Ethyl 7-(2-chloro­phen­yl)-5-trifluoro­meth­yl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxyl­ate

Jie Mou; Chen-Xia Yu; Chang-Sheng Yao

doi:10.1107/S1600536810037712

. 2010 Sep 25;66(Pt 10):o2642. doi: 10.1107/S1600536810037712

Ethyl 7-(2-chlorophenyl)-5-trifluoromethyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylate

Jie Mou ^a, Chen-Xia Yu ^b,^c, Chang-Sheng Yao ^b,^c,^*

PMCID: PMC2983298 PMID: 21587613

Abstract

In the title compound, C₁₅H₁₂ClF₃N₄O₂, the dihydropyrimidine ring exhibits an envelope conformation. The dihedral angle between the mean planes of the dihydropyrimidine and phenyl rings is 83.94 (6)°. The OCH₂CH₃ group is disordered over two sites with occupancies of 0.155 (3) and 0.845 (3). The crystal packing is stabilized by intermolecular N—H⋯N hydrogen bonds.

Related literature

For the anticancer activity, inhibition of the MDM2-p53 protein–protein interaction and the antituberculosis and dehydrogenase inhibitory activity of [1,2,4]triazolo [1,5-a]pyrimidine derivatives, see: Zhang et al. (2007 ▶); Allen et al. (2009 ▶); Pereyaslavskaya et al. (2008 ▶); Gujjar et al. (2009 ▶). For the bioactivity of trifluoromethylated molecules, see: Kirk, (2006 ▶). For the preparation of trifluoromethylated [1,2,4]triazolo[1,5-a]pyrimidine derivatives, see Pryadeina et al. (2004 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₅H₁₂ClF₃N₄O₂
M _r = 372.74
Monoclinic,
a = 9.8927 (12) Å
b = 6.8055 (6) Å
c = 24.403 (3) Å
β = 99.237 (9)°
V = 1621.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.29 mm⁻¹
T = 113 K
0.26 × 0.22 × 0.20 mm

Data collection

Rigaku Saturn diffractometer
Absorption correction: multi-scan (CrystalClear;Rigaku/MSC, 2002 ▶) T _min = 0.930, T _max = 0.945
14364 measured reflections
3835 independent reflections
3058 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.121
S = 1.08
3835 reflections
242 parameters
6 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.40 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2002 ▶); 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 I, global. DOI: 10.1107/S1600536810037712/hg2715sup1.cif

e-66-o2642-sup1.cif^{(21.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810037712/hg2715Isup2.hkl

e-66-o2642-Isup2.hkl^{(188KB, 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
N1—H1⋯N4ⁱ	0.90 (2)	1.96 (2)	2.843 (2)	166.3 (19)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by the Special Fund for the President’s Project (Project 2009 KJZ20) of Xuzhou Medical College.

supplementary crystallographic information

Comment

1,2,4-Triazolo[1,5-a]pyrimidine derivatives are known because of their wide range of biological activities. For example, some of the trizaolopyrimidines can be used as anticancer agents (Zhang et al., 2007), inhibitor of the MDM2-p53 protein-protein interaction (Allen et al., 2009), antituberculosis agents (Pereyaslavskaya et al., 2008) and dehydrogenase inhibitors (Gujjar et al., 2009). Therefore, the preparation or structural modification of these nitrogen-containing heterocyclic scaffolds is of considerable interest for both organic and medicinal chemistry. The introduction of a trifluoromethyl group into organic molecules often changes their physical, chemical, and physiological properties (Kirk, 2006). During the synthesis of trifluoromethylated 1,2,4-Triazolo[1,5-a]pyrimidine derivatives, the title compound (I) was isolated and its structure was determined by X-ray analysis. The results are presented here.

In the title molecule (Fig. 1), the 1,2,4-triazole ring adopts a planar conformation. Cremer & Pople puckering analysis (Cremer &Pople, 1975) can not be performed, for its weighted average absolute torsion angle is 0.7°, less than 5.0°. The dihydropyrimidine ring system is in an envelope conformation, for Cremer & Pople puckering analysis shows θ(2) and φ(2) are 0.094 (2)Å and 346.4 (10)°, respectively. Its puckering amplitude (Q) is 0.099 (2)Å. Besides, the distance between atom C2 and the mean N2/C1/N1/C4/C3 plane (r.m.s. deviation 0.016 Å) is 0.136 (2) Å, which also confirms the conformation of the dihydropyrimidine ring. The dihedral angle between the aforementioned weighted plane and phenyl ring is 83.94 (6)°, which shows the two units are nearly perpendicular.

The crystal packing is stabilized by intermolecular N—H···N hydrogen bonds (Table 1, Fig.2).

Experimental

The title compound was synthesized according the procedure reported by Pryadeina et al. (2004). A mixture of 0.01 mol of ethyl 4,4,4-trifluoro-3-oxobutanoate, 0.01 mol of 2-chlorobenzaldehyde and 0.01 mol of 1H-1,2,4-triazol-5-amine in 20 mL of ethanol containing a catalytic amount of hydrochloric acid was heated for 12 h under reflux. Then the solvent was removed under reduced pressure. The residue was added to a solution of p-toluenesulfonic acid, 0.05 g, in 100 mL of benzene, and the mixture was heated for 8 h with simultaneous removal of water as azeotrope with benzene. The solution was filtered while hot, the filtrate was evaporated, and the precipitate was recrystallized from ethanol. Cooling the ethanol solution slowly gave single crystals suitable for X-ray diffraction.