Triethylamine → 4-allyl-5,6-difluoro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 5.0 g (13.289 mmol) N-[3,4-difluoro-2-(4-fluorobenzoyl)phenyl]-N′-(2,2,2-trifluoroethyl)urea (open form) and 5,6-difluoro-4-(4-fluorophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (closed form) in 25 ml THF was added 9.261 mL (66.443 mmol) triethylamine. After 1 h at 80° C., the reaction mixture was cooled to −78° C. To this solution was added 0.969 mL (13.289 mmol) thionyl chloride. After 30 mins at −78° C., 45 mL (41.195 mmol) allylmagnesium bromide (1.0M solution in dibutyl ether) was added dropwise. After 30 minutes at −78° C., the reaction mixture was quenched with saturated NH4Cl and warmed to room temperature. The reaction mixture was extracted three times with EtOAc and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (1×14 cm silica gel, linear gradient 0-35% EtOAc:hexane) afforded 4-allyl-5,6-difluoro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one. 1H NMR (CDCl3, 400 MHz) δ 7.46 (br s, 1H, ArNHC═O); 7.42-7.40 (m, 2H, ArH); 7.10-7.00 (m, 3H, ArH); 6.44 (m, 1H, ArH); 5.73-5.66 (m, 1H, CH2CH═CH2); 5.13-5.09 (m, 2H, CH2CH═CH2); 3.73 (m, 2H, NCH2CF3); 3.15 (m, 2H, CH2CH═CH2). HRMS (ES) exact mass calcd for C19H14F6N2O: 401.1083, Found: 401.1075.

Provenance & Evidence