4-Methylmorpholine → tert-butyl (R)-4-((R)-3-(1-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

Participants

Reaction Steps

(R)-2-(2-(2-(piperidin-3-yl)-1H-benzo[d]imidazol-1-yflethypisoindoline-1,3-dione (129B) (500 mg of mixture) from previous step, was weighed into a 25 mL round-bottomed flask equipped for stirring under nitrogen. DMF (3 mL), (R)-3-(tert-butoxycarbonylamino)-4-(naphthalen-2-yl)butanoic acid (2.48 mmoles, 0.817 g) and N-methylmorpholine (7.44 mmoles, 0.818 mL) were then added and the solution was allowed to stir at rt for 5 min. HATU (2.73 mmoles, 1.04 g) was added and the resultant solution was stirred at room temperature for 3 hrs. The reaction solution was then directly purified by preparative LC/MS (35-95% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording tert-butyl (R)-4-((R)-3-(1-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (129C) as a clear oil. (0.105 mmoles, 0.072 g, 4% yield over 2-steps). ESI-MS: m/z 686.5 (M+H)+.

Provenance & Evidence