반응 #418315

반응 방정식

formic acid

pyrimidine-5-boronic acid

(R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine

pyrimidine-5-boronic acid

cesium carbonate

→

(R)-6,6-difluoro-5-(2-fluoro-5-pyrimidin-5-yl-phenyl)-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine

(R)-6,6-Difluoro-5-(2-fluoro-5-pyrimidin-5-yl-phenyl)-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine formate

용매

water

dimethoxyethane

water

반응 조건

후처리

1. 1
   기타The tube was sealed
2. 2
   workup.ADDITIONwere added
3. 3
   온도For the workup, the reaction mixture was cooled to room temperature
4. 4
   여과was filtrated
5. 5
   기타the filtrate purified by preparative HPLC

실험 절차

A degassed solution of (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (20 mg, 59.3 μmol (intermediate A7.1), pyrimidine-5-boronic acid (8.8 mg, 71.2 μmol), and cesium carbonate (77.3 mg, 237 μmol) in a mixture of dimethoxyethane (1 ml) and water (0.5 ml) was treated in a tube under an argon atmosphere with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (CAS 72287-26-4) (2.2 mg, 3.0 μmol). The tube was sealed and heated to 80° C. for 70 minutes. In order to complete the reaction, pyrimidine-5-boronic acid (2.2 mg, 17.8 μmol) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (2.2 mg, 3.0 μmol) were added and stirring continued at 80° C. for 10 minutes. For the workup, the reaction mixture was cooled to room temperature and diluted with water (1.5 ml). After addition of formic acid (0.5 ml) the mixture was filtrated and the filtrate purified by preparative HPLC. The (R)-6,6-difluoro-5-(2-fluoro-5-pyrimidin-5-yl-phenyl)-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine was obtained as a light brown amorphous material (n off-white solid (14 mg, 59% yield). MS (ISP): m/z=337.2 [M+H]+.

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