反应详情

温度

55 °C

To a solution of morpholin-4-yl-[5-(morpholin-2-ylmethoxy)-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-methanone as trifluoroacetate salt (example 1, step 2, 120 mg, 1.0 eq.) in tetrahydrofuran (2 mL) were successively added water (0.004 mL, 1.1 eq.), acetone (0.019 mL, 1.5 eq.), acetic acid (0.040 mL, 3.0 eq.) and a solution of sodium cyanoborohydride in tetrahydrofuran (1M, 0.33 mL, 1.5 eq.). The reaction mixture was stirred at 55° C. overnight and concentrated in vacuo. Water (5 mL) and hydrochloric acid (1N, 1.5 mL) were added to the residue and the solution was washed with ethyl acetate and then basified by addition of an aqueous solution of potassium carbonate. The aqueous fraction was extracted with ethyl acetate and the combined organic layers were washed with brine. The organic residue was purified on silica, eluting with 98:2 dichloromethane/methanol, to yield 45 mg (43%) of the desired product as white foam. MS (m/e): 470.5 (MH+, 100%).

1. concentrationconcentrated in vacuo
2. additionWater (5 mL) and hydrochloric acid (1N, 1.5 mL) were added to the residue
3. washthe solution was washed with ethyl acetate
4. additionbasified by addition of an aqueous solution of potassium carbonate
5. extractionThe aqueous fraction was extracted with ethyl acetate
6. washthe combined organic layers were washed with brine
7. customThe organic residue was purified on silica
8. washeluting with 98:2 dichloromethane/methanol