反应详情

To a stirring solution of 1.2 g (3.5 mmol) of 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrile and 0.52 g (4.0 mmol) of diisopropylethylamine in 40 ml of tetrahydrofuran at 0° C. was added a solution of 4-bromo crotonyl chloride in 10 ml of tetrahydrofuran. After 45 min, 1.87 (21 mmol) of 2-methoxyethyl methyl amine was added. After 1 hr at room temperature, the mixture was poured into a solution of sodium bicarbonate and extracted with ethyl acetate. The organic solution was dried over magnesium sulfate. The solvent was removed and the residue was purified by chromatography on silica gel. Product eluted with ethyl acetate-methanol-triethylamine 40:8:1 giving 0.87 g of the free base. This was dissolved in 20 ml of ethyl acetate and 10 ml of a solution of hydrogen chloride in ether was added. The solid was collected giving 1.02 g of the title compound as a yellow powder: mass spectrum (electrospray, m/e): M+H 498.0, (M+2H)+2248.5.

1. waitAfter 1 hr at room temperature
2. extractionextracted with ethyl acetate
3. dry with materialThe organic solution was dried over magnesium sulfate
4. customThe solvent was removed
5. customthe residue was purified by chromatography on silica gel
6. washProduct eluted with ethyl acetate-methanol-triethylamine 40:8:1 giving 0.87 g of the free base
7. dissolutionThis was dissolved in 20 ml of ethyl acetate
8. addition10 ml of a solution of hydrogen chloride in ether was added
9. customThe solid was collected