反应详情

A mixture of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 100 mg, 1.0 eq.), 5-bromopyrimidine (44 mg, 1.1 eq.), trans-1,2-diaminocyclohexane (18 mg, 0.65 eq.), copper(I) iodide (6 mg, 0.12 eq.) and potassium phosphate tribasic (110 mg, 2.1 eq.) in dioxan (2.0 mL) was stirred under reflux for 3 d. Potassium carbonate (72 mg, 2.1 eq.) was added and the mixture was refluxed for 1 d, evaporated to dryness and purified on silica gel, eluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide, to yield 121 mg (100%) from the desired product as orange oil. MS (m/e): 484.4 (MH+, 100%).

1. temperatureunder reflux for 3 d
2. temperaturethe mixture was refluxed for 1 d
3. customevaporated to dryness
4. custompurified on silica gel
5. washeluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide