1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl(s)-1-((3ar,4s,6as)-4-(2,2-bis(4-fluorophenyl)acetamido)hexahydrocyclopenta[c]pyrrol-2(1h)-yl)-4-methyl-1-oxopentan-2-yl(methyl)carbamate

Participants

Reaction Steps

2,2-Bis(4-fluorophenyl)-N-[(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-yl]acetamide (30 mg, 0.084 mmol) and (S)-2-(tert-butoxycarbonyl(methyl)amino)-4-methylpentanoic acid (22.71 mg, 0.093 mmol) were dissolved in dichloromethane (0.5 mL) and then treated with 1-hydroxybenzotriazole hydrate (14.18 mg, 0.093 mmol). After 10 minutes, N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.016 mL, 0.093 mmol) was added, and the reaction mixture was stirred at ambient temperature overnight followed by quenching with water. The material in the organic layer was purified with a 4 g silica gel cartridge eluting with 1-10% methanol (2 N ammonia)/dichloromethane to give tert-butyl(S)-1-((3aR,4S,6aS)-4-(2,2-bis(4-fluorophenyl)acetamido)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-4-methyl-1-oxopentan-2-yl(methyl)carbamate: 1H NMR (400 MHz, pyridine-d5) δ ppm 8.25 (s, 1H), 7.46 (td, J=8.5, 5.5, 4H), 7.08-6.96 (m, 4H), 5.08 (s, 2H), 4.29-4.18 (m, 1H), 3.80 (s, 2H), 3.69 (s, 1H), 3.43 (dd, J=11.7, 3.5, 1H), 2.93 (s, 3H), 2.63 (s, 2H), 2.10 (td, J=12.9, 6.9, 1H), 1.91-1.69 (m, 3H), 1.63 (dt, J=13.2, 6.5, 2H), 1.51 (s, 9H), 1.40-1.26 (m, 1H), 0.97 (d, J=6.5, 3H), 0.92 (d, J=6.6, 3H); MS (ESI+) m/z 584 (M+H)+.

Provenance & Evidence