反应详情

To a stirred solution of N-[5-chloro-2-(1H1,2,4-triazol-1-yl)benzyl]-L-prolinamide (Example 27, Step B, 0.046 g, 0.121 mmol), N-(tert-butoxycarbonyl)-3-cyclopropyl-D-alanine (30 mg, 0.121 mmol), and HOBt hydrate (20 mg, 0.145 mmol) in DMF (3 mL) was added EDC (0.028 g, 0.145 mmol). Diisopropylethylamine (0.083 mL, 0.484 mmol) was added and the mixture was stirred at ambient temperature for 18 hours, at which time HPLC analysis indicated complete consumption of the proline starting material. The DMF was removed under reduced pressure and the residue was partitioned between EtOAc (50 mL) and 10% aqueous Na2CO3. The EtOAc layer was separated, washed with water and brine, dried over anhydrous MgSO4, and filtered. The filtrate solvent was removed under reduced pressure to give N-(tert-butoxycarbonyl)-3-cyclopropyl-D-alanyl-N-[5-chloro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide as a gum (0.058 g). HPLC RT=2.18 min, Method B; LCMS (M+H): 517, 519.

1. customconsumption of the proline starting material
2. customThe DMF was removed under reduced pressure
3. customthe residue was partitioned between EtOAc (50 mL) and 10% aqueous Na2CO3
4. customThe EtOAc layer was separated
5. washwashed with water and brine
6. dry with materialdried over anhydrous MgSO4
7. filtrationfiltered
8. customThe filtrate solvent was removed under reduced pressure