7-(Benzyloxy)-4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazoline → 4-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

Participants

Reaction Steps

7-(Benzyloxy)-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (40 kg) was dissolved in 1-methyl-2-pyrrolidinone (206 kg) at 40-45° C. This solution was charged to an inerted pressure vessel containing 10% palladium on carbon catalyst (0.235 kg of approximately 50% water wet catalyst). A line wash of 1-methyl-2-pyrrolidinone at 40-45° C. (35 kg) was applied. The mixture was hydrogenated at 45° C. and 3 barg for 3.5 hours. The reactor was purged with nitrogen and recirculated through a Gaf filter before being filtered through a 1 μm Pall filter into a new reactor. A line wash of 1-methyl-2-pyrrolidinone (66 kg) through the filters was applied to give a solution of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-ol. To this solution was added potassium carbonate (10.3 kg) and the mixture heated to 80° C.

Provenance & Evidence