6-Cyclo­hexyl­meth­yl-5-ethyl-2-[(2-oxo-2-phenyl­eth­yl)sulfan­yl]pyrimidin-4(3H)-one

Wan-Lu Yan; Qiong Guo; Cong Li; Xiao-Ying Ji; Yan-Ping He

doi:10.1107/S1600536811003175

. 2011 Jan 29;67(Pt 2):o534. doi: 10.1107/S1600536811003175

6-Cyclohexylmethyl-5-ethyl-2-[(2-oxo-2-phenylethyl)sulfanyl]pyrimidin-4(3H)-one

Wan-Lu Yan ^a, Qiong Guo ^a, Cong Li ^a, Xiao-Ying Ji ^b, Yan-Ping He ^a,^*

PMCID: PMC3051611 PMID: 21523182

Abstract

In the title compound, C₂₁H₂₆N₂O₂S, the cyclohexane ring adopts a chair conformation. The angle at the methylene bridge linking the pyrimidine and cyclohexane rings is 113.41 (13)°. This is in the range considered optimal for maximum activity of non-nucleoside reverse transcriptase inhibitors. In the crystal, molecules are connected into centrosymmetric dimers via pairs of N—H⋯O hydrogen bonds.

Related literature

For the biological activity of 2-alkylsulfanyl-6-benzyl-3,4-dihydropyrimidin-4(3H)-one derivatives, which show remarkable anti-HIV-1 activity, see: He et al. (2011 ▶); Ettorre et al. (1996 ▶). For related structures, see: Ettorre et al. (1998 ▶); Rao et al. (2007 ▶); Zhang et al. (2008 ▶).

Experimental

Crystal data

C₂₁H₂₆N₂O₂S
M _r = 370.50
Triclinic,
a = 7.516 (5) Å
b = 10.960 (5) Å
c = 12.490 (5) Å
α = 84.082 (5)°
β = 78.925 (5)°
γ = 80.267 (5)°
V = 992.5 (9) Å³
Z = 2
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 293 K
0.46 × 0.23 × 0.17 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.944, T _max = 0.975
7097 measured reflections
4158 independent reflections
3203 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.129
S = 1.03
4158 reflections
237 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: SMART (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; 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/S1600536811003175/tk2710sup1.cif

e-67-0o534-sup1.cif^{(22.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811003175/tk2710Isup2.hkl

e-67-0o534-Isup2.hkl^{(203.7KB, 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
N2—H2A⋯O2ⁱ	0.86	1.90	2.743 (2)	168

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant No. 30960459).

supplementary crystallographic information

Comment

As part of on-going investigations of S-DABO analogues, e.g. 2-alkylsulfanyl-6-benzyl-3,4-dihydropyrimidin-4(3H) -one derivatives, which comprise a potent family of non-nucleoside reverse transcriptase inhibitors (NNRTI's), the title compound was synthesized as a novel inhibitor which shows remarkable anti-HIV-1 activity (He et al., 2011).

The molecular structure is shown in Fig. 1. The cyclohexane ring adopts a chair conformation. The C12—C15—C16 angle is 113.41 (13)°, which is in the range considered optimal for maximum activity of NNRTI's, viz. 110–115° (Ettorre et al., 1996).

A comparison of the molecular structure of the title compound with some reported S-DABO's show that their spatial arrangement are similar (Ettorre et al., 1998; Rao et al., 2007; Zhang et al., 2008). Although these molecules assume similar conformations, they show differences in their activities. Thus, further structural investigations are needed in order to establish a structure-activity relationship.

In the crystal, molecules are connected into centrosymmetric dimers via N—H···O hydrogen bonds, Table 1.

Experimental

With 2-cyclohexylacetonitrile as the starting material, the title compound was synthesized according to the procedure of He et al. (2011). Single crystals of the title compound were obtained from the slow evaporation at room temperature of its ethyl acetate/petroleum ether solution.