反应详情

To a solution of [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide (assumed 38.74 g, 68.0 mmol) in methanol (225 mL) was added 10% Pd/C (5.81 g). The mixture was hydrogenated under balloon pressure for 4 h, and was then filtered through a glass fiber filter with MeOH washes. The resulting solution was concentrated in vacuo to approximately 10% volume, diluted with EtOAc (400 mL), and concentrated in vacuo to approximately 30% volume. The resulting solid was collected by vacuum filtration and washed with EtOAc. The mother liquor and EtOAc washings were concentrated in vacuo to approximately 10% volume, and the resulting solid was collected by vacuum filtration and washed with EtOAc. The two crops of solid were combined and dried at 50° C. for 16 h under high vacuum to afford [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl]hydroxyformamide (25.48 g, 78% yield for 2 steps) as a white solid. LCMS: (M+H)+: 480.1.

1. filtrationwas then filtered through a glass fiber
2. filtrationfilter with MeOH washes
3. concentrationThe resulting solution was concentrated in vacuo to approximately 10% volume
4. additiondiluted with EtOAc (400 mL)
5. concentrationconcentrated in vacuo to approximately 30% volume
6. filtrationThe resulting solid was collected by vacuum filtration
7. washwashed with EtOAc
8. concentrationThe mother liquor and EtOAc washings were concentrated in vacuo to approximately 10% volume
9. filtrationthe resulting solid was collected by vacuum filtration
10. washwashed with EtOAc
11. customdried at 50° C. for 16 h under high vacuum