反应详情

To a mixture of ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate and 2,2,2-trifluoroethane-1,1-diol in CH2Cl2 (242 μL) at 0° C. was added sodium cyanoborohydride (32.0 mg, 0.509 mmol). The reaction mixture was allowed to stir for 16 hours and then neutralized with 2M aqueous sodium carbonate and extracted with ethyl acetate (×3). The combined organic fractions were dried with sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. The combined fractions containing the desired product were concentrated until only the water layer remained. The water layer was neutralized with saturated aqueous sodium bicarbonate and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried over sodium sulfate, filtered and concentrated under reduced pressure to give ethyl 4-{3-[(2,2,2-trifluoroethyl)amino]phenyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C17H16F3N4O2 [M+H]+: 365, found 365. 1H NMR (600 MHz, DMSO-D6) δ 12.92 (s, 1H), 8.87 (s, 1H), 8.25 (s, 1H), 7.21 (t, 1H, J=7.63 Hz), 7.00 (s, 1H), 6.86 (m, 2H), 6.37 (m, 1H), 3.94 (m, 2H), 3.83 (q, 2H, J=7.04 Hz), 0.81 (t, 3H, J=7.04 Hz).

1. extractionextracted with ethyl acetate (×3)
2. dry with materialThe combined organic fractions were dried with sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by reverse phase HPLC
6. additionThe combined fractions containing the desired product
7. concentrationwere concentrated until only the water layer
8. extractionthe mixture was extracted with ethyl acetate (×3)
9. dry with materialThe combined organic fractions were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure