反应详情

To a solution of (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid, N,N-diisopropylethylamine salt, isopropanol solvate (33.64 g, 68.0 mmol) in DMF (230 mL) was added (9aS)-8-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazine (20.16 g, 71.4 mmol), N-methylmorpholine (30 mL, 273 mmol), 1-hydroxy-7-azabenzotriazole (11.10 g, 81.6 mmol), and EDC (15.64 g, 81.6 mmol). The solution was stirred overnight and then diluted with Et2O (500 mL). The mixture was washed with water (2×200 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (100 mL). This Et2O phase was then washed with water (50 mL). This extraction-wash procedure was repeated 6 times, and the total combined organic phase was then diluted with DCM (250 mL). The organic phase was then dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give crude [(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 (42.32 g, >100% crude yield) as a light yellow foam. LCMS: (M+H)+: 570.3.

1. washThe mixture was washed with water (2×200 mL)
2. extractionthe combined aqueous phase was extracted with a fresh portion of Et2O (100 mL)
3. washThis Et2O phase was then washed with water (50 mL)
4. additionthe total combined organic phase was then diluted with DCM (250 mL)
5. dry with materialThe organic phase was then dried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo