C15—H15C	109.5
C16—C14—H14	108.4	H15A—C15—H15C	109.5
C3—C2—N1	115.0 (2)	H15B—C15—H15C	109.5

C2—N1—C1—C6	−178.87 (19)	C7—C6—C11—C10	0.9 (3)
C2—N1—C1—S1	−0.2 (2)	C1—C6—C11—C10	179.5 (2)
C7—C6—C1—N1	−176.4 (2)	C13—O3—C9—C10	−2.4 (3)
C11—C6—C1—N1	5.0 (3)	C13—O3—C9—C8	177.84 (19)
C7—C6—C1—S1	5.0 (3)	C7—C8—C9—O3	−179.2 (2)
C11—C6—C1—S1	−173.57 (17)	C12—C8—C9—O3	2.6 (3)
C3—S1—C1—N1	0.00 (18)	C7—C8—C9—C10	1.1 (3)
C3—S1—C1—C6	178.72 (18)	C12—C8—C9—C10	−177.2 (2)
C9—O3—C13—C14	−175.41 (19)	C11—C6—C7—C8	−0.8 (3)
C1—S1—C3—C2	0.17 (18)	C1—C6—C7—C8	−179.4 (2)
C1—S1—C3—C4	−179.20 (18)	C9—C8—C7—C6	−0.2 (3)
O3—C13—C14—C15	62.2 (3)	C12—C8—C7—C6	178.1 (2)
O3—C13—C14—C16	−174.3 (2)	C6—C11—C10—C9	0.1 (4)
C4—C3—C2—N1	179.0 (2)	O3—C9—C10—C11	179.3 (2)
S1—C3—C2—N1	−0.3 (2)	C8—C9—C10—C11	−1.0 (3)
C4—C3—C2—C5	−0.8 (4)	C2—C3—C4—O2	−0.8 (4)
S1—C3—C2—C5	179.91 (19)	S1—C3—C4—O2	178.45 (19)
C1—N1—C2—C3	0.3 (3)	C2—C3—C4—O1	178.3 (2)
C1—N1—C2—C5	−179.9 (2)	S1—C3—C4—O1	−2.5 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N1ⁱ	0.82	2.09	2.899 (3)	169
O1—H1···O4	0.82	1.80	2.608 (3)	166

Symmetry code: (i) −x+1, y−1/2, −z+2.

Experimental details

Crystal data
Chemical formula	C₁₆H₁₆N₂O₃S·CH₄O
M_r	348.41
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	296
a, b, c (Å)	4.7089 (3), 17.9073 (13), 10.7965 (8)
β (°)	98.047 (2)
V (Å³)	901.44 (11)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.20
Crystal size (mm)	0.48 × 0.13 × 0.10

Data collection
Diffractometer	Rigaku R-AXIS RAPID/ZJUG diffractometer
Absorption correction	Multi-scan (ABSCOR; Higashi, 1995)
T_min, T_max	0.905, 0.980
No. of measured, independent and observed [I > 2σ(I)] reflections	8429, 4048, 3048
R_int	0.034
(sin θ/λ)_max (Å⁻¹)	0.648

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.078, 1.00
No. of reflections	4048
No. of parameters	223
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.13, −0.15
Absolute structure	Flack (1983), with 1941 Friedel pairs
Absolute structure parameter	−0.05 (7)

Computer programs: PROCESS-AUTO (Rigaku, 2006), CrystalStructure (Rigaku, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N1ⁱ	0.82	2.09	2.899 (3)	169
O1—H1···O4	0.82	1.80	2.608 (3)	166

Symmetry code: (i) −x+1, y−1/2, −z+2.

Acknowledgements

The project was supported by Zhejiang Provincial Natural Science Foundation of China (grant No. J200801).

References

Becke, M. A., Schumacher, H. R., Espinoza, L. R., Wells, A. F., Macdonald, P., Lloyd, E. & Lademacher, C. (2010). Arthritis Res. Ther. 12, R63, 1–12. Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan. Google Scholar
Hiramatsu, T., Matsumoto, K. & Watanabe, K. (2000). China Patent CN 1275126. Google Scholar
Khosravan, R., Grabowski, B., Wu, J. T., Joseph-Ridge, N. & Vernillet, L. (2007). Clin. Pharm. 65, 355–363. CrossRef Google Scholar
Rigaku (2006). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan. Google Scholar
Rigaku (2007). CrystalStructure. Rigaku Corporation, Tokyo, Japan. Google Scholar
Schumacher, H. R., Becker, M. A., Lloyd, E., Macdonald, P. A. & Lademacher, C. (2009). Rheumatology, 48, 188–194. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sorbera, L. A., Revel, L., Rabasseda, X. & Castaner, J. (2001). Drugs Fut. 26, 32–38. CAS Google Scholar
Takano, Y., Hase-Aoki, K., Horiuchi, H., Zhao, L., Kasahara, Y., Kondo, S. & Becker, M. A. (2005). Life Sci. 76, 1835–1847. Web of Science CrossRef PubMed CAS Google Scholar
Zhou, X. G., Tang, X. M., Deng, J., Ye, W. R., Luo, J., Zhang, D. L. & Fan, B. (2007). China Patent CN 1970547. Google Scholar
Zhu, X., Wang, Y. & Lu, T. (2009). Acta Cryst. E65, o2603. Web of Science CrossRef IUCr Journals Google Scholar