反应详情

To a solution of racemic N,N-dimethyl-3-azabicyclo[3.1.0]hexan-1-amine dihydrochloride (assumed 0.5339 g, 2.681 mmol) in DMF (13 mL) was added tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (1.33 g, 2.674 mmol) and N,N-diisopropylethylamine (1.87 mL, 10.74 mmol). The solution was stirred overnight and then diluted with Et2O (100 mL). The mixture was washed with water (2×50 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (50 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N) to afford racemic tris(1,1-dimethylethyl)2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (1.3261 g, 84%) as a white foam. LCMS: (M+H)+: 587.3.

1. washThe mixture was washed with water (2×50 mL)
2. extractionthe combined aqueous phase was extracted with a fresh portion of Et2O (50 mL)
3. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N)