(S)-Ethyl 1,2,3,9-tetra­hydro­pyrrolo[2,1-b]quinazoline-1-carboxyl­ate

Ma, C.; Du, G.-J.; Tian, Y.; Sha, Y.; Cheng, M.-S.

doi:10.1107/S1600536808008908

organic compounds

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Volume 64| Part 5| May 2008| Page o815

doi:10.1107/S1600536808008908

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(S)-Ethyl 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylate

Chao Ma,^a ^* Gui-Jie Du,^b Yu Tian,^a Yu Sha ^a and Mao-Sheng Cheng ^a

^aSchool of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Mail Box 40, 103 Wenhua Road, Shenhe District, Shenyang 110016, People's Republic of China, and ^bJinZhou JiuTai Pharmaceutical Co.,Ltd, Taianli, Taihe District, Jinzhou 121012, People's Republic of China
^*Correspondence e-mail: mscheng@syphu.edu.cn

(Received 19 March 2008; accepted 2 April 2008; online 10 April 2008)

The title chiral compound, C₁₄H₁₆N₂O₂, was prepared by esterification of (S)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-carboxylic acid in the presence of HCl/EtOH. In the molecule, the quinazoline ring is non-planar and exhibits a distorted half-chair conformation, while the five-membered ring shows a typical envelope conformation. Intermolecular C—H⋯N hydrogen bonding helps to stabilize the crystal structure.

Related literature

For general background, see: Cheng et al. (2006 ); Hua et al. (2002 ).

Experimental

Crystal data

C₁₄H₁₆N₂O₂
M_r = 244.29
Monoclinic, P 2₁
a = 6.0545 (8) Å
b = 9.1438 (13) Å
c = 11.5228 (16) Å
β = 92.905 (2)°
V = 637.10 (15) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 187 (2) K
0.29 × 0.22 × 0.19 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: none
3430 measured reflections
1246 independent reflections
1166 reflections with I > 2σ(I)
R_int = 0.016

Refinement

R[F² > 2σ(F²)] = 0.031
wR(F²) = 0.076
S = 1.08
1246 reflections
164 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.11 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5⋯N2ⁱ	0.95	2.59	3.523 (3)	169
Symmetry code: (i) $[-x+3, y+{\script{1\over 2}}, -z]$ .

Data collection: SMART (Bruker, 1997 ); cell refinement: SAINT (Bruker, 1999 ); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL-Plus (Sheldrick, 2008); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808008908/xu2409sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808008908/xu2409Isup2.hkl

checkCIF report

Comment top

The title chiral compound is a derivate of (S)-1,2,3,9-tetrahydro-pyrrolo(2,1 - b)quinazolin-1-carboxylic acid (Linaria acid). Linaria acid is a nature compound, was isolated from the Linaria vulgaris (Hua et al., 2002). Linaria vulgaris is a grassy plant that occurs in northeast China. The plant is used in traditional folk medicine for the treatment of coughs and asthma and as an expectorant. As part of our search on new Linaria acid derivate compounds (Cheng et al., 2006), the title compound is recently synthesized and its crystal structure is reported here.

The molecular structure is shown in Fig. 1. The bond lengths and angles are within normal ranges. The quinazoline moiety is not planar, the central N-heterocyclic ring shows a distorted conformation, with atom N1 and C8 displaced by 0.420 Å and 0.257 Å from the mean plane defined by atoms C1/C2/C7/N2. The five-membered ring adopts an envelope conformation, with atom C10 deviating by 0.443 Å from the plane formed by the other atoms in the ring. Atom C11 of the title molecule is chiral, S configuration was assigned to this atom based on the known chirality of the equivalent atom in the starting material. An intermolecular C—H···N hydrogen bonding (Table 1) helps to stabilize the crystal structure.

Related literature top

For general background, see: Cheng et al. (2006); Hua et al. (2002).

Experimental top

A rapid stream of hydrogen chloride was passed for 3 h into absolute ethanol (200 ml) in an icebath. To this solution was added (S)-1,2,3,9-tetrahydro-pyrrolo(2,1 - b)quinazolin-1-carboxylic acid (4.32 g, 20 mmol), and this solution was refluxed for 3 h. The ethanol was removed under vacuum. The pure product was obtained through silica gel chromatography (eluant: petroleum ether/ethyl acetate, 1:10). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a dilute solution of the title compound in ethyl acetate at room temperature.

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL-Plus (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. The structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme.
	Fig. 2. The molecular packing of the title compound.

(S)-Ethyl 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylate top

Crystal data top

C₁₄H₁₆N₂O₂	F(000) = 260
M_r = 244.29	D_x = 1.273 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 1588 reflections
a = 6.0545 (8) Å	θ = 2.9–25.0°
b = 9.1438 (13) Å	µ = 0.09 mm⁻¹
c = 11.5228 (16) Å	T = 187 K
β = 92.905 (2)°	Block, colorless
V = 637.10 (15) Å³	0.29 × 0.22 × 0.19 mm
Z = 2

Data collection top

Bruker SMART APEX CCD area-detector diffractometer	1166 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.016
Graphite monochromator	θ_max = 25.4°, θ_min = 1.8°
ϕ and ω scans	h = −7→7
3430 measured reflections	k = −11→5
1246 independent reflections	l = −13→13

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)] = 0.031	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.076	H-atom parameters constrained
S = 1.08	w = 1/[σ²(F_o²) + (0.0381P)² + 0.082P] where P = (F_o² + 2F_c²)/3
1246 reflections	(Δ/σ)_max = 0.001
164 parameters	Δρ_max = 0.11 e Å⁻³
1 restraint	Δρ_min = −0.14 e Å⁻³

Crystal data top

C₁₄H₁₆N₂O₂	V = 637.10 (15) Å³
M_r = 244.29	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 6.0545 (8) Å	µ = 0.09 mm⁻¹
b = 9.1438 (13) Å	T = 187 K
c = 11.5228 (16) Å	0.29 × 0.22 × 0.19 mm
β = 92.905 (2)°

Data collection top

Bruker SMART APEX CCD area-detector diffractometer	1166 reflections with I > 2σ(I)
3430 measured reflections	R_int = 0.016
1246 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.031	1 restraint
wR(F²) = 0.076	H-atom parameters constrained
S = 1.08	Δρ_max = 0.11 e Å⁻³
1246 reflections	Δρ_min = −0.14 e Å⁻³
164 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	U_iso*/U_eq
C1	0.8935 (4)	0.4244 (2)	0.24523 (19)	0.0343 (5)
H1A	0.9134	0.4636	0.3252	0.041*
H1B	0.7364	0.4369	0.2188	0.041*
C2	1.0401 (3)	0.5062 (2)	0.16534 (17)	0.0301 (5)
C3	0.9824 (4)	0.6432 (3)	0.12309 (18)	0.0360 (5)
H3	0.8452	0.6850	0.1421	0.043*
C4	1.1216 (4)	0.7206 (3)	0.05344 (18)	0.0403 (5)
H4	1.0813	0.8155	0.0263	0.048*
C5	1.3199 (4)	0.6585 (3)	0.02377 (18)	0.0385 (5)
H5	1.4157	0.7105	−0.0244	0.046*
C6	1.3781 (4)	0.5209 (3)	0.06430 (18)	0.0348 (5)
H6	1.5135	0.4786	0.0430	0.042*
C7	1.2412 (3)	0.4433 (2)	0.13602 (16)	0.0295 (5)
C8	1.1581 (3)	0.2248 (3)	0.22061 (16)	0.0309 (5)
C9	1.1809 (4)	0.0669 (3)	0.2550 (2)	0.0413 (6)
H9A	1.2678	0.0565	0.3297	0.050*
H9B	1.2532	0.0098	0.1946	0.050*
C10	0.9409 (4)	0.0170 (3)	0.2667 (2)	0.0428 (6)
H10A	0.9307	−0.0560	0.3297	0.051*
H10B	0.8795	−0.0261	0.1931	0.051*
C11	0.8183 (3)	0.1590 (3)	0.29605 (17)	0.0351 (5)
H11	0.6653	0.1587	0.2590	0.042*
C12	0.8108 (4)	0.1795 (3)	0.42708 (19)	0.0387 (6)
C13	0.6211 (4)	0.1044 (4)	0.5926 (2)	0.0562 (8)
H13A	0.7692	0.1147	0.6322	0.067*
H13B	0.5573	0.0102	0.6169	0.067*
C14	0.4776 (5)	0.2258 (4)	0.6279 (2)	0.0595 (7)
H14A	0.3311	0.2158	0.5886	0.089*
H14B	0.5433	0.3193	0.6063	0.089*
H14C	0.4636	0.2228	0.7123	0.089*
N1	0.9521 (3)	0.2705 (2)	0.24410 (14)	0.0315 (4)
N2	1.3078 (3)	0.3013 (2)	0.17238 (15)	0.0328 (4)
O1	0.6431 (3)	0.1034 (2)	0.46705 (14)	0.0454 (4)
O2	0.9396 (3)	0.2508 (3)	0.48572 (14)	0.0652 (6)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0276 (11)	0.0351 (13)	0.0405 (11)	0.0037 (10)	0.0048 (9)	−0.0020 (10)
C2	0.0287 (10)	0.0315 (12)	0.0298 (10)	−0.0010 (9)	−0.0006 (8)	−0.0023 (9)
C3	0.0340 (11)	0.0361 (12)	0.0380 (11)	0.0045 (10)	0.0007 (9)	−0.0005 (10)
C4	0.0511 (14)	0.0309 (12)	0.0383 (11)	0.0021 (11)	−0.0026 (10)	0.0044 (11)
C5	0.0450 (12)	0.0389 (13)	0.0316 (11)	−0.0062 (11)	0.0036 (9)	0.0033 (10)
C6	0.0296 (10)	0.0399 (13)	0.0351 (11)	−0.0049 (10)	0.0042 (9)	−0.0039 (11)
C7	0.0276 (10)	0.0320 (12)	0.0285 (10)	0.0003 (9)	−0.0014 (8)	−0.0011 (9)
C8	0.0282 (10)	0.0337 (11)	0.0307 (10)	0.0034 (10)	0.0013 (8)	−0.0002 (9)
C9	0.0376 (12)	0.0370 (14)	0.0495 (14)	0.0034 (11)	0.0055 (10)	0.0055 (10)
C10	0.0451 (14)	0.0366 (13)	0.0471 (13)	−0.0041 (11)	0.0065 (11)	0.0043 (11)
C11	0.0279 (10)	0.0412 (13)	0.0361 (11)	−0.0061 (10)	0.0011 (8)	0.0062 (10)
C12	0.0308 (11)	0.0479 (15)	0.0372 (11)	0.0032 (10)	0.0001 (9)	0.0092 (10)
C13	0.0580 (16)	0.073 (2)	0.0391 (13)	0.0063 (16)	0.0170 (12)	0.0200 (14)
C14	0.0631 (16)	0.0670 (18)	0.0495 (14)	−0.0021 (16)	0.0120 (12)	−0.0016 (15)
N1	0.0274 (9)	0.0328 (11)	0.0347 (9)	0.0008 (8)	0.0050 (7)	0.0042 (8)
N2	0.0260 (9)	0.0347 (11)	0.0380 (9)	0.0017 (8)	0.0046 (7)	0.0019 (8)
O1	0.0442 (9)	0.0514 (11)	0.0418 (9)	−0.0038 (8)	0.0140 (7)	0.0093 (8)
O2	0.0519 (11)	0.1046 (18)	0.0385 (9)	−0.0257 (12)	−0.0036 (8)	0.0003 (11)

Geometric parameters (Å, º) top

C1—N1	1.452 (3)	C9—C10	1.536 (3)
C1—C2	1.509 (3)	C9—H9A	0.9900
C1—H1A	0.9900	C9—H9B	0.9900
C1—H1B	0.9900	C10—C11	1.541 (4)
C2—C3	1.383 (3)	C10—H10A	0.9900
C2—C7	1.403 (3)	C10—H10B	0.9900
C3—C4	1.387 (3)	C11—N1	1.450 (3)
C3—H3	0.9500	C11—C12	1.524 (3)
C4—C5	1.387 (3)	C11—H11	1.0000
C4—H4	0.9500	C12—O2	1.199 (3)
C5—C6	1.381 (3)	C12—O1	1.332 (3)
C5—H5	0.9500	C13—O1	1.459 (3)
C6—C7	1.394 (3)	C13—C14	1.480 (4)
C6—H6	0.9500	C13—H13A	0.9900
C7—N2	1.416 (3)	C13—H13B	0.9900
C8—N2	1.293 (3)	C14—H14A	0.9800
C8—N1	1.355 (3)	C14—H14B	0.9800
C8—C9	1.502 (3)	C14—H14C	0.9800

N1—C1—C2	108.86 (17)	C9—C10—C11	103.7 (2)
N1—C1—H1A	109.9	C9—C10—H10A	111.0
C2—C1—H1A	109.9	C11—C10—H10A	111.0
N1—C1—H1B	109.9	C9—C10—H10B	111.0
C2—C1—H1B	109.9	C11—C10—H10B	111.0
H1A—C1—H1B	108.3	H10A—C10—H10B	109.0
C3—C2—C7	119.57 (19)	N1—C11—C12	111.57 (19)
C3—C2—C1	121.18 (19)	N1—C11—C10	102.49 (17)
C7—C2—C1	119.23 (18)	C12—C11—C10	111.05 (18)
C2—C3—C4	121.1 (2)	N1—C11—H11	110.5
C2—C3—H3	119.5	C12—C11—H11	110.5
C4—C3—H3	119.5	C10—C11—H11	110.5
C5—C4—C3	119.5 (2)	O2—C12—O1	125.1 (2)
C5—C4—H4	120.2	O2—C12—C11	125.0 (2)
C3—C4—H4	120.2	O1—C12—C11	109.86 (19)
C6—C5—C4	119.9 (2)	O1—C13—C14	111.2 (2)
C6—C5—H5	120.0	O1—C13—H13A	109.4
C4—C5—H5	120.0	C14—C13—H13A	109.4
C5—C6—C7	121.0 (2)	O1—C13—H13B	109.4
C5—C6—H6	119.5	C14—C13—H13B	109.4
C7—C6—H6	119.5	H13A—C13—H13B	108.0
C6—C7—C2	118.89 (19)	C13—C14—H14A	109.5
C6—C7—N2	118.26 (19)	C13—C14—H14B	109.5
C2—C7—N2	122.80 (18)	H14A—C14—H14B	109.5
N2—C8—N1	126.3 (2)	C13—C14—H14C	109.5
N2—C8—C9	125.2 (2)	H14A—C14—H14C	109.5
N1—C8—C9	108.43 (19)	H14B—C14—H14C	109.5
C8—C9—C10	103.55 (19)	C8—N1—C11	113.89 (18)
C8—C9—H9A	111.0	C8—N1—C1	121.87 (18)
C10—C9—H9A	111.1	C11—N1—C1	122.40 (17)
C8—C9—H9B	111.1	C8—N2—C7	115.34 (18)
C10—C9—H9B	111.1	C12—O1—C13	116.7 (2)
H9A—C9—H9B	109.0

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···N2ⁱ	0.95	2.59	3.523 (3)	169

Symmetry code: (i) −x+3, y+1/2, −z.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₆N₂O₂
M_r	244.29
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	187
a, b, c (Å)	6.0545 (8), 9.1438 (13), 11.5228 (16)
β (°)	92.905 (2)
V (Å³)	637.10 (15)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.29 × 0.22 × 0.19

Data collection
Diffractometer	Bruker SMART APEX CCD area-detector diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	3430, 1246, 1166
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.031, 0.076, 1.08
No. of reflections	1246
No. of parameters	164
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.11, −0.14

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1999), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL-Plus (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5···N2ⁱ	0.95	2.59	3.523 (3)	169

Symmetry code: (i) −x+3, y+1/2, −z.

References

Bruker (1997). SMART. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (1999). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cheng, M.-S., Li, Q., Lin, B., Sha, Y., Ren, J.-H., He, Y., Wang, Q.-H., Hua, H.-M. & Kenneth, R. (2006). Tetrahedron Asymmetry, 17, 179–183. Web of Science CSD CrossRef CAS Google Scholar
Hua, H.-M., Cheng, M.-S., Li, X. & Pei, Y.-H. (2002). Chem. Pharm. Bull. 50, 1393–1394. Web of Science CSD CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 64| Part 5| May 2008| Page o815

doi:10.1107/S1600536808008908

Open

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