4-Methylmorpholine → tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

Participants

Reaction Steps

The crude (1S,3aR,6aS)-2-((S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid from Example 10 was dissolved in dichloromethane (4 mL) and treated with 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (EDCI) (71 mg, 2 eq), 1-hydroxybenzotriazole (HOBT) (57 mg, 2 eq) and N-methyl morpholine (0.2 mL, 5 eq) at room temperature. To this mixture was added after 30 minutes (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide, the compound of formula (12) (1 eq) in dichloromethane (3 mL) and N,N-dimethylformamide (3 mL) and the reaction mixture was stirred at room temperature. After 18 hours the reaction mixture was diluted with water, and the product extracted into ethyl acetate. The organic extract was washed with brine, dried and evaporated to dryness under reduced pressure, to give crude tert-butyl (2S)-1-((1S,3aR,6aS)-1-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-ylcarbamoyl)hexahydrocyclopenta-[c]pyrrol-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate, the compound of formula (17).

Provenance & Evidence