7-Benzyl-3-(4-fluoro­phen­yl)-2-propyl­amino-5,6,7,8-tetra­hydro­pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one

Hai-Jun Hu; Hong Chen

doi:10.1107/S1600536812010318

. 2012 Mar 17;68(Pt 4):o1097. doi: 10.1107/S1600536812010318

7-Benzyl-3-(4-fluorophenyl)-2-propylamino-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one

Hai-Jun Hu ^a, Hong Chen ^b,^*

PMCID: PMC3344049 PMID: 22589958

Abstract

In the title compound, C₂₅H₂₅FN₄OS, the thienopyrimidine fused-ring system is close to planar (r.m.s. deviation = 0.0089 Å), with a maximum deviation of 0.0261 (17) Å for the N atom adjacent to the benzene ring. This thienopyrimidine fused-ring system forms dihedral angles of 64.73 (3) and 81.56 (5)° with the adjacent benzyl and fluorophenyl rings, respectively. Intermolecular N—H⋯F and C—H⋯F hydrogen bonding, as well as C—F⋯π interactions [F⋯centroid = 3.449 (3) Å; C—F⋯centroid = 91.87 (15)°], help to stabilize the crystal structure.

Related literature

For the biological and pharmaceutical properties of compounds containing the fused thienopyrimidine system, see: Amr et al. (2010 ▶); Huang et al. (2009 ▶); Mavrova et al. (2010 ▶). For similar crystal structures, see: Xie et al. (2008) ▶; Chen et al. (2011 ▶).

Experimental

Crystal data

C₂₅H₂₅FN₄OS
M _r = 448.55
Orthorhombic,
a = 17.921 (7) Å
b = 18.427 (7) Å
c = 27.114 (10) Å
V = 8954 (6) Å³
Z = 16
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 296 K
0.26 × 0.25 × 0.23 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.955, T _max = 0.960
46089 measured reflections
5152 independent reflections
4234 reflections with I > 2σ(I)
R _int = 0.107

Refinement

R[F ² > 2σ(F ²)] = 0.069
wR(F ²) = 0.194
S = 1.05
5152 reflections
290 parameters
H-atom parameters constrained
Δρ_max = 0.58 e Å⁻³
Δρ_min = −0.30 e Å⁻³

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

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812010318/gw2115sup1.cif

e-68-o1097-sup1.cif^{(23.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812010318/gw2115Isup2.hkl

e-68-o1097-Isup2.hkl^{(252.6KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812010318/gw2115Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C24—H24B⋯F1ⁱ	0.97	2.66	3.258 (5)	121
C25—H25A⋯F1ⁱ	0.96	2.56	3.096 (5)	116
N4—H4A⋯F1ⁱ	0.86	2.65	3.423 (3)	151

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported financially by the National Natural Science Foundation of China (project No. 21102084), the Key Project of Hubei Provincial Department of Education, China (project No. D20091301) and the Doctoral Start-up Foundation of China Three Gorges University (project No. KJ2009B004).

supplementary crystallographic information

Comment

Derivatives of heterocycles containing the thienopyrimidine system have proved to show significant antifungal, antibacterical, anticonvulsant and angiotensin antagonistic activities (Amr et al. 2010; Huang et al. 2009; Mavrova et al. 2010). Recently, we have focused on the synthesis of fused heterocyclic systems containing thienopyrimidine via aza-wittig reaction under mild conditions. Some X-ray crystal structures of fused pyrimidinone derivatives have been reported (Chen et al., 2011; Xie et al., 2008). The title compound has potential use as a precursor for obtaining bioactive molecules with fluorescence properties. Herein, we report its crystal structure (Fig. 1).

In the crystal structure of the title compound, C₂₅H₂₅FN₄OS, the thienopyrimidine fused-ring system is close to coplanar (r.m.s deviation = 0.0089 Å) with a maximum deviation of -0.0261 (17) Å for atom N(3). This ring system forms diherdral angles of 64.73 (3) and 81.56 (5)° with the adjacent 6-membered rings C1—C6 and C17—C22, respectively. Most bond lengths in the system fell in the range of single and double bonds, for example, the bond lengths of C(9)—C(10), C(13)—C(14) and C(16)—O(1) were in accordance with the double bond distances. Intermolecular N—H···F (N4—H4A···F1ⁱ with symmetry code: (i) 3/2 - x, y, -z) and C—H···F hydrogen bonding (C24—H24B···F1ⁱ and C25—H25A···F1ⁱ), as well as C—F···π interactions (C20—F1···Cg1 with Cg1 centroids of the C17—C18—C19—C20—C21 ring), helps to stabilize the crystal structure.

Experimental

1-fluoro-4-isocyanatobenzene (2 mmol) under nitrogen atmosphere was added to a solution of iminophosphorane (2 mmol) in anhydrous CH₂Cl₂ (10 ml) at room temperature. When the reaction mixture was left unstirred for 12 h at 273–278 k, iminophosphorane was consumed (TLC monitored). The solvent was removed under reduced pressure and ether/petroleum ether (volume ratio 1:2, 20 ml) was added to precipitate triphenylphosphine oxide. Removal of the solvent gave carbodiimide, which was used directly without further purification. Propan-1-amine (2 mmol) was added to the solution of carbodiimide in anhydrous dichloromethane (10 ml). After the reaction mixture was left unstirred for 5–6 h, the solvent was removed and anhydrous EtOH (10 ml) with several drops of EtONa (in EtOH) was added to the mixture. The mixture was stirred for another 6–8 h at room temperature. The solution was condensed and the residual was recrystallized from EtOH to give the expected title compound as white crystals, 0.832 g (87%), M.p. 431–432 K; ¹H NMR (CDCl₃, 600 MHz) δ: 7.37–7.25 (m, 9H, Ar—H), 4.06 (br, 1H, NH), 3.72 (s, 2H, Ar—CH₂), 3.59 (s, 2H, NCH₂-thiophene), 3.31 (m, 2H, NHCH₂), 2.98 (t, J = 5.1 Hz, 2H, NCH₂CH₂), 2.82 (t, J = 5.1 Hz, 2H, NCH₂CH₂), 1.50–1.48 (m, 2H, CH₂CH₃), 0.84 (t, J = 6.6 Hz, 3H, CH₂CH₃); IR (KBr) v: 3373 (N—H), 1673 (C=O), 1540, 1378, 696 cm^-1; EI—MS m/z (%): 448 (M⁺, 15), 357 (16), 329 (100), 287 (26), 91 (72). Anal. calcd for C₂₅H₂₅FN₄OS: C 66.94, H 5.62, N 12.49; found: C 66.71, H 5.50, N 12.23.