Water → 4-(3-Chloro-4 (3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methoxy methyl amide
Reaction equation
CO[C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][N:9]=[C:8]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)=[C:18]([Cl:31])[CH:17]=1)=[O:4].Cl.C[NH:34]OC.[Cl-].[NH4+].O.[O:40]1[CH2:44]CC[CH2:41]1>>[CH3:41][O:40][CH2:44][NH:34][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][N:9]=[C:8]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=2)=[C:18]([Cl:31])[CH:17]=1)=[O:4]Participants
Reactant 5
Product 1
Procedure
In tetrahydrofuran (230 ml) was dissolved 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methyl ester (X-1, 11.6 g), N,O-dimethylhydroxylamine hydrochloride (7.8 g) was added, and 2 mol/L iPrMgCl tetrahydrofuran solution (79.8 ml) was added dropwise over 30 minutes under ice cooling. After completion of addition, the mixture was stirred for 20 minutes under ice cooling and, after completion of the reaction, 200 ml of aqueous saturated ammonium chloride solution was added. After 100 ml of water was added to the mixture, the mixture was extracted with ethyl acetate, and the organic layer was dried over sodium sulfate. The filtrate was concentrated to obtain 4-(3-chloro-4 (3-fluorobenzyloxy)phenylamino)-quinazoline-6-carboxylic acid methoxy methyl amide (XI-1, 12.7 g) as a pale yellow solid.
Workup
- additionwas added
- additionAfter completion of addition
- additionwas added
- extractionthe mixture was extracted with ethyl acetate
- dry with materialthe organic layer was dried over sodium sulfate
- concentrationThe filtrate was concentrated
Sources & evidence
- ORD record
- ord-85876b108190431d9ad6ba5892fc912f
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08202879B2
Reaction notes
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