organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2056-9890

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

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[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.]); Hua et al. (2002[Hua, H.-M., Cheng, M.-S., Li, X. & Pei, Y.-H. (2002). Chem. Pharm. Bull. 50, 1393-1394.]).

[Scheme 1]

Experimental

Crystal data
  • C14H16N2O2

  • Mr = 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)

  • Rint = 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

  • Δρmax = 0.11 e Å−3

  • Δρmin = −0.14 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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[Bruker (1997). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 1999[Bruker (1999). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL-Plus (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL97.

Supporting information


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.

Refinement top

All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H = 0.95, 0.99, 0.98 and 1.00 Å for phenyl, methylene, methyl and tertiary H atoms, respectively, with Uiso(H) = xUeq(C), where x=1.5 for methyl H, and x=1.2 for all other H atoms. Based on known chirality of the equivalent atom in the starting material, the S chirality at C11 was assigned. Friedel pairs were merged.

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
[Figure 1] Fig. 1. The structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] 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
C14H16N2O2F(000) = 260
Mr = 244.29Dx = 1.273 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 1588 reflections
a = 6.0545 (8) Åθ = 2.9–25.0°
b = 9.1438 (13) ŵ = 0.09 mm1
c = 11.5228 (16) ÅT = 187 K
β = 92.905 (2)°Block, colorless
V = 637.10 (15) Å30.29 × 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 tubeRint = 0.016
Graphite monochromatorθmax = 25.4°, θmin = 1.8°
ϕ and ω scansh = 77
3430 measured reflectionsk = 115
1246 independent reflectionsl = 1313
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.031Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.076H-atom parameters constrained
S = 1.08 w = 1/[σ2(Fo2) + (0.0381P)2 + 0.082P]
where P = (Fo2 + 2Fc2)/3
1246 reflections(Δ/σ)max = 0.001
164 parametersΔρmax = 0.11 e Å3
1 restraintΔρmin = 0.14 e Å3
Crystal data top
C14H16N2O2V = 637.10 (15) Å3
Mr = 244.29Z = 2
Monoclinic, P21Mo Kα radiation
a = 6.0545 (8) ŵ = 0.09 mm1
b = 9.1438 (13) ÅT = 187 K
c = 11.5228 (16) Å0.29 × 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 reflectionsRint = 0.016
1246 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0311 restraint
wR(F2) = 0.076H-atom parameters constrained
S = 1.08Δρmax = 0.11 e Å3
1246 reflectionsΔρmin = 0.14 e Å3
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
xyzUiso*/Ueq
C10.8935 (4)0.4244 (2)0.24523 (19)0.0343 (5)
H1A0.91340.46360.32520.041*
H1B0.73640.43690.21880.041*
C21.0401 (3)0.5062 (2)0.16534 (17)0.0301 (5)
C30.9824 (4)0.6432 (3)0.12309 (18)0.0360 (5)
H30.84520.68500.14210.043*
C41.1216 (4)0.7206 (3)0.05344 (18)0.0403 (5)
H41.08130.81550.02630.048*
C51.3199 (4)0.6585 (3)0.02377 (18)0.0385 (5)
H51.41570.71050.02440.046*
C61.3781 (4)0.5209 (3)0.06430 (18)0.0348 (5)
H61.51350.47860.04300.042*
C71.2412 (3)0.4433 (2)0.13602 (16)0.0295 (5)
C81.1581 (3)0.2248 (3)0.22061 (16)0.0309 (5)
C91.1809 (4)0.0669 (3)0.2550 (2)0.0413 (6)
H9A1.26780.05650.32970.050*
H9B1.25320.00980.19460.050*
C100.9409 (4)0.0170 (3)0.2667 (2)0.0428 (6)
H10A0.93070.05600.32970.051*
H10B0.87950.02610.19310.051*
C110.8183 (3)0.1590 (3)0.29605 (17)0.0351 (5)
H110.66530.15870.25900.042*
C120.8108 (4)0.1795 (3)0.42708 (19)0.0387 (6)
C130.6211 (4)0.1044 (4)0.5926 (2)0.0562 (8)
H13A0.76920.11470.63220.067*
H13B0.55730.01020.61690.067*
C140.4776 (5)0.2258 (4)0.6279 (2)0.0595 (7)
H14A0.33110.21580.58860.089*
H14B0.54330.31930.60630.089*
H14C0.46360.22280.71230.089*
N10.9521 (3)0.2705 (2)0.24410 (14)0.0315 (4)
N21.3078 (3)0.3013 (2)0.17238 (15)0.0328 (4)
O10.6431 (3)0.1034 (2)0.46705 (14)0.0454 (4)
O20.9396 (3)0.2508 (3)0.48572 (14)0.0652 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0276 (11)0.0351 (13)0.0405 (11)0.0037 (10)0.0048 (9)0.0020 (10)
C20.0287 (10)0.0315 (12)0.0298 (10)0.0010 (9)0.0006 (8)0.0023 (9)
C30.0340 (11)0.0361 (12)0.0380 (11)0.0045 (10)0.0007 (9)0.0005 (10)
C40.0511 (14)0.0309 (12)0.0383 (11)0.0021 (11)0.0026 (10)0.0044 (11)
C50.0450 (12)0.0389 (13)0.0316 (11)0.0062 (11)0.0036 (9)0.0033 (10)
C60.0296 (10)0.0399 (13)0.0351 (11)0.0049 (10)0.0042 (9)0.0039 (11)
C70.0276 (10)0.0320 (12)0.0285 (10)0.0003 (9)0.0014 (8)0.0011 (9)
C80.0282 (10)0.0337 (11)0.0307 (10)0.0034 (10)0.0013 (8)0.0002 (9)
C90.0376 (12)0.0370 (14)0.0495 (14)0.0034 (11)0.0055 (10)0.0055 (10)
C100.0451 (14)0.0366 (13)0.0471 (13)0.0041 (11)0.0065 (11)0.0043 (11)
C110.0279 (10)0.0412 (13)0.0361 (11)0.0061 (10)0.0011 (8)0.0062 (10)
C120.0308 (11)0.0479 (15)0.0372 (11)0.0032 (10)0.0001 (9)0.0092 (10)
C130.0580 (16)0.073 (2)0.0391 (13)0.0063 (16)0.0170 (12)0.0200 (14)
C140.0631 (16)0.0670 (18)0.0495 (14)0.0021 (16)0.0120 (12)0.0016 (15)
N10.0274 (9)0.0328 (11)0.0347 (9)0.0008 (8)0.0050 (7)0.0042 (8)
N20.0260 (9)0.0347 (11)0.0380 (9)0.0017 (8)0.0046 (7)0.0019 (8)
O10.0442 (9)0.0514 (11)0.0418 (9)0.0038 (8)0.0140 (7)0.0093 (8)
O20.0519 (11)0.1046 (18)0.0385 (9)0.0257 (12)0.0036 (8)0.0003 (11)
Geometric parameters (Å, º) top
C1—N11.452 (3)C9—C101.536 (3)
C1—C21.509 (3)C9—H9A0.9900
C1—H1A0.9900C9—H9B0.9900
C1—H1B0.9900C10—C111.541 (4)
C2—C31.383 (3)C10—H10A0.9900
C2—C71.403 (3)C10—H10B0.9900
C3—C41.387 (3)C11—N11.450 (3)
C3—H30.9500C11—C121.524 (3)
C4—C51.387 (3)C11—H111.0000
C4—H40.9500C12—O21.199 (3)
C5—C61.381 (3)C12—O11.332 (3)
C5—H50.9500C13—O11.459 (3)
C6—C71.394 (3)C13—C141.480 (4)
C6—H60.9500C13—H13A0.9900
C7—N21.416 (3)C13—H13B0.9900
C8—N21.293 (3)C14—H14A0.9800
C8—N11.355 (3)C14—H14B0.9800
C8—C91.502 (3)C14—H14C0.9800
N1—C1—C2108.86 (17)C9—C10—C11103.7 (2)
N1—C1—H1A109.9C9—C10—H10A111.0
C2—C1—H1A109.9C11—C10—H10A111.0
N1—C1—H1B109.9C9—C10—H10B111.0
C2—C1—H1B109.9C11—C10—H10B111.0
H1A—C1—H1B108.3H10A—C10—H10B109.0
C3—C2—C7119.57 (19)N1—C11—C12111.57 (19)
C3—C2—C1121.18 (19)N1—C11—C10102.49 (17)
C7—C2—C1119.23 (18)C12—C11—C10111.05 (18)
C2—C3—C4121.1 (2)N1—C11—H11110.5
C2—C3—H3119.5C12—C11—H11110.5
C4—C3—H3119.5C10—C11—H11110.5
C5—C4—C3119.5 (2)O2—C12—O1125.1 (2)
C5—C4—H4120.2O2—C12—C11125.0 (2)
C3—C4—H4120.2O1—C12—C11109.86 (19)
C6—C5—C4119.9 (2)O1—C13—C14111.2 (2)
C6—C5—H5120.0O1—C13—H13A109.4
C4—C5—H5120.0C14—C13—H13A109.4
C5—C6—C7121.0 (2)O1—C13—H13B109.4
C5—C6—H6119.5C14—C13—H13B109.4
C7—C6—H6119.5H13A—C13—H13B108.0
C6—C7—C2118.89 (19)C13—C14—H14A109.5
C6—C7—N2118.26 (19)C13—C14—H14B109.5
C2—C7—N2122.80 (18)H14A—C14—H14B109.5
N2—C8—N1126.3 (2)C13—C14—H14C109.5
N2—C8—C9125.2 (2)H14A—C14—H14C109.5
N1—C8—C9108.43 (19)H14B—C14—H14C109.5
C8—C9—C10103.55 (19)C8—N1—C11113.89 (18)
C8—C9—H9A111.0C8—N1—C1121.87 (18)
C10—C9—H9A111.1C11—N1—C1122.40 (17)
C8—C9—H9B111.1C8—N2—C7115.34 (18)
C10—C9—H9B111.1C12—O1—C13116.7 (2)
H9A—C9—H9B109.0
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5—H5···N2i0.952.593.523 (3)169
Symmetry code: (i) x+3, y+1/2, z.

Experimental details

Crystal data
Chemical formulaC14H16N2O2
Mr244.29
Crystal system, space groupMonoclinic, P21
Temperature (K)187
a, b, c (Å)6.0545 (8), 9.1438 (13), 11.5228 (16)
β (°) 92.905 (2)
V3)637.10 (15)
Z2
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.29 × 0.22 × 0.19
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
3430, 1246, 1166
Rint0.016
(sin θ/λ)max1)0.602
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.031, 0.076, 1.08
No. of reflections1246
No. of parameters164
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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···AD—HH···AD···AD—H···A
C5—H5···N2i0.952.593.523 (3)169
Symmetry code: (i) x+3, y+1/2, z.
 

References

First citationBruker (1997). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationBruker (1999). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationCheng, 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
First citationHua, 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
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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ISSN: 2056-9890
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