7-Benzyl-3-(4-fluoro­phen­yl)-2-(pyrrol­idin-1-yl)-5,6,7,8-tetra­hydro­pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one

Hong Chen; Hai-Jun Hu; Kai Yan; Qiu-Hong Dai

doi:10.1107/S1600536811030625

. 2011 Aug 2;67(Pt 9):o2228. doi: 10.1107/S1600536811030625

7-Benzyl-3-(4-fluorophenyl)-2-(pyrrolidin-1-yl)-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one

Hong Chen ^a,^*, Hai-Jun Hu ^b, Kai Yan ^b, Qiu-Hong Dai ^b

PMCID: PMC3200784 PMID: 22065028

Abstract

In the title compound, C₂₆H₂₅FN₄OS, the thienopyrimidine fused-ring system is close to planar (r.m.s. deviation = 0.066 Å), with a maximum deviation of 0.1243 (17) Å for the N atom adjacent to the carbonyl group. This ring system forms dihedral angles of 67.5 (1) and 88.9 (1) ° with the adjacent six-membered rings. Intermolecular C—H⋯O hydrogen bonding and C—H⋯π interactions 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 ▶); Jennings et al. (2005 ▶); Kikuchi et al. (2006 ▶); Mavrova et al. (2010 ▶); Santagati et al. (2002 ▶). For related structures, see: Hu et al. (2007 ▶); Xie et al. (2008 ▶).

Experimental

Crystal data

C₂₆H₂₅FN₄OS
M _r = 460.56
Triclinic,
a = 8.132 (10) Å
b = 9.736 (11) Å
c = 15.540 (18) Å
α = 99.742 (16)°
β = 99.636 (11)°
γ = 105.551 (14)°
V = 1139 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.18 mm⁻¹
T = 296 K
0.23 × 0.20 × 0.15 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.960, T _max = 0.974
12210 measured reflections
5233 independent reflections
4018 reflections with I > 2σ(I)
R _int = 0.154

Refinement

R[F ² > 2σ(F ²)] = 0.064
wR(F ²) = 0.180
S = 1.05
5233 reflections
298 parameters
H-atom parameters constrained
Δρ_max = 0.48 e Å⁻³
Δρ_min = −0.38 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/S1600536811030625/zq2114sup1.cif

e-67-o2228-sup1.cif^{(24.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811030625/zq2114Isup2.hkl

e-67-o2228-Isup2.hkl^{(256.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811030625/zq2114Isup3.cml

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

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

Cg1 and Cg2 are the centroids of the S1-C11-C10-C13-C16 and N2-C15-N3-C14-C13-C16 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8B⋯O1ⁱ	0.97	2.50	3.461 (5)	171
C24—H24B⋯O1ⁱⁱ	0.97	2.44	3.316 (5)	151
C25—H25B⋯Cg1ⁱⁱⁱ	0.97	2.86	3.693 (5)	144
C26—H26B⋯Cg2ⁱⁱⁱ	0.97	2.80	3.717 (5)	158

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was supported financially by the Science Foundation of Hubei Province Education Department, China (project No. D20091301) and the Excellent Fund for Scientific Research and Special Projects in China Three Gorges University, China (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; Jennings et al. 2005; Kikuchi et al. 2006; Mavrova et al. 2010; Santagati et al. 2002). 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 (Hu et al., 2007; 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 and 2).

In the crystal structure of the title compound, C₂₆H₂₅FN₄OS, the thienopyrimidine fused ring system are essentially coplanar (rms deviation = 0.066 Å) with a maximum deviation of 0.1243 (17) Å for atom N3. This ring system forms dihedral angles of 67.5 (1) and 88.9 (1) ° with the adjacent 6-membered rings C17–C22 and C1-C6, respectively. Intermolecular C—H···O hydrogen bondings (C8—H8B···O1ⁱ and C24—H24B···O1ⁱⁱ with symmetry codes: (i) -x+2, -y, -z+1; (ii) x-1, y, z) and C—H···π interactions (C25—H25B···Cg1ⁱⁱⁱ and C26—H26···Cg2ⁱⁱⁱ with Cg1 and Cg2 centroids of the S1-C11-C10-C13-C16 and N2-C15-N3-C14-C13-C16 rings and symmetry code: (iii) 1-x, 1-y, 1-z) help to stabilize the crystal structure of the title compound (Table 1).

Experimental

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 (Fig. 3). When the reaction mixture was left unstirred for 12 h at 273–278k, 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. Pyrrolidine (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.