Carbon Tetrachloride → benzyl(3-(benzyloxy)-2-(4-chloro-5-(4-fluorobenzyl)-1H-imidazol-2-yl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of benzyl(3-(benzyloxy)-2-((1-cyano-2-(4-fluorophenyl)ethyl)carbamoyl)-4-oxo-6,7,8,9-tetrahydro-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl)carbamate, Intermediate 5 (140 mg, 0.220 mmol) in acetonitrile (4 mL) was added carbon tetrachloride (0.053 mL, 0.551 mmol), followed by triphenylphosphine (144 mg, 0.551 mmol) and the mixture was heated at 45° C. After stirring for 16 h, the mixture was cooled to room temp and concentrated in vacuo. The residue was then treated with dichloromethane (10 mL) and 0.5 N NaOH (20 mL). The mixture was then poured into water and extracted with dichloromethane (×4), dried (Na2SO4), filtered and concentrated. The crude product was then purified by silica gel chromatography (40-100% EtOAc/hexane) to afford the title compound (90 mg, 42% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 1.65-1.74 (m, 2H) 1.92-2.03 (m, 4H) 2.47 (br. s., 1H) 2.71-2.86 (m, 2H) 3.74 (s, 2H) 4.13 (d, J=3.66 Hz, 2H) 5.12 (s, 2H) 5.29 (s, 2H) 6.92 (d, J=7.63 Hz, 4H) 7.08 (br. s., 1H) 7.29-7.37 (m, 8H) 7.39-7.46 (m, 2H) 10.08 (br. s., 1H). (M+H)=654.28.

Provenance & Evidence