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

The title compound, C(18)H(15)ClN(2)O(2), 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 = 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

Δρmax = 0.27 e Å−3

Δρmin = −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.

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

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

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

C18H15ClN2O2	Z = 2
Mr = 326.77	F(000) = 340
Triclinic, P1	Dx = 1.399 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.9749 (18) Å	Cell parameters from 22 reflections
b = 9.2184 (18) Å	θ = 12.6–16.6°
c = 9.912 (2) Å	µ = 0.26 mm−1
α = 86.90 (3)°	T = 293 K
β = 71.35 (3)°	Prism, colourless
γ = 88.27 (3)°	0.35 × 0.32 × 0.28 mm
V = 775.8 (3) Å3

Enraf–Nonius CAD-4 diffractometer	Rint = 0.035
Radiation source: fine-focus sealed tube	θmax = 30.0°, θmin = 2.2°
graphite	h = −12→12
θ/2θ scans	k = −12→12
7347 measured reflections	l = −13→13
4514 independent reflections	3 standard reflections every 180 min
3148 reflections with I > 2σ(I)	intensity decay: none

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)] = 0.046	Hydrogen site location: difference Fourier map
wR(F2) = 0.121	All H-atom parameters refined
S = 1.02	w = 1/[σ2(Fo2) + (0.0496P)2 + 0.2193P] where P = (Fo2 + 2Fc2)/3
4514 reflections	(Δ/σ)max < 0.001
268 parameters	Δρmax = 0.27 e Å−3
0 restraints	Δρmin = −0.31 e Å−3

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.

	x	y	z	Uiso*/Ueq
C2	0.70626 (17)	0.27403 (17)	1.00932 (16)	0.0333 (3)
C3	0.66409 (19)	0.11255 (18)	1.04089 (17)	0.0389 (3)
C5	0.91077 (18)	0.04305 (16)	0.85230 (16)	0.0343 (3)
C6	0.9468 (2)	−0.05252 (19)	0.74145 (19)	0.0432 (4)
C7	1.0802 (2)	−0.0350 (2)	0.6255 (2)	0.0488 (4)
C8	1.1788 (2)	0.0798 (2)	0.61835 (19)	0.0470 (4)
C9	1.1492 (2)	0.1717 (2)	0.72885 (19)	0.0418 (4)
C10	1.01455 (17)	0.15430 (16)	0.84775 (16)	0.0332 (3)
C11	0.99809 (17)	0.25083 (15)	0.96767 (16)	0.0319 (3)
C14	0.8259 (2)	0.37447 (19)	1.17444 (18)	0.0391 (3)
C15	0.6494 (2)	0.3646 (2)	1.24567 (19)	0.0493 (4)
C16	0.5879 (2)	0.3677 (2)	1.11921 (19)	0.0448 (4)
C17	0.71935 (17)	0.32632 (16)	0.85722 (16)	0.0335 (3)
C18	0.8016 (2)	0.45256 (19)	0.79868 (18)	0.0405 (4)
C19	0.8104 (2)	0.5045 (2)	0.6632 (2)	0.0519 (4)
C20	0.7365 (3)	0.4332 (2)	0.5842 (2)	0.0571 (5)
C21	0.6523 (3)	0.3101 (2)	0.6421 (2)	0.0562 (5)
C22	0.6436 (2)	0.2556 (2)	0.7781 (2)	0.0439 (4)
Cl	1.33908 (7)	0.10803 (8)	0.46554 (6)	0.0735 (2)
H4	0.745 (2)	−0.072 (2)	0.987 (2)	0.052 (6)*
H6	0.874 (2)	−0.135 (2)	0.747 (2)	0.047 (5)*
H7	1.101 (3)	−0.097 (2)	0.551 (2)	0.062 (6)*
H9	1.219 (2)	0.246 (2)	0.725 (2)	0.049 (5)*
H18	0.851 (2)	0.504 (2)	0.853 (2)	0.048 (5)*
H19	0.864 (3)	0.590 (3)	0.625 (2)	0.065 (7)*
H20	0.745 (3)	0.481 (2)	0.482 (3)	0.064 (6)*
H21	0.599 (3)	0.259 (2)	0.595 (2)	0.058 (6)*
H22	0.584 (2)	0.174 (2)	0.816 (2)	0.051 (6)*
H14A	0.856 (2)	0.473 (2)	1.1500 (19)	0.040 (5)*
H15A	0.608 (3)	0.445 (3)	1.311 (2)	0.065 (6)*
H16A	0.596 (2)	0.467 (2)	1.080 (2)	0.052 (6)*
H14B	0.886 (2)	0.328 (2)	1.233 (2)	0.048 (5)*
H15B	0.623 (2)	0.270 (2)	1.301 (2)	0.054 (6)*
H16B	0.484 (3)	0.331 (2)	1.139 (2)	0.055 (6)*
N1	0.85316 (15)	0.29356 (14)	1.04452 (13)	0.0327 (3)
N4	0.77286 (16)	0.01605 (16)	0.96731 (15)	0.0390 (3)
O12	1.11592 (13)	0.28878 (12)	0.99545 (13)	0.0410 (3)
O13	0.54222 (16)	0.07208 (16)	1.12946 (15)	0.0604 (4)

	U11	U22	U33	U12	U13	U23
C2	0.0302 (7)	0.0378 (8)	0.0323 (7)	−0.0007 (6)	−0.0102 (5)	−0.0035 (6)
C3	0.0373 (8)	0.0440 (9)	0.0352 (8)	−0.0102 (6)	−0.0106 (6)	−0.0001 (6)
C5	0.0389 (8)	0.0298 (7)	0.0351 (7)	0.0016 (6)	−0.0134 (6)	0.0008 (6)
C6	0.0543 (10)	0.0354 (8)	0.0433 (9)	0.0004 (7)	−0.0199 (8)	−0.0040 (7)
C7	0.0610 (11)	0.0468 (10)	0.0399 (9)	0.0125 (8)	−0.0178 (8)	−0.0093 (8)
C8	0.0423 (9)	0.0553 (11)	0.0373 (8)	0.0095 (8)	−0.0055 (7)	0.0000 (8)
C9	0.0352 (8)	0.0438 (9)	0.0437 (9)	0.0006 (7)	−0.0092 (7)	0.0006 (7)
C10	0.0324 (7)	0.0316 (7)	0.0359 (7)	0.0017 (5)	−0.0118 (6)	−0.0001 (6)
C11	0.0342 (7)	0.0263 (7)	0.0361 (7)	−0.0030 (5)	−0.0131 (6)	0.0040 (5)
C14	0.0480 (9)	0.0360 (8)	0.0367 (8)	0.0009 (7)	−0.0174 (7)	−0.0070 (7)
C15	0.0494 (10)	0.0602 (12)	0.0365 (9)	0.0050 (9)	−0.0102 (7)	−0.0112 (8)
C16	0.0394 (9)	0.0540 (11)	0.0407 (9)	0.0087 (8)	−0.0115 (7)	−0.0118 (8)
C17	0.0310 (7)	0.0363 (8)	0.0343 (7)	0.0047 (6)	−0.0119 (6)	−0.0050 (6)
C18	0.0417 (9)	0.0405 (9)	0.0418 (9)	−0.0001 (7)	−0.0168 (7)	−0.0032 (7)
C19	0.0563 (11)	0.0507 (11)	0.0463 (10)	−0.0007 (9)	−0.0147 (8)	0.0080 (8)
C20	0.0711 (13)	0.0641 (13)	0.0382 (9)	0.0087 (10)	−0.0213 (9)	−0.0014 (9)
C21	0.0687 (13)	0.0618 (12)	0.0508 (11)	0.0060 (10)	−0.0354 (10)	−0.0148 (9)
C22	0.0462 (9)	0.0440 (9)	0.0467 (9)	−0.0005 (7)	−0.0215 (8)	−0.0068 (8)
Cl	0.0554 (3)	0.0986 (5)	0.0498 (3)	0.0051 (3)	0.0065 (2)	−0.0053 (3)
N1	0.0349 (6)	0.0337 (6)	0.0318 (6)	−0.0002 (5)	−0.0134 (5)	−0.0037 (5)
N4	0.0418 (7)	0.0314 (7)	0.0417 (7)	−0.0078 (5)	−0.0106 (6)	0.0026 (6)
O12	0.0371 (6)	0.0362 (6)	0.0532 (7)	−0.0047 (4)	−0.0189 (5)	−0.0019 (5)
O13	0.0519 (8)	0.0631 (9)	0.0522 (8)	−0.0217 (7)	0.0050 (6)	−0.0049 (6)

C2—N1	1.4858 (19)	C14—C15	1.517 (3)
C2—C17	1.527 (2)	C14—H14A	0.956 (19)
C2—C3	1.538 (2)	C14—H14B	0.99 (2)
C2—C16	1.539 (2)	C15—C16	1.522 (3)
C3—O13	1.217 (2)	C15—H15A	0.99 (2)
C3—N4	1.356 (2)	C15—H15B	1.00 (2)
C5—C10	1.395 (2)	C16—H16A	0.97 (2)
C5—C6	1.396 (2)	C16—H16B	0.96 (2)
C5—N4	1.407 (2)	C17—C22	1.387 (2)
C6—C7	1.375 (3)	C17—C18	1.393 (2)
C6—H6	1.010 (19)	C18—C19	1.380 (3)
C7—C8	1.385 (3)	C18—H18	0.95 (2)
C7—H7	0.93 (2)	C19—C20	1.378 (3)
C8—C9	1.374 (3)	C19—H19	0.94 (2)
C8—Cl	1.7370 (19)	C20—C21	1.376 (3)
C9—C10	1.398 (2)	C20—H20	1.06 (2)
C9—H9	0.93 (2)	C21—C22	1.392 (3)
C10—C11	1.490 (2)	C21—H21	0.92 (2)
C11—O12	1.2391 (18)	C22—H22	0.92 (2)
C11—N1	1.340 (2)	N4—H4	0.85 (2)
C14—N1	1.472 (2)
N1—C2—C17	113.17 (12)	C14—C15—C16	102.64 (15)
N1—C2—C3	106.65 (12)	C14—C15—H15A	111.5 (13)
C17—C2—C3	113.09 (13)	C16—C15—H15A	113.8 (13)
N1—C2—C16	101.84 (12)	C14—C15—H15B	110.0 (12)
C17—C2—C16	111.26 (13)	C16—C15—H15B	109.7 (12)
C3—C2—C16	110.18 (14)	H15A—C15—H15B	109.1 (18)
O13—C3—N4	121.24 (16)	C15—C16—C2	104.63 (14)
O13—C3—C2	122.47 (16)	C15—C16—H16A	107.3 (12)
N4—C3—C2	116.26 (13)	C2—C16—H16A	107.6 (12)
C10—C5—C6	119.46 (15)	C15—C16—H16B	115.7 (13)
C10—C5—N4	123.50 (14)	C2—C16—H16B	109.7 (13)
C6—C5—N4	116.96 (15)	H16A—C16—H16B	111.4 (18)
C7—C6—C5	120.84 (17)	C22—C17—C18	118.84 (15)
C7—C6—H6	119.9 (11)	C22—C17—C2	121.50 (15)
C5—C6—H6	119.3 (11)	C18—C17—C2	119.56 (14)
C6—C7—C8	119.40 (17)	C19—C18—C17	120.52 (17)
C6—C7—H7	120.2 (14)	C19—C18—H18	119.7 (12)
C8—C7—H7	120.4 (14)	C17—C18—H18	119.8 (12)
C9—C8—C7	120.77 (17)	C20—C19—C18	120.54 (19)
C9—C8—Cl	120.40 (15)	C20—C19—H19	119.1 (14)
C7—C8—Cl	118.82 (15)	C18—C19—H19	120.3 (14)
C8—C9—C10	120.23 (17)	C21—C20—C19	119.41 (18)
C8—C9—H9	120.2 (12)	C21—C20—H20	124.0 (12)
C10—C9—H9	119.6 (12)	C19—C20—H20	116.5 (12)
C5—C10—C9	119.18 (15)	C20—C21—C22	120.71 (19)
C5—C10—C11	123.97 (14)	C20—C21—H21	123.0 (13)
C9—C10—C11	116.69 (14)	C22—C21—H21	116.3 (14)
O12—C11—N1	121.43 (14)	C17—C22—C21	119.96 (18)
O12—C11—C10	120.38 (14)	C17—C22—H22	120.9 (13)
N1—C11—C10	118.18 (13)	C21—C22—H22	119.1 (13)
N1—C14—C15	103.15 (14)	C11—N1—C14	121.27 (13)
N1—C14—H14A	110.2 (11)	C11—N1—C2	126.30 (12)
C15—C14—H14A	110.6 (11)	C14—N1—C2	112.36 (12)
N1—C14—H14B	109.6 (11)	C3—N4—C5	128.71 (14)
C15—C14—H14B	112.6 (11)	C3—N4—H4	113.7 (14)
H14A—C14—H14B	110.4 (15)	C5—N4—H4	116.9 (14)
N1—C2—C3—O13	118.43 (17)	C3—C2—C17—C22	23.3 (2)
C17—C2—C3—O13	−116.54 (18)	C16—C2—C17—C22	−101.29 (18)
C16—C2—C3—O13	8.7 (2)	N1—C2—C17—C18	−38.96 (19)
N1—C2—C3—N4	−59.63 (17)	C3—C2—C17—C18	−160.38 (14)
C17—C2—C3—N4	65.40 (18)	C16—C2—C17—C18	75.00 (18)
C16—C2—C3—N4	−169.39 (14)	C22—C17—C18—C19	−1.4 (2)
C10—C5—C6—C7	−2.5 (2)	C2—C17—C18—C19	−177.78 (16)
N4—C5—C6—C7	−179.40 (15)	C17—C18—C19—C20	0.7 (3)
C5—C6—C7—C8	−0.6 (3)	C18—C19—C20—C21	0.6 (3)
C6—C7—C8—C9	3.3 (3)	C19—C20—C21—C22	−1.2 (3)
C6—C7—C8—Cl	−175.46 (14)	C18—C17—C22—C21	0.8 (3)
C7—C8—C9—C10	−2.9 (3)	C2—C17—C22—C21	177.10 (16)
Cl—C8—C9—C10	175.88 (13)	C20—C21—C22—C17	0.5 (3)
C6—C5—C10—C9	2.9 (2)	O12—C11—N1—C14	−6.6 (2)
N4—C5—C10—C9	179.60 (14)	C10—C11—N1—C14	172.75 (13)
C6—C5—C10—C11	−172.22 (14)	O12—C11—N1—C2	170.27 (13)
N4—C5—C10—C11	4.5 (2)	C10—C11—N1—C2	−10.4 (2)
C8—C9—C10—C5	−0.3 (2)	C15—C14—N1—C11	−165.56 (14)
C8—C9—C10—C11	175.20 (15)	C15—C14—N1—C2	17.18 (18)
C5—C10—C11—O12	141.38 (15)	C17—C2—N1—C11	−50.6 (2)
C9—C10—C11—O12	−33.9 (2)	C3—C2—N1—C11	74.38 (18)
C5—C10—C11—N1	−38.0 (2)	C16—C2—N1—C11	−170.11 (15)
C9—C10—C11—N1	146.80 (14)	C17—C2—N1—C14	126.50 (14)
N1—C14—C15—C16	−34.22 (19)	C3—C2—N1—C14	−108.52 (14)
C14—C15—C16—C2	39.5 (2)	C16—C2—N1—C14	6.98 (17)
N1—C2—C16—C15	−28.50 (18)	O13—C3—N4—C5	172.76 (16)
C17—C2—C16—C15	−149.37 (15)	C2—C3—N4—C5	−9.1 (2)
C3—C2—C16—C15	84.38 (18)	C10—C5—N4—C3	43.9 (2)
N1—C2—C17—C22	144.75 (15)	C6—C5—N4—C3	−139.36 (17)

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)

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)

Symmetry code: (i) .