2-Aminothiazole → 1-[3-Fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-3-(thiazol-2-yl)urea
Reaction equation
[F:1][C:2]1[C:3]([O:11][C:12]2[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[F:20])=[C:4]([CH:8]=[CH:9][CH:10]=1)C(O)=O.[C:21](Cl)(=[O:25])C(Cl)=O.[N-:27]=[N+]=[N-].[Na+].[NH2:31][C:32]1[S:33][CH:34]=[CH:35][N:36]=1>ClCCCl>[F:1][C:2]1[C:3]([O:11][C:12]2[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[F:20])=[C:4]([NH:27][C:21]([NH:31][C:32]2[S:33][CH:34]=[CH:35][N:36]=2)=[O:25])[CH:8]=[CH:9][CH:10]=1Participants
Procedure
Methyl 3-fluoro-2-(2-fluoro-6-methoxyphenoxy)benzoate (0.88 g, 60%) was prepared from methyl 2,3-difluorobenzoate (0.86 g, 5 mmol) and 2-fluoro-6-methoxyphenol (0.78 g, 5.5 mmol) as described in procedure A. Hydrolysis of this ester with LiOH in aqueous methanol furnished 2-(2-methoxy-6-fluorophenoxy)-3-fluorobenzoic acid (0.86 g, 90%). To a solution of 3-fluoro-2-(2-fluoro-6-methoxyphenoxy)benzoic acid (0.56 g, 2.0 mmol) in 1,2-dichloroethane (10 ml) was added oxalyl chloride (0.18 ml, 2.2 mmol). The solution was stirred at room temperature for 45 min. To this solution was added NaN3 (390 mg, 6 mmol) and the mixture was heated to reflux for 3 h. 2-Aminothiazole (200 mg, 2 mmol) was then added to this mixture and was further refluxed for 3 h. The mixture was concentrated and the residue was purified by column chromatography (silica, CH2Cl2 then 10% ethyl acetate in CH2Cl2) to afford 1-[3-fluoro-2-(2-fluoro-6-methoxyphenoxy)phenyl]-3-(thiazol-2-yl)urea in (414 mg, 55%).
Workup
- temperaturethe mixture was heated
- temperatureto reflux for 3 h
- temperaturewas further refluxed for 3 h
- concentrationThe mixture was concentrated
- customthe residue was purified by column chromatography (silica, CH2Cl2
Sources & evidence
- ORD record
- ord-d897253ee32741dd9b6ee58e30ac4f2e
- Source dataset
- uspto-grants-2009_06
- Patent number
- US07541373B2
Reaction notes
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