反应详情

A solution of (2S,3S,5R)-2-benzyl-3-benzylamino-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (0.16 mmol; 61 mg) in ethanol (5 mL) is hydrogenated over 10% palladium on carbon (6 mg) at 50° C. and atmospheric pressure. After 9.5 hours, the suspension is cooled to ambient temperature and purged with nitrogen. The reaction mixture is filtered and concentrated under reduced pressure. A mixture of the obtained material (46 mg), 5-bromo-2-chloropyrimidine (0.18 mmol; 34.8 mg) and DIPEA (0.32 mmol; 41.4 mg) in DMF (0.8 mL) is stirred at 100° C. for 4 hours and then at 120° C. for 8.5 hours, and cooled to ambient temperature. The solution is diluted with brine and EtOAc. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (n-hexane/EtOAc) to give (2S,3S,5R)-2-benzyl-3-(5-bromo-pyrimidin-2-ylamino)-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (28.6 mg, 40% in 2 steps); ESI-MS m/z: 447 [M++1], Retention time 2.36 min (condition A).

1. custompurged with nitrogen
2. filtrationThe reaction mixture is filtered
3. concentrationconcentrated under reduced pressure
4. waitat 120° C. for 8.5 hours
5. temperaturecooled to ambient temperature
6. extractionThe product is extracted three times with EtOAc
7. washThe combined organic layer is washed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue is purified by column chromatography on silica gel (n-hexane/EtOAc)