7-Chloro-11a-phenyl-2,3,5,10,11,11a-hexa­hydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione

Rafael Tamazyan; Armen Ayvazyan; Ashot Martirosyan; Gohar Harutyunyan; Vahan Martirosyan

doi:10.1107/S160053680800408X

. 2008 Feb 13;64(Pt 3):o587. doi: 10.1107/S160053680800408X

7-Chloro-11a-phenyl-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione

Rafael Tamazyan ^a,^*, Armen Ayvazyan ^a, Ashot Martirosyan ^b, Gohar Harutyunyan ^b, Vahan Martirosyan ^b

PMCID: PMC2960833 PMID: 21201925

Abstract

The title compound, C₁₈H₁₅ClN₂O₂, is a potential human immunodeficiency virus type-1 (HIV-1) non-nucleoside reverse transcriptase inhibitor. The pyrrolidine ring adopts an envelope and the diazepine ring a boat conformation. In the crystal structure, two isomers (R and S) form centrosymmetric dimers via N—H⋯O hydrogen bonds.

Related literature

For details of the pharmacological properties of this family of compounds, see: De Clercq (1996 ▶). For the crystal structures of some analogues of the title compound, see: Karapetyan et al. (2002 ▶); Tamazyan et al. (2002 ▶, 2007 ▶). For reference structural data, see Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₈H₁₅ClN₂O₂
M _r = 326.77
Triclinic,
a = 8.9749 (18) Å
b = 9.2184 (18) Å
c = 9.912 (2) Å
α = 86.90 (3)°
β = 71.35 (3)°
γ = 88.27 (3)°
V = 775.8 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 293 (2) K
0.35 × 0.32 × 0.28 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
7347 measured reflections
4514 independent reflections
3148 reflections with I > 2σ(I)
R _int = 0.035
3 standard reflections frequency: 180 min intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.121
S = 1.02
4514 reflections
268 parameters
All H-atom parameters refined
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.31 e Å⁻³

Data collection: DATCOL in CAD-4 (Enraf–Nonius, 1988 ▶); cell refinement: LS in CAD-4; data reduction: HELENA (Spek, 1997 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶) and ORTEPII (Johnson, 1976 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680800408X/sj2462sup1.cif

e-64-0o587-sup1.cif^{(20.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680800408X/sj2462Isup2.hkl

e-64-0o587-Isup2.hkl^{(221.1KB, 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
N4—H4⋯O12ⁱ	0.85 (2)	2.35 (2)	2.997 (2)	133 (2)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This research was carried out under the framework of the Armenian Science and Education Foundation (ANSEF grant No. PS-chemorg-907). The authors express their thanks to ANSEF.

supplementary crystallographic information

Comment

Interest in X-ray structural investigation of title compound, (I), Fig. 1, is stimulated by its potentially HIV-1 RT inhibition properties. These compounds belong to a family of non-nucleoside reverse transcriptase inhibitors (NNRTIs).

All intramolecular interatomic distances in molecule are in good agreement with their mean statistical values (Allen et al., 1987). In the crystal structure dimers are formed by (R and S) optical isomers of molecules of (I) via O12···H4ⁱ—N4ⁱ and O12ⁱ···H4—N4 double hydrogen bonding (Table 1, Fig.2).

Experimental

A solution of 2-phenyl-2-pyrrolidinecarboxylic acid (0.01 mol) and 6-chloro-1,4-dihydro-2H-3,1-benzoxazine-2,4-dione (0.01 mol) in dry DMF (5 ml) was boiled for 4 h. After cooling in an ice bath the title compound formed as a colourless precipitate and was separated by filtration and washed with ethylacetate. The compound as synthesized was a racemic mixture. Crystals were grown from an ethanol solution of the compound.