反应详情

温度

120 °C

A solution of 4-chloro-5,7-dihydro-1H-pyrolo[3′,4′:4,5]thieno[2,3-d]pyrimidine-6-carboxylic acid benzyl ester (prepared in an analogous fashion to 4-chloro-5,8-dihydro-6H-pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester, WO2007/109279, 0.135 g, 0.39 mmol), 4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)aniline (0.090 g, 0.39 mmol) and para-toluene sulfonic acid (0.08 g, 0.04 mmol) in 1,4-dioxane (2 mL) was purged with nitrogen and heated at 120° C. for 21 hours. The reaction mixture was diluted with EtOAc, washed with 10% aqueous K2CO3 and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (100% iso-hexane→100% DCM→3% MeOH/DCM→200:10:1 DCM/MeOH/NH4OH) to afford the title compound as white solid (0.015 g, 10%).

1. customwas purged with nitrogen
2. additionThe reaction mixture was diluted with EtOAc
3. washwashed with 10% aqueous K2CO3 and brine
4. dry with materialThe organic phase was dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash column chromatography (100% iso-hexane→100% DCM→3% MeOH/DCM→200:10:1 DCM/MeOH/NH4OH)