Trifluoroacetic acid → HCID 136351726, compound
Reaction equation
Cl.C([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:22]=3[F:28])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1OC)C1C=CC=CC=1.[C:31](O)(C(F)(F)F)=[O:32]>>[F:28][C:22]1[CH:23]=[C:24]([CH3:27])[CH:25]=[CH:26][C:21]=1[NH:20][C:14]1[C:13]2[C:18](=[CH:19][C:10]([OH:9])=[CH:11][CH:12]=2)[N:17]=[C:16]([O:32][CH3:31])[N:15]=1Participants
Procedure
A solution of 7-benzyloxy-4-(2-fluoro-4-methylanilino)-6-methoxyquinazoline hydrochloride (2 g, 4.7 mmol) in TFA (20 ml) was heated at 80° C. for 5 hours and stirred at ambient temperature overnight. The volatiles were removed under vacuum and the residue was suspended in water (50 ml). Solid sodium hydrogen carbonate was added until the pH was approximately 7. The precipitate was then collected by filtration, washed with water and dried under vacuum. The solid was purified by column chromatography eluting with methanol/methylene chloride (5/95). After removal of the solvent by evaporation, the solid was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(2-fluoro-4-methylanilino)-7-hydroxy-methoxyquinazoline (1.04 g, 74%).
Workup
- customThe volatiles were removed under vacuum
- additionSolid sodium hydrogen carbonate was added until the pH was approximately 7
- filtrationThe precipitate was then collected by filtration
- washwashed with water
- customdried under vacuum
- customThe solid was purified by column chromatography
- washeluting with methanol/methylene chloride (5/95)
- customAfter removal of the solvent
- customby evaporation
- customthe solid was triturated with ether
- filtrationcollected by filtration
- washwashed with ether
- customdried under vacuum
Sources & evidence
- ORD record
- ord-fd1fbdfd30964953bc191574e619d866
- Source dataset
- uspto-grants-2007_02
- Patent number
- US07173038B1
Reaction notes
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