反应详情

1-((3aR,4S,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-methyl-2-phenylbutan-1-one hydrochloric acid salt (49 mg, 0.152 mmol) and benzaldehyde (0.023 mL, 0.228 mmol) were combined in dichloromethane (1.5 mL). Acetic acid (1.5 mL) was added. The reaction was stirred at room temperature for 30 minutes, then PS-cyanoborohydride (64.9 mg, 0.152 mmol) was added. After 72 hours, LCMS of the reaction showed no more starting material. The reaction mixture was filtered, and the solvent was removed under a stream of nitrogen. The crude material was purified using a silica gel cartridge (Analogix®, Burlington, Wis., RS-4) eluting with 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.69-7.60 (m, 2H), 7.54-7.44 (m, 2H), 7.44-7.34 (m, 5H), 7.29 (tdd, J=4.8, 7.8, 13.0, 2H), 3.90-3.36 (m, 4H), 3.29 (dd, J=3.8, 10.6, 0.5H), 2.99 (dd, J=5.7, 11.4, 0.5H), 2.93 (dd, J=6.0, 11.3, 0.5H), 2.75-2.63 (m, 1H), 2.59-2.48 (m, 1H), 2.46-2.31 (m, 1H), 2.25 (dt, J=4.1, 8.7, 0.5H), 1.97 (dt, J=9.3, 11.6, 1H), 1.93-1.85 (m, 0.5H), 1.84-1.74 (m, 1H), 1.65-1.55 (m, 0.5H), 1.51-1.35 (m, 1H), 1.33-1.21 (m, 1H), 1.18-1.10 (m, 3H), 1.01 (td, J=7.7, 13.1, 0.5H), 0.87 (dt, J=6.6, 12.9, 0.5H), 0.75 (t, J=7.2, 3H); MS (ESI+) m/z 377 (M+H)+.

1. waitAfter 72 hours
2. filtrationThe reaction mixture was filtered
3. customthe solvent was removed under a stream of nitrogen
4. customThe crude material was purified
5. washeluting with 1-10% methanol (2 N ammonia)/dichloromethane