反应详情

To a solution of 4-[(2R)-2,4-dimethyl-1-piperazinyl]-5-fluoro-6-hydrazino-2-methylpyrimidine (8.04 g, assumed 31.4 mmol) in N,N-dimethylformamide (125 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid diisopropylethylamine salt, isopropanol solvate (15.48 g, 31.3 mmol), N-methylmorpholine (17.21 mL, 156 mmol), 1-hydroxy-7-azabenzotriazole (5.11 g, 37.6 mmol), and EDC (7.20 g, 37.6 mmol). The solution was stirred overnight, and then diluted with Et2O (150 mL) and washed with water (2×100 mL). The combined aqueous phase was extracted with a fresh portion of Et2O (150 mL), and this organic phase was washed with water (75 mL). The total combined aqueous phase was extracted with another fresh portion of Et2O (150 mL), and this organic phase was washed with water (75 mL). The combined organic phase was diluted with DCM (100 mL), and dried over anhydrous Na2SO4. The mixture was filtered and concentrated in vacuo to give crude [(2R)-2-(cyclopentylmethyl)-3-(2-{6-[(2R)-2,4-dimethyl-1-piperazinyl]-5-fluoro-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide (15.60 g, 28.8 mmol, 92% yield) as a light brown foam. LCMS: (M+H)+: 541.7.

1. washwashed with water (2×100 mL)
2. extractionThe combined aqueous phase was extracted with a fresh portion of Et2O (150 mL)
3. washthis organic phase was washed with water (75 mL)
4. extractionThe total combined aqueous phase was extracted with another fresh portion of Et2O (150 mL)
5. washthis organic phase was washed with water (75 mL)
6. additionThe combined organic phase was diluted with DCM (100 mL)
7. dry with materialdried over anhydrous Na2SO4
8. filtrationThe mixture was filtered
9. concentrationconcentrated in vacuo