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Acta Crystallogr Sect E Struct Rep Online. 2008 February 1; 64(Pt 2): o368.
Published online 2008 January 4. doi:  10.1107/S1600536807067670
PMCID: PMC2960201

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

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

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Object name is e-64-0o368-scheme1.jpg

Experimental

Crystal data

  • C20H17N3O
  • M r = 315.37
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o368-efi1.jpg
  • 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
  • Δρmax = 0.18 e Å−3
  • Δρmin = −0.20 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

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

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

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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 [equivalent]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.

Refinement

The H-atoms were located from difference Fourier syntheses and freely refined: N—H = 0.90 (2) Å; C—H = 0.94 (2) - 1.02 (2) Å.

Figures

Fig. 1.
A view of molecular structure of the title compound, showing the atomic numbering scheme and displacement ellipsoids drawn at the 50% probability level. H atoms are omitted for clarity.
Fig. 2.
partial view of the crystal packing showing the formation of the infinite chain of molecules formed via hydrogen bonding [for clarifity only H atoms participating in bonding are depicted]. Symmetry codes: (i) x, 1 + y, z; (ii) x, -1 + y, z.

Crystal data

C20H17N3OZ = 2
Mr = 315.37F000 = 332
Triclinic, P1Dx = 1.286 Mg m3
Hall symbol: -P 1Mo Kα radiation λ = 0.71073 Å
a = 7.5781 (15) ÅCell parameters from 22 reflections
b = 9.4521 (19) Åθ = 14.2–17.5º
c = 12.409 (3) ŵ = 0.08 mm1
α = 78.02 (3)ºT = 293 (2) K
β = 83.05 (3)ºPrism, colourless
γ = 69.68 (3)º0.4 × 0.3 × 0.2 mm
V = 814.2 (3) Å3

Data collection

Enraf–Nonius CAD-4 diffractometerRint = 0.020
Radiation source: fine-focus sealed tubeθmax = 30.0º
Monochromator: graphiteθmin = 1.7º
T = 293(2) Kh = −10→10
θ/2θ scansk = −13→13
Absorption correction: nonel = −17→17
9470 measured reflections3 standard reflections
4735 independent reflections every 180 min
3450 reflections with I > 2σ(I) intensity decay: none

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.047H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.130  w = 1/[σ2(Fo2) + (0.0649P)2 + 0.0907P] where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max < 0.001
4735 reflectionsΔρmax = 0.18 e Å3
285 parametersΔρmin = −0.20 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
N10.22574 (14)0.71961 (10)0.23198 (8)0.0367 (2)
C20.20774 (17)0.64700 (12)0.14116 (9)0.0385 (2)
C30.3119 (3)0.72278 (16)0.04282 (12)0.0552 (4)
H3A0.448 (3)0.655 (2)0.0402 (14)0.066 (5)*
H3B0.258 (2)0.728 (2)−0.0253 (16)0.069 (5)*
C40.2913 (3)0.87637 (17)0.07212 (14)0.0642 (4)
H4A0.182 (3)0.955 (3)0.0430 (19)0.096 (7)*
H4B0.408 (3)0.908 (3)0.049 (2)0.102 (7)*
C50.26566 (17)0.85107 (13)0.19576 (12)0.0453 (3)
O60.27772 (15)0.93414 (11)0.25649 (10)0.0628 (3)
C70.0051 (2)0.69595 (15)0.11645 (11)0.0503 (3)
N8−0.1486 (2)0.73626 (18)0.09409 (14)0.0761 (4)
C90.28897 (17)0.47561 (12)0.16540 (9)0.0379 (2)
C100.2034 (2)0.37431 (15)0.15315 (11)0.0480 (3)
H100.076 (2)0.3968 (19)0.1273 (14)0.063 (5)*
H110.298 (3)0.140 (2)0.1869 (15)0.073 (5)*
N110.32401 (19)0.22756 (13)0.18058 (10)0.0543 (3)
C120.48874 (19)0.23143 (13)0.21285 (10)0.0435 (3)
C130.6498 (2)0.11135 (15)0.24876 (12)0.0574 (4)
H130.655 (2)0.009 (2)0.2546 (15)0.068 (5)*
C140.7955 (2)0.14884 (19)0.27645 (14)0.0656 (4)
H140.911 (3)0.066 (2)0.3034 (16)0.079 (5)*
C150.7826 (2)0.30164 (19)0.26931 (15)0.0641 (4)
H150.887 (3)0.324 (2)0.2894 (16)0.078 (5)*
C160.62465 (19)0.42094 (15)0.23300 (12)0.0498 (3)
H160.620 (2)0.5269 (19)0.2264 (14)0.059 (4)*
C170.47300 (17)0.38670 (12)0.20376 (9)0.0379 (2)
C180.20486 (17)0.65739 (14)0.34923 (10)0.0395 (2)
H18A0.258 (2)0.5459 (17)0.3571 (12)0.047 (4)*
H18B0.280 (2)0.6986 (17)0.3851 (13)0.054 (4)*
C190.00691 (16)0.70242 (13)0.40041 (9)0.0376 (2)
C20−0.1177 (2)0.63319 (19)0.38244 (12)0.0545 (3)
H20−0.077 (2)0.557 (2)0.3324 (15)0.070 (5)*
C21−0.2973 (2)0.6704 (3)0.43232 (14)0.0744 (5)
H21−0.385 (3)0.624 (2)0.4196 (19)0.098 (7)*
C22−0.3538 (3)0.7749 (2)0.50150 (15)0.0782 (6)
H22−0.484 (3)0.800 (2)0.5378 (19)0.099 (7)*
C23−0.2317 (3)0.8426 (2)0.52187 (14)0.0750 (5)
H23−0.264 (3)0.914 (3)0.5704 (19)0.095 (7)*
C24−0.0502 (2)0.80719 (16)0.47138 (11)0.0542 (3)
H240.038 (2)0.858 (2)0.4834 (14)0.065 (5)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0439 (5)0.0279 (4)0.0399 (5)−0.0152 (4)0.0056 (4)−0.0083 (3)
C20.0494 (6)0.0315 (5)0.0350 (5)−0.0157 (5)0.0037 (5)−0.0062 (4)
C30.0742 (10)0.0429 (7)0.0425 (7)−0.0210 (7)0.0150 (7)−0.0026 (5)
C40.0842 (11)0.0384 (7)0.0649 (9)−0.0266 (7)0.0159 (8)0.0017 (6)
C50.0426 (6)0.0272 (5)0.0655 (8)−0.0132 (4)0.0051 (5)−0.0089 (5)
O60.0691 (7)0.0387 (5)0.0905 (8)−0.0253 (5)0.0011 (6)−0.0228 (5)
C70.0609 (8)0.0433 (6)0.0447 (7)−0.0147 (6)−0.0096 (6)−0.0040 (5)
N80.0693 (9)0.0762 (10)0.0782 (10)−0.0154 (7)−0.0267 (8)−0.0059 (8)
C90.0500 (6)0.0304 (5)0.0358 (5)−0.0170 (5)0.0045 (5)−0.0089 (4)
C100.0624 (8)0.0415 (6)0.0490 (7)−0.0263 (6)−0.0024 (6)−0.0121 (5)
N110.0788 (8)0.0341 (5)0.0594 (7)−0.0295 (5)0.0002 (6)−0.0122 (5)
C120.0605 (7)0.0309 (5)0.0390 (6)−0.0180 (5)0.0111 (5)−0.0089 (4)
C130.0738 (10)0.0326 (6)0.0532 (8)−0.0100 (6)0.0146 (7)−0.0041 (5)
C140.0545 (9)0.0536 (8)0.0666 (10)−0.0005 (7)0.0081 (7)0.0005 (7)
C150.0467 (8)0.0635 (9)0.0771 (11)−0.0168 (7)0.0016 (7)−0.0070 (8)
C160.0471 (7)0.0418 (6)0.0622 (8)−0.0188 (5)0.0056 (6)−0.0105 (6)
C170.0475 (6)0.0299 (5)0.0369 (5)−0.0156 (4)0.0097 (5)−0.0095 (4)
C180.0411 (6)0.0387 (6)0.0377 (6)−0.0114 (5)−0.0004 (5)−0.0090 (4)
C190.0429 (6)0.0351 (5)0.0307 (5)−0.0093 (4)0.0006 (4)−0.0049 (4)
C200.0553 (8)0.0719 (9)0.0436 (7)−0.0304 (7)0.0050 (6)−0.0144 (6)
C210.0521 (9)0.1182 (16)0.0534 (9)−0.0380 (10)0.0035 (7)−0.0031 (9)
C220.0529 (9)0.0940 (13)0.0560 (9)−0.0023 (9)0.0154 (7)0.0060 (9)
C230.0899 (13)0.0588 (9)0.0509 (8)0.0010 (9)0.0230 (8)−0.0149 (7)
C240.0726 (9)0.0435 (7)0.0429 (7)−0.0147 (6)0.0073 (6)−0.0138 (5)

Geometric parameters (Å, °)

N1—C51.3542 (15)C13—C141.370 (3)
N1—C181.4634 (16)C13—H130.944 (18)
N1—C21.4775 (15)C14—C151.398 (2)
C2—C71.493 (2)C14—H140.99 (2)
C2—C91.4979 (16)C15—C161.375 (2)
C2—C31.5562 (18)C15—H150.96 (2)
C3—C41.521 (2)C16—C171.4018 (18)
C3—H3A1.009 (18)C16—H160.976 (16)
C3—H3B0.969 (18)C18—C191.5076 (17)
C4—C51.502 (2)C18—H18A0.977 (15)
C4—H4A0.95 (2)C18—H18B0.983 (16)
C4—H4B1.02 (2)C19—C201.3824 (19)
C5—O61.2269 (16)C19—C241.3842 (17)
C7—N81.142 (2)C20—C211.383 (2)
C9—C101.3695 (17)C20—H200.989 (18)
C9—C171.4348 (18)C21—C221.366 (3)
C10—N111.3689 (19)C21—H210.95 (2)
C10—H100.994 (17)C22—C231.365 (3)
N11—C121.3707 (19)C22—H221.00 (2)
N11—H110.90 (2)C23—C241.399 (2)
C12—C131.391 (2)C23—H230.94 (2)
C12—C171.4120 (15)C24—H240.986 (17)
C5—N1—C18122.70 (10)C14—C13—H13122.7 (10)
C5—N1—C2112.91 (10)C12—C13—H13120.0 (10)
C18—N1—C2124.39 (9)C13—C14—C15121.35 (15)
N1—C2—C7109.37 (10)C13—C14—H14119.6 (11)
N1—C2—C9113.04 (10)C15—C14—H14119.1 (11)
C7—C2—C9110.17 (11)C16—C15—C14121.65 (16)
N1—C2—C3101.87 (10)C16—C15—H15118.9 (11)
C7—C2—C3108.24 (12)C14—C15—H15119.4 (11)
C9—C2—C3113.77 (10)C15—C16—C17118.50 (13)
C4—C3—C2104.09 (11)C15—C16—H16120.4 (9)
C4—C3—H3A111.4 (10)C17—C16—H16121.1 (9)
C2—C3—H3A107.7 (10)C16—C17—C12118.72 (12)
C4—C3—H3B115.6 (11)C16—C17—C9134.95 (11)
C2—C3—H3B109.1 (11)C12—C17—C9106.31 (11)
H3A—C3—H3B108.5 (14)N1—C18—C19116.05 (10)
C5—C4—C3104.26 (11)N1—C18—H18A106.8 (9)
C5—C4—H4A108.1 (14)C19—C18—H18A109.9 (8)
C3—C4—H4A112.0 (13)N1—C18—H18B103.9 (9)
C5—C4—H4B109.1 (14)C19—C18—H18B108.7 (9)
C3—C4—H4B112.6 (13)H18A—C18—H18B111.5 (12)
H4A—C4—H4B110.6 (19)C20—C19—C24118.62 (13)
O6—C5—N1124.06 (13)C20—C19—C18120.58 (11)
O6—C5—C4126.73 (12)C24—C19—C18120.70 (12)
N1—C5—C4109.21 (11)C19—C20—C21120.72 (15)
N8—C7—C2177.60 (16)C19—C20—H20118.9 (10)
C10—C9—C17107.09 (11)C21—C20—H20120.3 (10)
C10—C9—C2126.59 (12)C22—C21—C20120.49 (18)
C17—C9—C2126.31 (10)C22—C21—H21118.2 (14)
N11—C10—C9109.47 (13)C20—C21—H21121.3 (14)
N11—C10—H10122.1 (10)C23—C22—C21119.72 (16)
C9—C10—H10128.4 (10)C23—C22—H22120.8 (12)
C10—N11—C12109.29 (11)C21—C22—H22119.5 (12)
C10—N11—H11127.3 (11)C22—C23—C24120.51 (16)
C12—N11—H11122.9 (11)C22—C23—H23122.7 (14)
N11—C12—C13129.75 (12)C24—C23—H23116.8 (14)
N11—C12—C17107.83 (12)C19—C24—C23119.93 (17)
C13—C12—C17122.42 (14)C19—C24—H24118.7 (10)
C14—C13—C12117.34 (13)C23—C24—H24121.3 (10)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N11—H11···O6i0.90 (2)2.01 (2)2.866 (2)158 (2)

Symmetry codes: (i) x, y−1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SU2039).

References

  • Bruker (2000). SHELXTL-NT Version 6.10. Bruker AXS Inc., Madison, Wisconsin, USA.
  • De Clercq, E. (1996). Rev. Med. Virol.6, 97–117. [PubMed]
  • Enraf–Nonius (1988). CAD-4 Manual. Version 5.0. Enraf–Nonius, Delft, The Netherlands.
  • Johnson, C. K. (1976). ORTEPII Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA.
  • Karapetyan, H., Tamazyan, R., Martirosyan, A., Hovhannesyan, V. & Gasparyan, S. (2002). Acta Cryst. C58, o399–o401. [PubMed]
  • Martirosyan, A. O., Gasparyan, S. P., Oganesyan, V. E., Mndzhoyan, Sh. L., Alexanyan, M. L., Nikishchenko, M. N. & Babayan, G. Sh. (2000). Chem. Heterocycl. Compd.36, 416–419.
  • Martirosyan, A. O., Hovhannesyan, V. E., Gasparyan, S. P., Karapetyan, H. A., Panosyan, G. A. & Martirosyan, V. O. (2004). Chem. Heterocycl. Compd.40, 1007–1008.
  • Sheldrick, G. M. (1997). SHELXS97 and SHELXL97 University of Göttingen, Germany.
  • Spek, A. L. (1997). HELENA University of Utrecht, The Netherlands.
  • Tamazyan, R., Karapetyan, H., Martirosyan, A., Hovhannesyan, V. & Gasparyan, S. (2002). Acta Cryst. C58, o386–o388. [PubMed]

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