反应详情

To a solution of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1,4′-bipiperidin-2-one hydrochloride (prepared according to the method of Example 45) (0.100 g, 0.246 mmol) in 5 mL MeOH was added KOH (0.014 g, 0.246 mmol). The mixture was stirred for 30 minutes at ambient temperature, cooled in an ice bath and filtered through a syringe filter, and the filtrate was concentrated and used directly. To the obtained residue was added 2-chloro-5-ethyl-3-methylpyridine (0.0460 g, 0.296 mmol), toluene (5 mL), Pd(OAc)2 (0.00830 g, 0.0370 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (also known as “DavePhos”) (0.0291 g, 0.0739 mmol), and NaOtBu (0.0710 g, 0.739 mmol) and the mixture was heated at 110° C. overnight. The reaction was cooled to ambient temperature, diluted with water and extracted with CH2Cl2. The organic layers were combined, dried over Na2SO4 and purified on silica gel eluting with 100% EtOAc to give 1′-(5-ethyl-3-methylpyridin-2-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1,4′-bipiperidin-2-one (0.080 g, 66.5% yield) as a white solid. Mass spectrum (apci) m/z=489.3 (M+H).

1. temperaturecooled in an ice bath
2. filtrationfiltered through a syringe
3. filtrationfilter
4. concentrationthe filtrate was concentrated
5. temperaturethe mixture was heated at 110° C. overnight
6. temperatureThe reaction was cooled to ambient temperature
7. extractionextracted with CH2Cl2
8. dry with materialdried over Na2SO4
9. custompurified on silica gel eluting with 100% EtOAc