反应详情

To a flask containing a solution of 4-(3-Aminopropyl)-morpholine (117 μl, 0.79 mmol) in pyridine (1 mL) was added 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride (230 mg, 0.72 mmol) dissolved in pyridine (5 mL). The reaction was allowed to stir under a nitrogen atmosphere overnight. The reaction was not complete so an additional equivalent of 4-(3-Aminopropyl)-morpholine (100 μl, 0.72 mmol) was added. The reaction was allowed to stir at room temperature overnight. LCMS showed the product formation. Solvent was removed by rotary evaporation. The reaction was treated with water and the product was extracted with ethyl acetate and dichloromethane. The organic layers were combined and washed with saturated aqueous sodium carbonate solution and brine. The organic layer was dried with magnesium sulfate, filtered and concentrated to yield the product. This was purified by semi-preparative HPLC. The product was washed with a sodium bicarbonate solution to remove the TFA salt to yield the title compound (37.3 mg, 13.5% yield). 1H NMR (DMSO-d6) δ 8.6 (m, 1H), 8.5 (m, 1H), 8.0 (m, 2H), 7.9 (m, 1H), 7.7 (m, 1H), 7.4 (m, 2H), 3.3 (m, 4H), 3.1 (m, 2H), 2.3 (m, 6H), 1.6 (m, 2H) ES-MS m/z 383 [M+1]+.

1. additionwas added
2. stirringto stir at room temperature overnight
3. customSolvent was removed by rotary evaporation
4. additionThe reaction was treated with water
5. extractionthe product was extracted with ethyl acetate and dichloromethane
6. washwashed with saturated aqueous sodium carbonate solution and brine
7. dry with materialThe organic layer was dried with magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto yield the product
11. customThis was purified by semi-preparative HPLC
12. washThe product was washed with a sodium bicarbonate solution
13. customto remove the TFA salt