反应详情

To a solution of 4-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-5,7-dihydro pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester in DCM (20 mL), TFA (20 mL, 260 mmol) is added at 0° C. The reaction is allowed to reach room temperature and stirred for an additional 1 h. TFA/DCM are evaporated and then the product is taken up in EtOAc (100 mL) and washed with dilute NH4OH in H2O (20 mL). The organic layer is separated and the water layer is extracted further with EtOAc (2×). The combined organics are dried and evaporated. The crude residue is separated via FCC (eluted with DCM/MeOH/NH4OH (100:0:0 to 93:6:1)) to give 5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl phenyl)-amide. MS (ESI) m/z 440.9 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.55 (s, 1H) 8.33 (d, J=8.84 Hz, 1H) 8.06 (br. S., 1H) 7.89 (d, J=8.34 Hz, 1H) 7.94 (d, J=3.54 Hz, 1H) 7.57 (t, J=7.96 Hz, 1H) 7.41-7.46 (m, 2H) 7.13 (dd, J=9.09, 2.27 Hz, 1H) 6.74 (d, J=3.03 Hz, 1H) 4.26 (d, J=12.13 Hz, 4H).

1. customto reach room temperature
2. customTFA/DCM are evaporated
3. washwashed with dilute NH4OH in H2O (20 mL)
4. customThe organic layer is separated
5. extractionthe water layer is extracted further with EtOAc (2×)
6. customThe combined organics are dried
7. customevaporated
8. customThe crude residue is separated via FCC (eluted with DCM/MeOH/NH4OH (100:0:0 to 93:6:1))