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
Reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[C:21]([F:30])=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][C:24]([CH3:29])=[CH:23]4)=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:31][CH3:32])C1C=CC=CC=1>CN1CCCC1=O.[Pd]>[F:30][C:21]1[C:20]([O:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([OH:8])=[C:10]([O:31][CH3:32])[CH:11]=3)[N:16]=[CH:15][N:14]=2)=[CH:28][CH:27]=[C:26]2[C:22]=1[CH:23]=[C:24]([CH3:29])[NH:25]2Participants
Procedure
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.
Workup
- additionThis solution was charged to an inerted pressure vessel
- washA line wash of 1-methyl-2-pyrrolidinone at 40-45° C. (35 kg)
- customwas hydrogenated at 45° C.
- customThe reactor was purged with nitrogen
- filtrationfilter
- filtrationbefore being filtered through a 1 μm Pall
- filtrationfilter into a new reactor
- washA line wash of 1-methyl-2-pyrrolidinone (66 kg) through the filters
Sources & evidence
- ORD record
- ord-eeddf9c8a19d45cd899ee888fef44428
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08754240B2
Reaction notes
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