反应详情

To a mixture of (4-bromo-2-fluorophenyl)[4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone (322 mg) described in Preparation Example 128, (R)-3-methylisothiazolidine 1,1-dioxide (107 mg) described in Preparation Example 2, potassium carbonate (220 mg), copper(I) iodide (76 mg) and potassium iodide (132 mg) were added toluene (1 mL) and N,N′-dimethylethylenediamine (80 μL), and the mixture was stirred with heating under reflux for 8 hr. The reaction mixture was cooled, water was added, the mixture was extracted with chloroform, and the solvent was evaporated. The obtained residue was purified by column chromatography (ethyl acetate:hexane) to give (R)-[2-fluoro-4-(3-methyl-1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone. The obtained (R)-[2-fluoro-4-(3-methyl-1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone (140 mg) was dissolved in ethyl acetate, 4N hydrogen chloride/ethyl acetate (0.08 mL) was added, and the precipitate was collected by filtration to give the title compound (166 mg).

1. temperaturewith heating
2. temperatureunder reflux for 8 hr
3. temperatureThe reaction mixture was cooled
4. extractionthe mixture was extracted with chloroform
5. customthe solvent was evaporated
6. customThe obtained residue was purified by column chromatography (ethyl acetate:hexane)