1-Benzyl-2-(1H-indol-3-yl)-5-oxo­pyrrolidine-2-carbonitrile

Rafael Tamazyan; Ayvazyan Armen; Martirosyan Ashot; Gasparyan Sahak; Raymond Schinazi

doi:10.1107/S1600536807067670

. 2008 Jan 4;64(Pt 2):o368. doi: 10.1107/S1600536807067670

1-Benzyl-2-(1H-indol-3-yl)-5-oxopyrrolidine-2-carbonitrile

Rafael Tamazyan ^a,^*, Ayvazyan Armen ^a, Martirosyan Ashot ^b, Gasparyan Sahak ^b, Raymond Schinazi ^c

PMCID: PMC2960201 PMID: 21201400

Abstract

In the title compound, C₂₀H₁₇N₃O, a potential anti-human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse-transcriptase inhibitor, the pyrrolidine ring has an envelope conformation. In the crystal structure, adjacent molecules are connected into infinite chains via an N—H⋯O hydrogen bond.

Related literature

For details of the synthesis, see: Martirosyan et al. (2000 ▶, 2004 ▶). For details of the pharmacological properties of compounds of this family, see: De Clercq (1996 ▶). For the crystal structures of some analogs of the title compound, see: Karapetyan et al. (2002 ▶); Tamazyan et al. (2002 ▶).

Experimental

Crystal data

C₂₀H₁₇N₃O
M _r = 315.37
Triclinic,
a = 7.5781 (15) Å
b = 9.4521 (19) Å
c = 12.409 (3) Å
α = 78.02 (3)°
β = 83.05 (3)°
γ = 69.68 (3)°
V = 814.2 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 (2) K
0.4 × 0.3 × 0.2 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
9470 measured reflections
4735 independent reflections
3450 reflections with I > 2σ(I)
R _int = 0.020
3 standard reflections frequency: 180 min intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.130
S = 1.02
4735 reflections
285 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CAD-4 Manual (Enraf–Nonius, 1988 ▶); cell refinement: CAD-4 Manual; data reduction: HELENA (Spek, 1997 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ▶); molecular graphics: SHELXTL (Bruker 2000 ▶) and ORTEPII (Johnson, 1976 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536807067670/su2039sup1.cif

e-64-0o368-sup1.cif^{(18KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807067670/su2039Isup2.hkl

e-64-0o368-Isup2.hkl^{(231.9KB, 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
N11—H11⋯O6ⁱ	0.90 (2)	2.01 (2)	2.866 (2)	158 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

We are grateful to the Civilian Research and Development Foundation (CRDF), USA, for financial support (grant No. ARB2–2701-YE-05).

supplementary crystallographic information

Comment

Our interest in the X-ray structural investigation of the title compound was stimulated by its potential HIV-1 RT inhibition properties. Compounds of this type belong to family of non-nucleoside reverse transcriptase inhibitors (NNRTIs).

A view of the molecular structure of the title compound is given in Fig. 1. A l l the bond distances in the molecule are in good agreement with their mean statistical values, except bond C2—C7 which is relatively short, 1.493 (2) Å. We believe that this shortening is caused by the inductive effect of the carbonitryl group C7 ≡N11.

In the crystal structure infinite chains along [010] direction are formed via an intermolecular N—H···O hydrogen bond (see Fig. 2 and Table 1).

Experimental

The title compound was synthesized by the cycloalkylation of N1-benzyl-N1-cyano(1H-3-indolyl)methyl-3-chloropropanamide in the phase-transfer catalysis condition (Martirosyan et al., 2000, 2004). The compound as synthesized is a racemic mixture. Colorless crystals, suitable for X-ray analysis, were grown from a methanol solution of the compound.