反应详情

温度

120 °C

A mixture of 6-methoxycarbonyl-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidine (Example 56) (200 mg, 0.45 mmol) and morpholine (0.5 ml, 5.73 mmol) in anhydrous methanol (5.0 ml) was heated at 120° C. for 18 hours. The volatiles were removed by evaporation and the residue was purified by reverse phase HPLC using a C18 column eluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2). Product containing fractions were combined and passed through a 50 g isolute SCX-2 ion exchange column. The column was eluted with methanol to elute any neutrals, followed by 7M methanolic ammonia to elute the product. The solvent was removed by evaporation and the residue was triturated with diethylether. The resulting solid was collected by filtration to give the title compound (120 mg, 52%).

1. customThe volatiles were removed by evaporation
2. customthe residue was purified by reverse phase HPLC
3. washeluting with water/acetonitrile/TFA (95:5:0.2 decreasing in polarity to 0:100:0.2)
4. additionProduct containing fractions
5. washThe column was eluted with methanol
6. washto elute any neutrals
7. washto elute the product
8. customThe solvent was removed by evaporation
9. customthe residue was triturated with diethylether
10. filtrationThe resulting solid was collected by filtration