反应详情

温度

120 °C

A solution of 4-chloro-5,8-dihydro-6H-pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester (prepared according to WO2007/109279, 0.141 g, 0.43 mmol), 4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)aniline (0.092 g, 0.44 mmol) and para-toluene sulfonic acid (0.08 g, 0.04 mmol) in 1,4-dioxane (2 mL) was purged with nitrogen and then heated at 120° C. for 5 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→66% iso-hexane/EtOAc→100% EtOAc) followed by trituration with MeOH afforded the title compound as white solid (0.042 g, 20%).

1. washwashed with 10% aqueous K2CO3 and brine
2. dry with materialThe organic phase was dried (MgSO4)
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue was purified by flash column chromatography (100% iso-hexane→66% iso-hexane/EtOAc→100% EtOAc)