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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 65| Part 11| November 2009| Page o2603
https://doi.org/10.1107/S1600536809039002

2-[3-Cyano-4-(2-methyl­prop­­oxy)phen­yl]-4-methyl­thia­zole-5-carboxylic acid pyridine solvate

Xiong Zhu,a Yue Wangb and Tao Lub*

aInstitute of Medicine, China Pharmaceutical University, Nanjing 210009, People's Republic of China, and bCollege of Basic Sciences, China Pharmaceutical University, Nanjing 210009, People's Republic of China
*Correspondence e-mail: lut163@163.com

(Received 12 August 2009; accepted 25 September 2009; online 3 October 2009)

In the title compound, C16H16N2O3S·C5H5N, the benzene and thia­zole rings of the Febuxostat [2-(3-cyano-4-isobut­yloxy)phenyl-4-methyl-5-thia­zolecarboxylic acid] mol­ecule are almost coplanar [dihedral angle = 2.4 (1)°]. The carboxyl group is coplanar with the thia­zole ring [O—C—C—C and O—C—C—S torsion angles of −0.7 (4) and 0.6 (3)°, respectively]. The pyridine mol­ecule of crystallization is linked to the Febuxostat mol­ecule through an O—H⋯N hydrogen bond. A weak π–π stacking inter­action is observed between the benzene ring of the Febuxostat mol­ecule and pyridine mol­ecule, with a centroid–centroid distance of 3.7530 (18) Å.

Related literature

For general background to gout, see: Alexander (2008[Alexander, S. (2008). Arthritis Res. Ther. 10, 221-227.]). For the synthesis, polymorphism, stability and biological activity of Febuxostat, see: Edwards (2009[Edwards, N. L. (2009). Rheumatology, 48, 15-19.]); Hiramatsu et al. (2000[Hiramatsu, T., Matsumoto, K. & Watanabe, K. (2000). China Patent CN1 275 126.]); Perez-Ruiz et al. (2008[Perez-Ruiz, F., Dalbeth, N. & Schlesinger, N. (2008). Future Rheumatol. 3, 421-427.]); Sorbera et al. (2001[Sorbera, L. A., Revel, L., Rabasseda, X. & Castaner, J. (2001). Drugs Fut. 26, 32-38.]); Zhou et al. (2007[Zhou, X. G., Tang, X. M., Deng, J., Ye, W. R., Luo, J., Luo, J., Zhang, D. L. & Fan, B. (2007). China Patent CN1 970 547.]). For a related structure, see: Fontrodona et al. (2001[Fontrodona, X., Diaz, S., Linden, A. & Villalgordo, J. M. (2001). Synthesis, pp. 2021-2027.]).

[Scheme 1]

Experimental

Crystal data

  • C16H16N2O3S·C5H5N

  • Mr = 395.47

  • Triclinic, [P \overline 1]

  • a = 8.6040 (17) Å

  • b = 10.339 (2) Å

  • c = 12.611 (3) Å

  • α = 82.51 (3)°

  • β = 80.69 (3)°

  • γ = 69.61 (3)°

  • V = 1034.4 (4) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.18 mm−1

  • T = 296 K

  • 0.30 × 0.20 × 0.20 mm
Data collection

  • Enraf–Nonius CAD-4 diffractometer

  • Absorption correction: ψ scan (North et al., 1968[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.947, Tmax = 0.964

  • 4017 measured reflections

  • 3747 independent reflections

  • 2815 reflections with I > 2σ(I)

  • Rint = 0.032

  • 3 standard reflections every 200 reflections intensity decay: 1%
Refinement

  • R[F2 > 2σ(F2)] = 0.049

  • wR(F2) = 0.156

  • S = 0.99

  • 3747 reflections

  • 255 parameters

  • H-atom parameters constrained

  • Δρmax = 0.33 e Å−3

  • Δρmin = −0.19 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O2—H2A⋯N3i 0.82 1.79 2.611 (3) 174
Symmetry code: (i) x, y, z-1.

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994[Enraf-Nonius (1994). CAD-4 EXPRESS. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo,1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536809039002/ci2885sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536809039002/ci2885Isup2.hkl

checkCIF report


Comment top

The oxidation of xanthine results in the formation of uric acid. Disorders of uric acid metabolism include gout which is the most common inflammatory arthritis initiated by tissue deposition of monosodium urate (MSU) crystals (Alexander, 2008). Some inventions are related to methods of preserving or increasing renal function in a subject by administering a therapeutically effective amount of at least one xanthine oxidoreductase inhibiting compound. 2-(3-Cyano-4-isobutyloxy)phenyl-4-methyl-5-thiazolecarboxylic acid (Febuxostat) is one of the novel drug that have been evaluated and shown to be highly effective in the management of hyperuricemia (Perez-Ruiz et al., 2008; Edwards, 2009), thus enlarging the therapeutic options available to lower uric acid levels. Many patents or papers have been reported on the synthesis, polymorphism and their effect on the stability and bioavailability of this drug (Hiramatsu et al., 2000; Sorbera et al., 2001; Zhou et al., 2007). However, there are few reports on its single-crystal structure. In the present study, we report the crystal structure of the title compound.

The asymmetric unit of the title compound contains one febuxostat molecule and one pyridine molecule. The phenyl ring and thiazole rings of the febuxostat molecule are almost coplanar (Fig. 1), with the dihedral angle between them being 2.4 (1)°. The carboxyl group is coplanar with the thiazole ring as indicated by torsion angles O1—C1—C2—C4 and O2—C1—C2—S of -0.7 (4)° and 0.6 (3)°, respectively. Bond lengths and angles are comparable to those observed in a related structure (Fontrodona et al., 2001).

In the crystal, pyridine moleclue is linked to the febuxostat molecule through a O2—H2A···N3(x, y, 1 + z) hydrogen bond (Table 1). A weak π-π stacking interaction is observed between the benzene ring and pyridine molecule, with a centroid-to-centroid distance of 3.7530 (18) Å.

Related literature top

For general background to gout, see: Alexander (2008). For the synthesis, polymorphism, stability and biological activity of Febuxostat, see: Edwards (2009); Hiramatsu et al. (2000); Perez-Ruiz et al. (2008); Sorbera et al. (2001); Zhou et al. (2007). For a related structure, see: Fontrodona et al. (2001).

Experimental top

2-(3-Formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (42.6 g, 0.123 mol) was treated with formic acid (384 ml), sodium formate (15.3 g, 0.147 mol) and hydroxylamine hydrochloride (10.2 g, 0.147 mol) to give 21.4 g of 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid ethyl ester (yield 50.5%). Then it was hydrolyzed with NaOH in tetrahydrofuran and ethanol. Finally, brown block crystals of the title compound appropriate for X-ray data collection were obtained by slow evaporation of a pyridine solution at room temperature (yield 70%).

Refinement top

All H atoms were initially located from a difference Fourier map and then were regenerated at ideal positions and treated as riding, with O-H = 0.82 Å, C-H = 0.93-0.98 Å and Uiso(H) = 1.2-1.5Ueq(C,O).

Structure description top

The oxidation of xanthine results in the formation of uric acid. Disorders of uric acid metabolism include gout which is the most common inflammatory arthritis initiated by tissue deposition of monosodium urate (MSU) crystals (Alexander, 2008). Some inventions are related to methods of preserving or increasing renal function in a subject by administering a therapeutically effective amount of at least one xanthine oxidoreductase inhibiting compound. 2-(3-Cyano-4-isobutyloxy)phenyl-4-methyl-5-thiazolecarboxylic acid (Febuxostat) is one of the novel drug that have been evaluated and shown to be highly effective in the management of hyperuricemia (Perez-Ruiz et al., 2008; Edwards, 2009), thus enlarging the therapeutic options available to lower uric acid levels. Many patents or papers have been reported on the synthesis, polymorphism and their effect on the stability and bioavailability of this drug (Hiramatsu et al., 2000; Sorbera et al., 2001; Zhou et al., 2007). However, there are few reports on its single-crystal structure. In the present study, we report the crystal structure of the title compound.

The asymmetric unit of the title compound contains one febuxostat molecule and one pyridine molecule. The phenyl ring and thiazole rings of the febuxostat molecule are almost coplanar (Fig. 1), with the dihedral angle between them being 2.4 (1)°. The carboxyl group is coplanar with the thiazole ring as indicated by torsion angles O1—C1—C2—C4 and O2—C1—C2—S of -0.7 (4)° and 0.6 (3)°, respectively. Bond lengths and angles are comparable to those observed in a related structure (Fontrodona et al., 2001).

In the crystal, pyridine moleclue is linked to the febuxostat molecule through a O2—H2A···N3(x, y, 1 + z) hydrogen bond (Table 1). A weak π-π stacking interaction is observed between the benzene ring and pyridine molecule, with a centroid-to-centroid distance of 3.7530 (18) Å.

For general background to gout, see: Alexander (2008). For the synthesis, polymorphism, stability and biological activity of Febuxostat, see: Edwards (2009); Hiramatsu et al. (2000); Perez-Ruiz et al. (2008); Sorbera et al. (2001); Zhou et al. (2007). For a related structure, see: Fontrodona et al. (2001).

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1994); data reduction: XCAD4 (Harms & Wocadlo,1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing 50% probability displacement ellipsoids.
2-[3-Cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid pyridine solvate top
Crystal data top
C16H16N2O3S·C5H5NZ = 2
Mr = 395.47F(000) = 416
Triclinic, P1Dx = 1.270 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.6040 (17) ÅCell parameters from 25 reflections
b = 10.339 (2) Åθ = 10–13°
c = 12.611 (3) ŵ = 0.18 mm−1
α = 82.51 (3)°T = 296 K
β = 80.69 (3)°Block, brown
γ = 69.61 (3)°0.30 × 0.20 × 0.20 mm
V = 1034.4 (4) Å3
Data collection top
Enraf–Nonius CAD-4
diffractometer		2815 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.032
Graphite monochromatorθmax = 25.3°, θmin = 1.6°
ω/2θ scansh = 0→10
Absorption correction: ψ scan
(North et al., 1968)		k = −11→12
Tmin = 0.947, Tmax = 0.964l = −14→15
4017 measured reflections3 standard reflections every 200 reflections
3747 independent reflections intensity decay: 1%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049H-atom parameters constrained
wR(F2) = 0.156 w = 1/[σ2(Fo2) + (0.1P)2 + 0.12P]
where P = (Fo2 + 2Fc2)/3
S = 0.99(Δ/σ)max = 0.001
3747 reflectionsΔρmax = 0.33 e Å−3
255 parametersΔρmin = −0.19 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.030 (5)
Crystal data top
C16H16N2O3S·C5H5Nγ = 69.61 (3)°
Mr = 395.47V = 1034.4 (4) Å3
Triclinic, P1Z = 2
a = 8.6040 (17) ÅMo Kα radiation
b = 10.339 (2) ŵ = 0.18 mm−1
c = 12.611 (3) ÅT = 296 K
α = 82.51 (3)°0.30 × 0.20 × 0.20 mm
β = 80.69 (3)°
Data collection top
Enraf–Nonius CAD-4
diffractometer		2815 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.032
Tmin = 0.947, Tmax = 0.9643 standard reflections every 200 reflections
4017 measured reflections intensity decay: 1%
3747 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0490 restraints
wR(F2) = 0.156H-atom parameters constrained
S = 0.99Δρmax = 0.33 e Å−3
3747 reflectionsΔρmin = −0.19 e Å−3
255 parameters
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
xyzUiso*/Ueq
S0.83182 (8)0.26459 (7)0.30078 (4)0.0564 (2)
O10.5471 (2)0.2112 (2)0.10983 (14)0.0754 (6)
O20.7344 (2)0.3198 (2)0.08925 (14)0.0754 (6)
H2A0.70910.33810.02770.113*
O31.1361 (2)0.20514 (18)0.76698 (12)0.0586 (5)
N10.6870 (3)0.1219 (2)0.43509 (15)0.0586 (5)
N21.2786 (4)0.4042 (4)0.5613 (2)0.1041 (10)
C10.6483 (3)0.2464 (3)0.14487 (19)0.0570 (6)
C20.6882 (3)0.2095 (3)0.25744 (18)0.0523 (6)
C30.7976 (3)0.1847 (2)0.42631 (17)0.0510 (6)
C40.6240 (3)0.1354 (3)0.33987 (18)0.0562 (6)
C50.4943 (4)0.0713 (3)0.3353 (2)0.0790 (9)
H5A0.41670.12820.28740.118*
H5B0.43570.06360.40620.118*
H5C0.5472−0.01910.30960.118*
C60.8868 (3)0.1864 (2)0.51606 (17)0.0509 (6)
C70.9984 (3)0.2585 (3)0.50346 (18)0.0554 (6)
H7A1.01830.30540.43740.067*
C81.0807 (3)0.2614 (2)0.58894 (17)0.0529 (6)
C91.0521 (3)0.1928 (2)0.68921 (17)0.0494 (5)
C100.9425 (3)0.1192 (2)0.70122 (17)0.0539 (6)
H10A0.92300.07140.76690.065*
C110.8622 (3)0.1166 (3)0.61544 (18)0.0555 (6)
H11A0.78920.06640.62470.067*
C121.1917 (4)0.3398 (3)0.57499 (19)0.0705 (8)
C131.1139 (3)0.1363 (3)0.87244 (17)0.0532 (6)
H13A1.14890.03710.86770.064*
H13B0.99710.16840.90250.064*
C141.2185 (3)0.1690 (3)0.94322 (18)0.0555 (6)
H14A1.33410.14320.90810.067*
C151.1568 (4)0.3222 (3)0.9600 (2)0.0716 (7)
H15A1.16030.37440.89140.107*
H15B1.22700.34041.00390.107*
H15C1.04400.34870.99520.107*
C161.2148 (4)0.0832 (4)1.0511 (2)0.0829 (9)
H16A1.2555−0.01341.03890.124*
H16B1.10210.10771.08650.124*
H16C1.28440.10121.09560.124*
N30.6706 (3)0.3879 (3)0.89010 (17)0.0662 (6)
C170.5872 (4)0.4524 (3)0.6832 (2)0.0784 (9)
H17A0.55890.47420.61340.094*
C180.6965 (4)0.5024 (3)0.7160 (2)0.0755 (8)
H18A0.74440.55890.66870.091*
C190.7359 (4)0.4686 (3)0.8200 (2)0.0702 (7)
H19A0.81060.50350.84180.084*
C200.5646 (3)0.3398 (3)0.8567 (2)0.0743 (8)
H20A0.51820.28300.90480.089*
C210.5200 (4)0.3700 (4)0.7544 (2)0.0816 (9)
H21A0.44470.33450.73410.098*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S0.0649 (4)0.0694 (4)0.0399 (3)−0.0261 (3)−0.0190 (3)0.0038 (3)
O10.0859 (13)0.1005 (15)0.0542 (11)−0.0423 (11)−0.0318 (9)0.0028 (10)
O20.0786 (12)0.1131 (16)0.0442 (9)−0.0428 (12)−0.0256 (9)0.0128 (10)
O30.0751 (11)0.0709 (11)0.0383 (8)−0.0323 (9)−0.0229 (7)0.0072 (7)
N10.0607 (12)0.0784 (14)0.0422 (10)−0.0284 (11)−0.0138 (9)−0.0006 (9)
N20.148 (3)0.140 (3)0.0683 (16)−0.102 (2)−0.0507 (17)0.0359 (16)
C10.0562 (14)0.0680 (16)0.0436 (12)−0.0115 (12)−0.0179 (11)−0.0042 (11)
C20.0498 (13)0.0645 (15)0.0428 (12)−0.0140 (11)−0.0157 (10)−0.0078 (10)
C30.0547 (13)0.0588 (14)0.0387 (12)−0.0158 (11)−0.0124 (10)−0.0011 (10)
C40.0553 (14)0.0725 (16)0.0445 (12)−0.0224 (12)−0.0131 (10)−0.0058 (11)
C50.0804 (19)0.113 (2)0.0605 (16)−0.0508 (18)−0.0194 (14)−0.0009 (16)
C60.0562 (13)0.0583 (14)0.0383 (11)−0.0164 (11)−0.0130 (10)−0.0027 (10)
C70.0665 (15)0.0631 (15)0.0382 (11)−0.0226 (12)−0.0155 (10)0.0049 (10)
C80.0653 (15)0.0591 (14)0.0391 (12)−0.0249 (12)−0.0163 (10)0.0034 (10)
C90.0599 (13)0.0503 (13)0.0378 (11)−0.0152 (11)−0.0148 (10)−0.0015 (9)
C100.0697 (15)0.0583 (14)0.0362 (11)−0.0240 (12)−0.0147 (10)0.0053 (10)
C110.0658 (15)0.0625 (15)0.0448 (12)−0.0273 (12)−0.0150 (10)−0.0011 (10)
C120.095 (2)0.089 (2)0.0439 (13)−0.0501 (17)−0.0309 (13)0.0172 (13)
C130.0673 (15)0.0578 (14)0.0367 (11)−0.0214 (12)−0.0164 (10)0.0025 (10)
C140.0565 (14)0.0710 (16)0.0400 (12)−0.0198 (12)−0.0142 (10)−0.0021 (11)
C150.0767 (18)0.084 (2)0.0662 (16)−0.0361 (15)−0.0154 (14)−0.0125 (14)
C160.104 (2)0.103 (2)0.0470 (14)−0.0364 (19)−0.0328 (15)0.0091 (14)
N30.0607 (13)0.0864 (16)0.0445 (11)−0.0141 (12)−0.0165 (10)0.0022 (10)
C170.0798 (19)0.094 (2)0.0447 (14)−0.0046 (17)−0.0231 (13)0.0020 (14)
C180.085 (2)0.0775 (19)0.0538 (15)−0.0176 (16)−0.0115 (14)0.0084 (13)
C190.0737 (17)0.0765 (18)0.0588 (16)−0.0207 (15)−0.0166 (13)−0.0022 (13)
C200.0643 (17)0.104 (2)0.0547 (15)−0.0288 (16)−0.0183 (13)0.0081 (14)
C210.0717 (18)0.118 (3)0.0588 (16)−0.0306 (17)−0.0282 (14)0.0032 (16)
Geometric parameters (Å, º) top
S—C21.714 (2)C10—H10A0.93
S—C31.718 (2)C11—H11A0.93
O1—C11.214 (3)C13—C141.508 (3)
O2—C11.304 (3)C13—H13A0.97
O2—H2A0.82C13—H13B0.97
O3—C91.352 (3)C14—C151.516 (4)
O3—C131.442 (3)C14—C161.526 (4)
N1—C31.310 (3)C14—H14A0.98
N1—C41.367 (3)C15—H15A0.96
N2—C121.143 (4)C15—H15B0.96
C1—C21.485 (3)C15—H15C0.96
C2—C41.369 (4)C16—H16A0.96
C3—C61.472 (3)C16—H16B0.96
C4—C51.494 (3)C16—H16C0.96
C5—H5A0.96N3—C201.323 (4)
C5—H5B0.96N3—C191.330 (4)
C5—H5C0.96C17—C181.357 (4)
C6—C111.386 (3)C17—C211.357 (5)
C6—C71.386 (3)C17—H17A0.93
C7—C81.391 (3)C18—C191.377 (4)
C7—H7A0.93C18—H18A0.93
C8—C91.396 (3)C19—H19A0.93
C8—C121.432 (4)C20—C211.371 (4)
C9—C101.384 (3)C20—H20A0.93
C10—C111.382 (3)C21—H21A0.93
C2—S—C389.34 (11)O3—C13—C14107.94 (19)
C1—O2—H2A109.5O3—C13—H13A110.1
C9—O3—C13118.94 (18)C14—C13—H13A110.1
C3—N1—C4111.2 (2)O3—C13—H13B110.1
O1—C1—O2124.6 (2)C14—C13—H13B110.1
O1—C1—C2123.2 (3)H13A—C13—H13B108.4
O2—C1—C2112.2 (2)C13—C14—C15111.3 (2)
C4—C2—C1129.7 (2)C13—C14—C16109.1 (2)
C4—C2—S110.16 (17)C15—C14—C16110.7 (2)
C1—C2—S120.2 (2)C13—C14—H14A108.6
N1—C3—C6123.1 (2)C15—C14—H14A108.6
N1—C3—S114.60 (16)C16—C14—H14A108.6
C6—C3—S122.33 (18)C14—C15—H15A109.5
N1—C4—C2114.7 (2)C14—C15—H15B109.5
N1—C4—C5118.6 (2)H15A—C15—H15B109.5
C2—C4—C5126.7 (2)C14—C15—H15C109.5
C4—C5—H5A109.5H15A—C15—H15C109.5
C4—C5—H5B109.5H15B—C15—H15C109.5
H5A—C5—H5B109.5C14—C16—H16A109.5
C4—C5—H5C109.5C14—C16—H16B109.5
H5A—C5—H5C109.5H16A—C16—H16B109.5
H5B—C5—H5C109.5C14—C16—H16C109.5
C11—C6—C7117.9 (2)H16A—C16—H16C109.5
C11—C6—C3121.4 (2)H16B—C16—H16C109.5
C7—C6—C3120.7 (2)C20—N3—C19117.5 (2)
C6—C7—C8120.5 (2)C18—C17—C21118.6 (3)
C6—C7—H7A119.8C18—C17—H17A120.7
C8—C7—H7A119.8C21—C17—H17A120.7
C7—C8—C9120.9 (2)C17—C18—C19119.4 (3)
C7—C8—C12119.5 (2)C17—C18—H18A120.3
C9—C8—C12119.6 (2)C19—C18—H18A120.3
O3—C9—C10125.7 (2)N3—C19—C18122.2 (3)
O3—C9—C8115.8 (2)N3—C19—H19A118.9
C10—C9—C8118.6 (2)C18—C19—H19A118.9
C11—C10—C9119.9 (2)N3—C20—C21123.0 (3)
C11—C10—H10A120.0N3—C20—H20A118.5
C9—C10—H10A120.0C21—C20—H20A118.5
C10—C11—C6122.2 (2)C17—C21—C20119.2 (3)
C10—C11—H11A118.9C17—C21—H21A120.4
C6—C11—H11A118.9C20—C21—H21A120.4
N2—C12—C8178.1 (3)
O1—C1—C2—C4−0.7 (4)C6—C7—C8—C9−0.4 (4)
O2—C1—C2—C4179.4 (2)C6—C7—C8—C12−178.2 (2)
O1—C1—C2—S−179.5 (2)C13—O3—C9—C100.5 (3)
O2—C1—C2—S0.6 (3)C13—O3—C9—C8−179.5 (2)
C3—S—C2—C40.17 (19)C7—C8—C9—O3−178.6 (2)
C3—S—C2—C1179.2 (2)C12—C8—C9—O3−0.8 (4)
C4—N1—C3—C6−179.6 (2)C7—C8—C9—C101.4 (4)
C4—N1—C3—S0.1 (3)C12—C8—C9—C10179.1 (2)
C2—S—C3—N1−0.1 (2)O3—C9—C10—C11178.9 (2)
C2—S—C3—C6179.5 (2)C8—C9—C10—C11−1.0 (3)
C3—N1—C4—C20.1 (3)C9—C10—C11—C6−0.2 (4)
C3—N1—C4—C5−179.3 (2)C7—C6—C11—C101.1 (4)
C1—C2—C4—N1−179.0 (2)C3—C6—C11—C10−178.8 (2)
S—C2—C4—N1−0.2 (3)C9—O3—C13—C14−179.00 (19)
C1—C2—C4—C50.3 (4)O3—C13—C14—C1564.7 (3)
S—C2—C4—C5179.2 (2)O3—C13—C14—C16−173.0 (2)
N1—C3—C6—C112.2 (4)C21—C17—C18—C19−0.1 (5)
S—C3—C6—C11−177.39 (18)C20—N3—C19—C180.0 (4)
N1—C3—C6—C7−177.7 (2)C17—C18—C19—N30.2 (4)
S—C3—C6—C72.7 (3)C19—N3—C20—C21−0.2 (4)
C11—C6—C7—C8−0.8 (4)C18—C17—C21—C20−0.1 (5)
C3—C6—C7—C8179.1 (2)N3—C20—C21—C170.2 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2A···N3i0.821.792.611 (3)174
C5—H5A···O10.962.523.055 (3)115
Symmetry code: (i) x, y, z−1.

Experimental details

Crystal data
Chemical formulaC16H16N2O3S·C5H5N
Mr395.47
Crystal system, space groupTriclinic, P1
Temperature (K)296
a, b, c (Å)8.6040 (17), 10.339 (2), 12.611 (3)
α, β, γ (°)82.51 (3), 80.69 (3), 69.61 (3)
V (Å3)1034.4 (4)
Z2
Radiation typeMo Kα
µ (mm−1)0.18
Crystal size (mm)0.30 × 0.20 × 0.20
Data collection
DiffractometerEnraf–Nonius CAD-4
Absorption correctionψ scan
(North et al., 1968)
Tmin, Tmax0.947, 0.964
No. of measured, independent and
observed [I > 2σ(I)] reflections		4017, 3747, 2815
Rint0.032
(sin θ/λ)max (Å−1)0.601
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.156, 0.99
No. of reflections3747
No. of parameters255
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.33, −0.19

Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1994), XCAD4 (Harms & Wocadlo,1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2A···N3i0.821.792.611 (3)174
Symmetry code: (i) x, y, z−1.
 

References

First citationAlexander, S. (2008). Arthritis Res. Ther. 10, 221–227.  Web of Science PubMed Google Scholar
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 First citationEnraf–Nonius (1994). CAD-4 EXPRESS. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
 First citationFontrodona, X., Diaz, S., Linden, A. & Villalgordo, J. M. (2001). Synthesis, pp. 2021–2027.  CSD CrossRef Google Scholar
 First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.  Google Scholar
 First citationHiramatsu, T., Matsumoto, K. & Watanabe, K. (2000). China Patent CN1 275 126.  Google Scholar
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 First citationPerez-Ruiz, F., Dalbeth, N. & Schlesinger, N. (2008). Future Rheumatol. 3, 421–427.  CrossRef CAS Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSorbera, L. A., Revel, L., Rabasseda, X. & Castaner, J. (2001). Drugs Fut. 26, 32–38.  CAS Google Scholar
 First citationZhou, X. G., Tang, X. M., Deng, J., Ye, W. R., Luo, J., Luo, J., Zhang, D. L. & Fan, B. (2007). China Patent CN1 970 547.  Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

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ISSN: 2056-9890
Volume 65| Part 11| November 2009| Page o2603
https://doi.org/10.1107/S1600536809039002
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