反应详情

Triethylamine (360 μl, 2.58 mmol) was added to a stirred, cooled (0° C.) suspension of 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide (300 mg, 0.63 mmol) (Example 16) in NMP (5 ml). Acetoxyacetyl chloride (100 μl 0.93 mmol) was then added drop wise and the reaction mixture left to warm to room temperature over a period of 2 hours. This was then partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic phase was washed with saturated aqueous ammonium chloride solution followed by brine, dried over magnesium sulfate, filtered and evaporated to give 2-{4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidin-1-yl}-2-oxoethyl acetate as a dry film (250 mg). Mass spectrum: (M+H)+ 573.

1. temperaturecooled
2. waitthe reaction mixture left
3. customThis was then partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
4. washThe organic phase was washed with saturated aqueous ammonium chloride solution
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customevaporated