反应详情

To a stirred solution of 72 mg (0.42 mmol) 2-choromethyl-isonicotinic acid in 5 ml THF were added 183 mg (0.48 mmol) HATU and 0.08 ml (0.48 mmol) N-ethyldiisopropylamine and stirring continued at room temperature for 5 h. A solution of 80 mg (0.32 mmol) 4-methoxy-7-morpholin-4-yl-benzooxazol-2-yl-amine in 5 ml dioxane and 1 ml DMF was then added and stirring continued at 40° C. for 48 h. The reaction mixture was then poured into 50 ml water, acidified with 1 M aq. hydrochloric acid, and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (3/97 methanol/dichloromethane, then 10/90 methanol/dichloromethane) followed by trituration in ether afforded 8 mg (6%) 2-chloromethyl-N-(4-methoxy-7-morpholin-4-yl-benzooxazol-2-yl)-isonicotinamide as an off-white crystalline solid. ES-MS m/e (%): 405 (M{37Cl}+H+, 35), 403 (M{35Cl}+H+, 100).

1. stirringstirring
2. waitcontinued at 40° C. for 48 h
3. extractionextracted three times with ethyl acetate
4. dry with materialThe combined organic phases were dried over sodium sulfate
5. concentrationconcentrated in vacuo