Triethylamine → 6-chloro-4-phenyl-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a −78° C. mixture of 6-chloro-4-hydroxy-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one (214 mg, 0.6 mmol) and tetrahydrofuran (2.0 ml) was added triethylamine (0.4 ml, 3.1 mmol) under nitrogen atmosphere. After stirring mixture at −78° C. for 20 minutes, thionyl chloride (0.05 ml, 0.64 mmol) was added dropwise whereupon a yellow solid precipitated in the reaction mixture forming a thick yellow emulsion. After the emulsion was stirred at −78° C. for 30 minutes, 3.0M phenyl magnesium bromide was added. Reaction was allowed to stir for one hour until no further increase in desired product was observed by LC/MS. Reaction was quenched with saturated aqueous ammonium chloride solution (10 ml) at −78° C. and mixture was allowed to warm to room temperature. Mixture was extracted with ethyl acetate (3×20 ml) and combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The resulting crude oil was purified by flash chromatography on silica gel (0-30% ethyl acetate/hexanes) to afford an oil which was further purified by reverse phase prep HPLC to give 6-chloro-4-phenyl-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one as colorless oil. 1H NMR (CD3OD, 400 MHz) δ 7.52 (m, 5H), 7.34 (dd, J=2.4 and 8.4 Hz, 1H), 6.95 (d, J=8.4 Hz, 1H), 6.4 (m, 1H), 4.29 (m, 1H), 3.62 (m, 1H). Exact Mass (Electrospray, M+H): Calc'd, 409.0537; Found, 409.0533.

Provenance & Evidence