4-Methylmorpholine → tert-butyl (R)-4-((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

Participants

Reaction Steps

(R)-6-Methoxy-1-(3-methoxypropyl)-2-(piperidin-3-yl)-1H-benzo[d]imidazole (41E) (2.82 mmol, 0.86 g) in DMF (16 mL) was added (R)-3-(tert-butoxycarbonylamino)-4-(naphthalen-2-yl)butanoic acid (3.10 mmol, 1.02 g) and N-methylmorpholine (11.28 mmol, 1.24 mL). The reaction mixture was stirred at rt for 5 min and then added HATU (3.10 mmol, 1.18 g) and kept stirring at rt overnight. The reaction mixture was poured into H2O, extracted with EtOAc. The extract was washed with H2O, NaHCO3, brine, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and purified by preparative LC/MS (40-90% CH3CN in H2O) to afford tert-butyl (R)-4-((R)-3-(6-methoxy-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (42F) (0.63 mmol, 0.387 g, three-step yield: 22.3%). ESI-MS: m/z 616.5 (M+H)+.

Provenance & Evidence