反应详情

温度

88 °C

A mixture of 6-methoxycarbonyl-4-(5-methyl-1H-pyrazol-3-ylamino)-2-{2-[3-(pyrid-2-yl)isoxazol-5-yl]pyrrolidin-1-yl}pyrimidine (Example 45) (49.5 mg, 0.11 mmol) and ethanolamine (2.0 ml, 33.7 mmol) in methanol (4 ml) was heated at 88° C. for 2 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) the fractions containing product were combined and passed through a 50 g isolute SCX-2 ion exchange column. The column was eluted with methanol to elute any neutral impurities, followed by 7M methanolic ammonia to elute the product. The solvent was removed by evaporation, the residue triturated with diethylether and the resulting solid collected by filtration to give the title compound (27 mg, 57%).

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) the fractions
4. additioncontaining product
5. washThe column was eluted with methanol
6. washto elute any neutral impurities
7. washto elute the product
8. customThe solvent was removed by evaporation
9. customthe residue triturated with diethylether
10. filtrationthe resulting solid collected by filtration