N-(2-Chloro­pyrimidin-4-yl)-N,2-di­methyl-2H-indazol-6-amine

Hao-Fei Qi; Bing-Ni Liu; Mo Liu; Deng-Ke Liu

doi:10.1107/S1600536810042753

. 2010 Oct 30;66(Pt 11):o2955. doi: 10.1107/S1600536810042753

N-(2-Chloropyrimidin-4-yl)-N,2-dimethyl-2H-indazol-6-amine

Hao-Fei Qi ^a, Bing-Ni Liu ^b,^*, Mo Liu ^b, Deng-Ke Liu ^b

PMCID: PMC3009102 PMID: 21589123

Abstract

In the title compound, C₁₃H₁₂ClN₅, which is a derivative of the antitumor agent pazopanib {systematic name: 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzolsulfonamide}, the indazole and pyrimidine fragments form a dihedral angle of 62.63 (5)°. In the crystal, pairs of molecules related by twofold rotational symmetry are linked into dimers through π–π interactions between the indazole ring systems [centroid–centroid distance = 3.720 (2) Å]. Weak intermolecular C—H⋯N hydrogen bonds further assemble these dimers into columns propagated in [001].

Related literature

For background to the pharmacokinetics and clinical studies of the antitumor agent pazopanib, see: Limvorasak & Posadas (2009 ▶); Sloan & Scheinfeld 2008 ▶; Sonpavde et al. (2007 ▶). For the synthesis of pazopanib, see: Sorbera et al. (2006 ▶).

Experimental

Crystal data

C₁₃H₁₂ClN₅
M _r = 273.73
Monoclinic,
a = 21.432 (4) Å
b = 9.836 (2) Å
c = 12.542 (3) Å
β = 90.25 (3)°
V = 2644.1 (9) Å³
Z = 8
Mo Kα radiation
μ = 0.28 mm⁻¹
T = 113 K
0.20 × 0.18 × 0.12 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 ▶) T _min = 0.946, T _max = 0.967
10576 measured reflections
2323 independent reflections
1982 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.100
S = 1.01
2323 reflections
175 parameters
H-atom parameters constrained
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; 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: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810042753/cv2775sup1.cif

e-66-o2955-sup1.cif^{(18.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810042753/cv2775Isup2.hkl

e-66-o2955-Isup2.hkl^{(114.3KB, 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
C13—H13B⋯N2ⁱ	0.98	2.56	3.517 (2)	166

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank Mr Hai-Bin Song of Nankai University and Mr Shuai Mu of Tianjin University for their helpful suggestions.

supplementary crystallographic information

Comment

Pazopanib is an oral, second-generation multi-targeted tyrosine kinase inhibitor that targets VEGFR, platelet-derived growth factor receptor and c-kit, key proteins responsible for tumor growth and survival (Limvorasak et al., 2009; Sloan et al., 2008; Sonpavde et al., 2007). The crystal structure of the title compound (I), a derivative of pazopanib, synthesized through the transformation of pazopanib (Sorbera et al., 2006), is reported here.

In (I) (Fig. 1), the indazole and pyrimidine fragments form a dihedral angle of 62.63 (5)°. In the crystal structure, The π–π contacts between the indazole systems from the adjacent molecules (Table 1) link them into dimers. Weak intermolecular C—H···N hydrogen bonds (Table 2) link further the dimers into columns propagated in direction [001].

Experimental

To a stirred solution of the N-(2-chloropyrimidin-4-yl)-2 -methyl-2H-indazol-6-amine 5 g (0.02 mol) in DMF (30 ml) was added Cs₂CO₃ 9.8 g (0.03 mol) and iodomethane 2.5 ml (5.7 g, 0.04 mol) at room temperature. The mixture was stirred for 5 h. The reaction mixture was then poured into an ice-water bath, and the precipitate was collected via filtration and washed with water. The precipitate was air-dried to get off-white solid as crude product. The solid was dissolved in ethyl acetate 30 ml at 278 k, then white crystals were generated slowly.