反应详情

To a stirred solution of 7-chloro-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine (100 mg, 0.536 mmol) in DMF (2.0 mL) was added sodium hydride (28.0 mg, 0.643 mmol, 55% dispersion in oil) under a N2 atmosphere. The reaction was stirred at rt for 15 min. After this time 4-chloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (146 mg, 0.536 mmol) in DMF (3.0 mL) was added and the reaction was heated at 60° C. for 1 h and at 100° C. overnight. After this time more NaH (28.0 mg, 0.643 mmol, 55% dispersion in oil) was added and the reaction was heated at 120° C. for 3 h. The reaction was then cooled to rt and partitioned between EtOAc and water. The separated organic layer was washed with LiCl (1.0M aqueous solution) and then it was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography (Hexanes:EtOAc, 1:0 to 1:1) gave 7-chloro-1-(5-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine as a yellow film. Mass Spectrum (ESI) m/e=423.0 (M+1).

1. temperaturethe reaction was heated at 60° C. for 1 h and at 100° C. overnight
2. temperaturethe reaction was heated at 120° C. for 3 h
3. temperatureThe reaction was then cooled to rt
4. custompartitioned between EtOAc and water
5. washThe separated organic layer was washed with LiCl (1.0M aqueous solution)
6. dry with materialit was dried over MgSO4
7. filtrationfiltered
8. customevaporated in vacuo