反应详情

1,1-Dimethylethyl (2R)-2-{([(4-{2-[(4-morpholin-4-ylphenyl)amino]pyrimidin-4-yl}-phenyl)amino]carbonyl}pyrrolidine-1-carboxylate (0.38 g, 0.698 mmoles), was dissolved in an ethyl acetate (10 ml) and methanol (2 ml) mixture. 4 M hydrogen chloride in 1,4-dioxane (1.75 ml, 6.98 mmoles, 10 equivalents, purchased from Sigma-Aldrich) was then added in a drop wise fashion over 5-10 minutes. Upon completion of addition, the reaction mixture was stirred at room temperature, and the progress of the reaction monitored by LC/MS. After 16 hours, additional 4M hydrogen chloride in 1,4-dioxane (0.87, 1.25 mmoles, 5 equivalents) was added. After a total of 48 hours the reaction was complete and the resulting slurry was filtered off. The reaction flask was rinsed with ethyl acetate to ensure complete transfer of product. The resulting solid was washed with ethyl acetate (3×10 ml), followed by diethyl ether (3×25 ml) and dried under reduced pressure to give of 0.264 mg 2-methyl-N-(4-{2-[(4-morpholin-4-ylphenyl)amino]-pyrimidin-4-yl}phenyl)prolinamide (68% yield).

1. additionUpon completion of addition
2. customAfter a total of 48 hours
3. filtrationthe resulting slurry was filtered off
4. washThe reaction flask was rinsed with ethyl acetate
5. washThe resulting solid was washed with ethyl acetate (3×10 ml)
6. customdried under reduced pressure