反应详情

To a suspension of methyl 4-(2-(tetrahydro-2H-pyran-4-yloxy)-6-(trifluoromethyl)-pyridin-3-ylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (0.139 g, 0.29 mmol) in EtOH/THF (5 mL; 3:2) was added aqueous sodium hydroxide (2 M, 0.625 mL, 1.25 mmol) and the reaction mixture stirred at ambient temperature for 24 hours. The mixture was diluted with DCM and 10% aqueous KHSO4 and the mixture separated. The organic phase was washed with brine, dried (MgSO4) and the solvent removed in vacuo. The residue was diluted with DMF (2.0 mL) and cooled in ice-water. Hünig's base (44 L, 0.25 mmol) and HATU (0.105 g, 0.28 mmol) were added and the mixture was stirred at this temperature for 20 minutes when 3-(dimethylamino)-propylamine (0.136 mL, 1.24 mmol) was added. The coolant was removed and the reaction stirred at ambient temperature for 18 hours. The mixture was diluted with EtOAc, washed with water and with brine (×2). The organic phase was dried (MgSO4), filtered and the solvent removed in vacuo. The residue was purified by flash column chromatography (100% iso-hexane→100% DCM→250:10:1 DCM/MeOH/NH4OH) followed by trituration of the major component with diethyl ether to afford the title compound as off-white solid (0.01 g, 8%).

1. customthe mixture separated
2. washThe organic phase was washed with brine
3. dry with materialdried (MgSO4)
4. customthe solvent removed in vacuo
5. additionThe residue was diluted with DMF (2.0 mL)
6. temperaturecooled in ice-water
7. additionwas added
8. customThe coolant was removed
9. stirringthe reaction stirred at ambient temperature for 18 hours
10. additionThe mixture was diluted with EtOAc
11. washwashed with water and with brine (×2)
12. dry with materialThe organic phase was dried (MgSO4)
13. filtrationfiltered
14. customthe solvent removed in vacuo
15. customThe residue was purified by flash column chromatography (100% iso-hexane→100% DCM→250:10:1 DCM/MeOH/NH4OH)