Triethylamine → 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

Participants

Reaction Steps

To a solution of 3-(benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylic acid, Intermediate 4 (180 mg, 0.368 mmol) in CH2Cl2 (2 mL) was added oxalyl chloride (0.051 mL, 0.588 mmol) followed by 1 drop of DMF. After stirring for 2 h, the mixture was concentrated under reduced pressure. The crude acid chloride was then diluted with dichloromethane (2 mL) and added to a stirred solution of 2-amino-3-(4-fluorophenyl)propanenitrile HCl (81 mg, 0.404 mmol) and triethylamine (0.205 mL, 1.471 mmol) in CH2Cl2 (2 mL) and the resulting solution was stirred at room temperature. After 16 h at room temperature, the reaction mixture was poured into sat. NaHCO3 and extracted with dichloromethane (50 mL×3), dried (Na2SO4), filtered and concentrated to give a yellow oil. The crude product was then purified by silica gel chromatography (50-100% EtOAc/hexane) to afford the title compound (145 mg, 62% yield) as a light yellow solid. 1H NMR (500 MHz, CDCl3) δ: 7.82 (brs, 1H), 7.28-7.49 (m, 10H), 7.06-7.17 (m, 2H), 6.96 (t, 2H, J=8.39 Hz), 6.63 (brs, 1H), 5.27-5.40 (m, 2H), 5.00-5.14 (m, 2H), 4.07-4.14 (m, 3H), 2.77-2.92 (m, 2H), 2.64-2.78 (m, 2H), 2.49 (brs, 1H), 1.87-2.02 (m, 4H), 1.63-1.75 (m, 2H). LCMS (M+H)=636.19.

Provenance & Evidence