反应详情

EDC (0.104 g, 0.54 mmol), HOAt (24.6 mg, 0.18 mmol), NMM (0.079 mL, 0.72 mmol), and N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-L-prolinamide hydrochloride (Example 26, Step B, 0.143 g, 0.42 mmol) were added to a stirred solution of racemic 1-(tert-butoxycarbonyl)-2-methylazetidine-2-carboxylic acid (0.143 g, 0.36 mmol in DMF (1.1 mL). After 3 h at room temperature the reaction was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo. The two diastereomers were separated and purified by reverse phase HPLC. The more polar diastereomer was concentrated in vacuo. N-[5-chloro-2-(1H-tetraazol-1-yl)benzyl]-1-[(1-tert-butoxycarbonyl-2-methylazetidin-2-yl)carbonyl]-L-prolinamide (diastereomer A) was obtained as a glass. MS m/z=404.6).

1. customAfter 3 h at room temperature the reaction was partitioned between EtOAc and water
2. washThe organic layer was washed with brine
3. dry with materialdried (Na2SO4)
4. concentrationconcentrated in vacuo
5. customThe two diastereomers were separated
6. custompurified by reverse phase HPLC
7. concentrationThe more polar diastereomer was concentrated in vacuo