反应详情

To a stirred solution of commercially-available [2-methyl-2-(4-morpholinyl)propyl]amine (0.158 g, 1.00 mmol) in DMF (10 mL) under a nitrogen atmosphere at 0° C., was added diisopropylethylamine (0.19 mL, 1.1 mmol) followed immediately by tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (0.497 g, 1.00 mmol). The reaction was allowed to reach room temperature and was stirred overnight. Then ether was added, and the mixture was washed with water. The aqueous layer was back extracted with ether, and the combined organics were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (5-60% ethyl acetate in hexanes, 1% triethylamine) to provide tris(1,1-dimethylethyl)2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate as a clear oil (0.578 g, 94%). LCMS: (M+H)+=619.4.

1. customto reach room temperature
2. washthe mixture was washed with water
3. extractionThe aqueous layer was back extracted with ether
4. dry with materialthe combined organics were dried (Na2SO4)
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by silica gel chromatography (5-60% ethyl acetate in hexanes, 1% triethylamine)