反应详情

To a solution of racemic 1-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-N,N,4,4-tetramethyl-3-pyrrolidinamine (7.37 g, 24.34 mmol, prepared according to the procedures of Example 133) in DMF (77 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (7.08 g, 23.18 mmol), N-methylmorpholine (12.75 mL, 116.0 mmol), 1-hydroxy-7-azabenzotriazole (3.79 g, 27.85 mmol), and EDC (5.33 g, 27.80 mmol). The solution was stirred overnight and was then diluted with Et2O (100 mL) and washed with water (3×100 mL). The combined aqueous phase was extracted with a fresh portion of Et2O (100 mL), and this organic phase was washed with a fresh portion of water (50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was diluted with EtOAc (200 mL), and the resulting solution was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford crude [(2R)-3-(2-{2-chloro-6-[4-(dimethylamino)-3,3-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (12.52 g, 92% yield, mixture of diastereomers). LCMS: (M+H)+: 590.2.

1. washwashed with water (3×100 mL)
2. extractionThe combined aqueous phase was extracted with a fresh portion of Et2O (100 mL)
3. washthis organic phase was washed with a fresh portion of water (50 mL)
4. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. additionThe residue was diluted with EtOAc (200 mL)
8. dry with materialthe resulting solution was dried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo