In the title compound, C
20H
17N
3O, 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.
Supporting information
CCDC reference: 677527
Key indicators
- Single-crystal X-ray study
- T = 293 K
- Mean
(C-C) = 0.002 Å
- R factor = 0.047
- wR factor = 0.130
- Data-to-parameter ratio = 16.6
checkCIF/PLATON results
No syntax errors found
Alert level C
PLAT154_ALERT_1_C The su's on the Cell Angles are Equal (x 10000) 3000 Deg.
PLAT230_ALERT_2_C Hirshfeld Test Diff for C2 - C7 .. 6.19 su
Alert level G
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature 293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature . 293 K
PLAT793_ALERT_2_G Check the Absolute Configuration of C2 ..... S
0 ALERT level A = In general: serious problem
0 ALERT level B = Potentially serious problem
2 ALERT level C = Check and explain
3 ALERT level G = General alerts; check
3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
2 ALERT type 2 Indicator that the structure model may be wrong or deficient
0 ALERT type 3 Indicator that the structure quality may be low
0 ALERT type 4 Improvement, methodology, query or suggestion
0 ALERT type 5 Informative message, check
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.
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.
Data collection: CAD-4 Manual (Enraf–Nonius, 1988); cell refinement: CAD-4 Manual (Enraf–Nonius, 1988); 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 (Bruker, 2000).
1-Benzyl-2-(1
H-indol-3-yl)-5-oxopyrrolidine-2-carbonitrile
top
Crystal data top
C20H17N3O | Z = 2 |
Mr = 315.37 | F(000) = 332 |
Triclinic, P1 | Dx = 1.286 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.5781 (15) Å | Cell parameters from 22 reflections |
b = 9.4521 (19) Å | θ = 14.2–17.5° |
c = 12.409 (3) Å | µ = 0.08 mm−1 |
α = 78.02 (3)° | T = 293 K |
β = 83.05 (3)° | Prism, colourless |
γ = 69.68 (3)° | 0.4 × 0.3 × 0.2 mm |
V = 814.2 (3) Å3 | |
Data collection top
Enraf–Nonius CAD-4 diffractometer | Rint = 0.020 |
Radiation source: fine-focus sealed tube | θmax = 30.0°, θmin = 1.7° |
Graphite monochromator | h = −10→10 |
θ/2θ scans | k = −13→13 |
9470 measured reflections | l = −17→17 |
4735 independent reflections | 3 standard reflections every 180 min |
3450 reflections with I > 2σ(I) | intensity decay: none |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.047 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.130 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0649P)2 + 0.0907P] where P = (Fo2 + 2Fc2)/3 |
4735 reflections | (Δ/σ)max < 0.001 |
285 parameters | Δρmax = 0.18 e Å−3 |
0 restraints | Δρmin = −0.20 e Å−3 |
Crystal data top
C20H17N3O | γ = 69.68 (3)° |
Mr = 315.37 | V = 814.2 (3) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.5781 (15) Å | Mo Kα radiation |
b = 9.4521 (19) Å | µ = 0.08 mm−1 |
c = 12.409 (3) Å | T = 293 K |
α = 78.02 (3)° | 0.4 × 0.3 × 0.2 mm |
β = 83.05 (3)° | |
Data collection top
Enraf–Nonius CAD-4 diffractometer | Rint = 0.020 |
9470 measured reflections | 3 standard reflections every 180 min |
4735 independent reflections | intensity decay: none |
3450 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.047 | 0 restraints |
wR(F2) = 0.130 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.02 | Δρmax = 0.18 e Å−3 |
4735 reflections | Δρmin = −0.20 e Å−3 |
285 parameters | |
Special details top
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) top | x | y | z | Uiso*/Ueq | |
N1 | 0.22574 (14) | 0.71961 (10) | 0.23198 (8) | 0.0367 (2) | |
C2 | 0.20774 (17) | 0.64700 (12) | 0.14116 (9) | 0.0385 (2) | |
C3 | 0.3119 (3) | 0.72278 (16) | 0.04282 (12) | 0.0552 (4) | |
H3A | 0.448 (3) | 0.655 (2) | 0.0402 (14) | 0.066 (5)* | |
H3B | 0.258 (2) | 0.728 (2) | −0.0253 (16) | 0.069 (5)* | |
C4 | 0.2913 (3) | 0.87637 (17) | 0.07212 (14) | 0.0642 (4) | |
H4A | 0.182 (3) | 0.955 (3) | 0.0430 (19) | 0.096 (7)* | |
H4B | 0.408 (3) | 0.908 (3) | 0.049 (2) | 0.102 (7)* | |
C5 | 0.26566 (17) | 0.85107 (13) | 0.19576 (12) | 0.0453 (3) | |
O6 | 0.27772 (15) | 0.93414 (11) | 0.25649 (10) | 0.0628 (3) | |
C7 | 0.0051 (2) | 0.69595 (15) | 0.11645 (11) | 0.0503 (3) | |
N8 | −0.1486 (2) | 0.73626 (18) | 0.09409 (14) | 0.0761 (4) | |
C9 | 0.28897 (17) | 0.47561 (12) | 0.16540 (9) | 0.0379 (2) | |
C10 | 0.2034 (2) | 0.37431 (15) | 0.15315 (11) | 0.0480 (3) | |
H10 | 0.076 (2) | 0.3968 (19) | 0.1273 (14) | 0.063 (5)* | |
H11 | 0.298 (3) | 0.140 (2) | 0.1869 (15) | 0.073 (5)* | |
N11 | 0.32401 (19) | 0.22756 (13) | 0.18058 (10) | 0.0543 (3) | |
C12 | 0.48874 (19) | 0.23143 (13) | 0.21285 (10) | 0.0435 (3) | |
C13 | 0.6498 (2) | 0.11135 (15) | 0.24876 (12) | 0.0574 (4) | |
H13 | 0.655 (2) | 0.009 (2) | 0.2546 (15) | 0.068 (5)* | |
C14 | 0.7955 (2) | 0.14884 (19) | 0.27645 (14) | 0.0656 (4) | |
H14 | 0.911 (3) | 0.066 (2) | 0.3034 (16) | 0.079 (5)* | |
C15 | 0.7826 (2) | 0.30164 (19) | 0.26931 (15) | 0.0641 (4) | |
H15 | 0.887 (3) | 0.324 (2) | 0.2894 (16) | 0.078 (5)* | |
C16 | 0.62465 (19) | 0.42094 (15) | 0.23300 (12) | 0.0498 (3) | |
H16 | 0.620 (2) | 0.5269 (19) | 0.2264 (14) | 0.059 (4)* | |
C17 | 0.47300 (17) | 0.38670 (12) | 0.20376 (9) | 0.0379 (2) | |
C18 | 0.20486 (17) | 0.65739 (14) | 0.34923 (10) | 0.0395 (2) | |
H18A | 0.258 (2) | 0.5459 (17) | 0.3571 (12) | 0.047 (4)* | |
H18B | 0.280 (2) | 0.6986 (17) | 0.3851 (13) | 0.054 (4)* | |
C19 | 0.00691 (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) | |
H24 | 0.038 (2) | 0.858 (2) | 0.4834 (14) | 0.065 (5)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0439 (5) | 0.0279 (4) | 0.0399 (5) | −0.0152 (4) | 0.0056 (4) | −0.0083 (3) |
C2 | 0.0494 (6) | 0.0315 (5) | 0.0350 (5) | −0.0157 (5) | 0.0037 (5) | −0.0062 (4) |
C3 | 0.0742 (10) | 0.0429 (7) | 0.0425 (7) | −0.0210 (7) | 0.0150 (7) | −0.0026 (5) |
C4 | 0.0842 (11) | 0.0384 (7) | 0.0649 (9) | −0.0266 (7) | 0.0159 (8) | 0.0017 (6) |
C5 | 0.0426 (6) | 0.0272 (5) | 0.0655 (8) | −0.0132 (4) | 0.0051 (5) | −0.0089 (5) |
O6 | 0.0691 (7) | 0.0387 (5) | 0.0905 (8) | −0.0253 (5) | 0.0011 (6) | −0.0228 (5) |
C7 | 0.0609 (8) | 0.0433 (6) | 0.0447 (7) | −0.0147 (6) | −0.0096 (6) | −0.0040 (5) |
N8 | 0.0693 (9) | 0.0762 (10) | 0.0782 (10) | −0.0154 (7) | −0.0267 (8) | −0.0059 (8) |
C9 | 0.0500 (6) | 0.0304 (5) | 0.0358 (5) | −0.0170 (5) | 0.0045 (5) | −0.0089 (4) |
C10 | 0.0624 (8) | 0.0415 (6) | 0.0490 (7) | −0.0263 (6) | −0.0024 (6) | −0.0121 (5) |
N11 | 0.0788 (8) | 0.0341 (5) | 0.0594 (7) | −0.0295 (5) | 0.0002 (6) | −0.0122 (5) |
C12 | 0.0605 (7) | 0.0309 (5) | 0.0390 (6) | −0.0180 (5) | 0.0111 (5) | −0.0089 (4) |
C13 | 0.0738 (10) | 0.0326 (6) | 0.0532 (8) | −0.0100 (6) | 0.0146 (7) | −0.0041 (5) |
C14 | 0.0545 (9) | 0.0536 (8) | 0.0666 (10) | −0.0005 (7) | 0.0081 (7) | 0.0005 (7) |
C15 | 0.0467 (8) | 0.0635 (9) | 0.0771 (11) | −0.0168 (7) | 0.0016 (7) | −0.0070 (8) |
C16 | 0.0471 (7) | 0.0418 (6) | 0.0622 (8) | −0.0188 (5) | 0.0056 (6) | −0.0105 (6) |
C17 | 0.0475 (6) | 0.0299 (5) | 0.0369 (5) | −0.0156 (4) | 0.0097 (5) | −0.0095 (4) |
C18 | 0.0411 (6) | 0.0387 (6) | 0.0377 (6) | −0.0114 (5) | −0.0004 (5) | −0.0090 (4) |
C19 | 0.0429 (6) | 0.0351 (5) | 0.0307 (5) | −0.0093 (4) | 0.0006 (4) | −0.0049 (4) |
C20 | 0.0553 (8) | 0.0719 (9) | 0.0436 (7) | −0.0304 (7) | 0.0050 (6) | −0.0144 (6) |
C21 | 0.0521 (9) | 0.1182 (16) | 0.0534 (9) | −0.0380 (10) | 0.0035 (7) | −0.0031 (9) |
C22 | 0.0529 (9) | 0.0940 (13) | 0.0560 (9) | −0.0023 (9) | 0.0154 (7) | 0.0060 (9) |
C23 | 0.0899 (13) | 0.0588 (9) | 0.0509 (8) | 0.0010 (9) | 0.0230 (8) | −0.0149 (7) |
C24 | 0.0726 (9) | 0.0435 (7) | 0.0429 (7) | −0.0147 (6) | 0.0073 (6) | −0.0138 (5) |
Geometric parameters (Å, º) top
N1—C5 | 1.3542 (15) | C13—C14 | 1.370 (3) |
N1—C18 | 1.4634 (16) | C13—H13 | 0.944 (18) |
N1—C2 | 1.4775 (15) | C14—C15 | 1.398 (2) |
C2—C7 | 1.493 (2) | C14—H14 | 0.99 (2) |
C2—C9 | 1.4979 (16) | C15—C16 | 1.375 (2) |
C2—C3 | 1.5562 (18) | C15—H15 | 0.96 (2) |
C3—C4 | 1.521 (2) | C16—C17 | 1.4018 (18) |
C3—H3A | 1.009 (18) | C16—H16 | 0.976 (16) |
C3—H3B | 0.969 (18) | C18—C19 | 1.5076 (17) |
C4—C5 | 1.502 (2) | C18—H18A | 0.977 (15) |
C4—H4A | 0.95 (2) | C18—H18B | 0.983 (16) |
C4—H4B | 1.02 (2) | C19—C20 | 1.3824 (19) |
C5—O6 | 1.2269 (16) | C19—C24 | 1.3842 (17) |
C7—N8 | 1.142 (2) | C20—C21 | 1.383 (2) |
C9—C10 | 1.3695 (17) | C20—H20 | 0.989 (18) |
C9—C17 | 1.4348 (18) | C21—C22 | 1.366 (3) |
C10—N11 | 1.3689 (19) | C21—H21 | 0.95 (2) |
C10—H10 | 0.994 (17) | C22—C23 | 1.365 (3) |
N11—C12 | 1.3707 (19) | C22—H22 | 1.00 (2) |
N11—H11 | 0.90 (2) | C23—C24 | 1.399 (2) |
C12—C13 | 1.391 (2) | C23—H23 | 0.94 (2) |
C12—C17 | 1.4120 (15) | C24—H24 | 0.986 (17) |
| | | |
C5—N1—C18 | 122.70 (10) | C14—C13—H13 | 122.7 (10) |
C5—N1—C2 | 112.91 (10) | C12—C13—H13 | 120.0 (10) |
C18—N1—C2 | 124.39 (9) | C13—C14—C15 | 121.35 (15) |
N1—C2—C7 | 109.37 (10) | C13—C14—H14 | 119.6 (11) |
N1—C2—C9 | 113.04 (10) | C15—C14—H14 | 119.1 (11) |
C7—C2—C9 | 110.17 (11) | C16—C15—C14 | 121.65 (16) |
N1—C2—C3 | 101.87 (10) | C16—C15—H15 | 118.9 (11) |
C7—C2—C3 | 108.24 (12) | C14—C15—H15 | 119.4 (11) |
C9—C2—C3 | 113.77 (10) | C15—C16—C17 | 118.50 (13) |
C4—C3—C2 | 104.09 (11) | C15—C16—H16 | 120.4 (9) |
C4—C3—H3A | 111.4 (10) | C17—C16—H16 | 121.1 (9) |
C2—C3—H3A | 107.7 (10) | C16—C17—C12 | 118.72 (12) |
C4—C3—H3B | 115.6 (11) | C16—C17—C9 | 134.95 (11) |
C2—C3—H3B | 109.1 (11) | C12—C17—C9 | 106.31 (11) |
H3A—C3—H3B | 108.5 (14) | N1—C18—C19 | 116.05 (10) |
C5—C4—C3 | 104.26 (11) | N1—C18—H18A | 106.8 (9) |
C5—C4—H4A | 108.1 (14) | C19—C18—H18A | 109.9 (8) |
C3—C4—H4A | 112.0 (13) | N1—C18—H18B | 103.9 (9) |
C5—C4—H4B | 109.1 (14) | C19—C18—H18B | 108.7 (9) |
C3—C4—H4B | 112.6 (13) | H18A—C18—H18B | 111.5 (12) |
H4A—C4—H4B | 110.6 (19) | C20—C19—C24 | 118.62 (13) |
O6—C5—N1 | 124.06 (13) | C20—C19—C18 | 120.58 (11) |
O6—C5—C4 | 126.73 (12) | C24—C19—C18 | 120.70 (12) |
N1—C5—C4 | 109.21 (11) | C19—C20—C21 | 120.72 (15) |
N8—C7—C2 | 177.60 (16) | C19—C20—H20 | 118.9 (10) |
C10—C9—C17 | 107.09 (11) | C21—C20—H20 | 120.3 (10) |
C10—C9—C2 | 126.59 (12) | C22—C21—C20 | 120.49 (18) |
C17—C9—C2 | 126.31 (10) | C22—C21—H21 | 118.2 (14) |
N11—C10—C9 | 109.47 (13) | C20—C21—H21 | 121.3 (14) |
N11—C10—H10 | 122.1 (10) | C23—C22—C21 | 119.72 (16) |
C9—C10—H10 | 128.4 (10) | C23—C22—H22 | 120.8 (12) |
C10—N11—C12 | 109.29 (11) | C21—C22—H22 | 119.5 (12) |
C10—N11—H11 | 127.3 (11) | C22—C23—C24 | 120.51 (16) |
C12—N11—H11 | 122.9 (11) | C22—C23—H23 | 122.7 (14) |
N11—C12—C13 | 129.75 (12) | C24—C23—H23 | 116.8 (14) |
N11—C12—C17 | 107.83 (12) | C19—C24—C23 | 119.93 (17) |
C13—C12—C17 | 122.42 (14) | C19—C24—H24 | 118.7 (10) |
C14—C13—C12 | 117.34 (13) | C23—C24—H24 | 121.3 (10) |
Hydrogen-bond geometry (Å, º) top
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) |
Symmetry code: (i) x, y−1, z. |
Experimental details
Crystal data |
Chemical formula | C20H17N3O |
Mr | 315.37 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 7.5781 (15), 9.4521 (19), 12.409 (3) |
α, β, γ (°) | 78.02 (3), 83.05 (3), 69.68 (3) |
V (Å3) | 814.2 (3) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.4 × 0.3 × 0.2 |
|
Data collection |
Diffractometer | Enraf–Nonius CAD-4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9470, 4735, 3450 |
Rint | 0.020 |
(sin θ/λ)max (Å−1) | 0.703 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.047, 0.130, 1.02 |
No. of reflections | 4735 |
No. of parameters | 285 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.18, −0.20 |
Hydrogen-bond geometry (Å, º) top
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) |
Symmetry code: (i) x, y−1, z. |
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).