Febuxostat methanol solvate.

In the title compound {systematic name: [2-(3-cyano-4-isobutyl-oxyphen-yl)-4-methyl-1,3-thia-zole-5-carb-oxy-lic acid (febuxostat) methanol monosolvate}, C(16)H(16)N(2)O(3)S·CH(4)O, the benzene and thia-zole rings in the febuxostat mol-ecule are twisted at 5.3 (1)°. In the crystal structure, inter-molecular O-H⋯O and O-H⋯N hydrogen bonds link the febuxostat and methanol mol-ecules into helical chains along the 2(1) 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 = 348.41

Monoclinic,

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[F 2 > 2σ(F 2)] = 0.043

wR(F 2) = 0.078

S = 1.00

4048 reflections

223 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.13 e Å−3

Δρmin = −0.15 e Å−3

Absolute structure: Flack (1983 ▶), with 1941 Friedel pairs

Flack parameter: −0.05 (7)

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 ▶).

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

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

Supplementary material file. DOI: 10.1107/S1600536811014905/cv5075Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C16H16N2O3S·CH4O	F(000) = 368
Mr = 348.41	Dx = 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

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

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(Fo2) + (0.0221P)2 + 0.134P] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max = 0.002
4048 reflections	Δρmax = 0.13 e Å−3
223 parameters	Δρmin = −0.15 e Å−3
1 restraint	Absolute structure: Flack (1983), with 1941 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: −0.05 (7)

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.

	x	y	z	Uiso*/Ueq
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*

	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)

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)

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

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) .