N-Methyl-4-(4-pivalamido­phenyl­sulfan­yl)picolinamide hemihydrate

Ting-Hong Ye; Ting-Ting Huang; Yao-Jie Shi; Ying Xiong; Luo-Ting Yu

doi:10.1107/S1600536811012268

. 2011 Apr 13;67(Pt 5):o1098. doi: 10.1107/S1600536811012268

N-Methyl-4-(4-pivalamidophenylsulfanyl)picolinamide hemihydrate

Ting-Hong Ye ^a, Ting-Ting Huang ^a, Yao-Jie Shi ^a, Ying Xiong ^b, Luo-Ting Yu ^a,^*

PMCID: PMC3089303 PMID: 21754418

Abstract

In the title compound, C₁₈H₂₁N₃O₂S·0.5H₂O, the benzene ring makes dihedral angles of 88.59 (6) and 40.74 (8)° with the pyridine ring and the amide group, respectively. The water O atom lies on a twofold axis. In the crystal, the organic molecules and the water molecules are linked via O—H⋯O hydrogen bonds, while the organic molecules are connected to each other via N—H⋯O hydrogen bonds, forming a three-dimensional network.

Related literature

For related compounds and their biological activity, see: Khire et al. (2004 ▶); Dominguez et al. (2007 ▶).

Experimental

Crystal data

C₁₈H₂₁N₃O₂S·0.5H₂O
M _r = 352.46
Monoclinic,
a = 12.7413 (4) Å
b = 17.5056 (8) Å
c = 17.1978 (6) Å
β = 108.632 (4)°
V = 3634.8 (2) Å³
Z = 8
Mo Kα radiation
μ = 0.20 mm⁻¹
T = 293 K
0.24 × 0.22 × 0.18 mm

Data collection

Oxford Diffraction Xcalibur Eos diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2010 ▶) T _min = 0.966, T _max = 1.000
3714 measured reflections
3714 independent reflections
2498 reflections with I > 2σ(I)

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.111
S = 0.96
3714 reflections
238 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: OLEX2.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811012268/zq2092sup1.cif

e-67-o1098-sup1.cif^{(20.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811012268/zq2092Isup2.hkl

e-67-o1098-Isup2.hkl^{(182.2KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3A⋯O1ⁱ	0.854 (18)	2.335 (18)	3.0317 (19)	139.0 (15)
O3—H3⋯O2ⁱⁱ	0.87 (2)	1.94 (2)	2.8059 (18)	174.2
N1—H1⋯O3	0.850 (19)	2.269 (19)	3.089 (2)	162.3 (18)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We thank the Analytical and Testing Center of Sichuan University for the X-ray measurements.

supplementary crystallographic information

Comment

Sorafenib is a molecule of great importance owing to its antitumor properties (Khire et al., 2004; Dominguez et al., 2007). The title compound, which is one of its derivatives, possesses even better in vitro anticancer activity against both two tumor cell lines (HCT116 and HEPG2). As a potent antitumor drug, we report here its crystal structure.

In the title molecule, C₁₈H₂₁N₃O₂S.0.5(H₂O), the central benzene ring makes dihedral angles of 88.59 (6)° and 40.74 (8)° with the pyridine and amide bonds, respectively (Fig. 1). The O atom of the isolated water molecule lies on a two-fold axis. In the crystal structure, two organic molecules and one water molecule are linked via the O3—H3···O2ⁱⁱ hydrogen bonds, while organic molecules are connected with each other via the N3—H3A···O1ⁱ hydrogen bonds, forming a three-dimensional network [symmetry codes: (i) x-1, y, z; (ii) x+3/2, y+3/2, z+1.Table 1 and Fig. 2].

Experimental

To the suspension of anhydrous potassium carbonate (0.69 g, 5.0 mmol) and 4-(4-aminophenylthio)-N-methylpicolinamide (0.52 g, 2.0 mmol) in 7.0 ml THF was added dropwise pivaloyl chloride (0.25 g, 2.1 mmol). After being stirred at room temperature for 2 h, the mixture was extracted with 30 ml EA and 30 ml brine for three times and the combined organic layers were dried over anhydrous sodium sulfate. Then the solution was concentrated under vacuum, and the residue was recrystallized from ethanol to give the title compound, with 40% yield. Crystals suitable for a X-ray analysis were obtained by slow evaporation from a solution of ethanol at room temperature.