反应详情

To a stirred mixture of compound (I) (1.02 g, 2.9 mmol) and 5-amino-2,3-dimethylindole (488 mg, 3.04 mmol) in toluene (6.9 mL) that was heated briefly until components partly dissolved and cooled to ambient temperature, was added 2 M solution of trimethylaluminum in toluene (2.32 mL, 1.6 eq) drop-wise under nitrogen purge. Reaction mixture was stirred until bubbling (gas evolution) completed, and then heated at 115° C. (oil bath) for 15 minutes. To a cooled reaction mixture chloroform and 1 N NaOH were added, chloroform layer was separated, washed twice with water, brine and dried over anhydrous sodium sulfate. Flash column chromatography on silica gel (eluent dichloromethane-acetone-methanol (3:1:01)) and recrystallization from chloroform-ethyl acetate mixture afforded target amide, 2-Morpholin-4-yl-6-(2-morpholin-4-yl-ethoxy)-pyrimidine-4-carboxylic acid (2,3-dimethyl-1H-indol-5-yl)-amide, as a pale yellow solid (1.1 g, 79%).

1. temperaturewas heated briefly until components
2. dissolutionpartly dissolved
3. custompurge
4. customReaction mixture
5. customuntil bubbling (gas evolution)
6. temperatureheated at 115° C. (oil bath) for 15 minutes
7. customTo a cooled reaction mixture chloroform and 1 N NaOH
8. additionwere added
9. customchloroform layer was separated
10. washwashed twice with water, brine
11. dry with materialdried over anhydrous sodium sulfate
12. customFlash column chromatography on silica gel (eluent dichloromethane-acetone-methanol (3:1:01)) and recrystallization from chloroform-ethyl acetate mixture