反应详情

A mixture of 3-{(1S)-1-[2-chloro-6-(difluoromethoxy)-3-fluorophenyl]ethyl}-5-[5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridine (40.0 mg, 0.0794 mmol), acetic acid (23.8 mg, 0.397 mmol), TBTU (51.0 mg, 0.159 mmol), triethylamine (40.2 mg, 0.397 mmol) and DCM (4 mL, 60 mmol) was stirred at rt for 10 min. The solution was extracted with EtOAc, washed with 1 M HCl, and then sat. NaHCO3. The organic layer was concentrated in vacuo, loaded onto silica gel and purified via column chromatography. The product was eluted with 2-3% (7N NH3 in MeOH)/DCM, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.84 (d, J=7.3 Hz, 3H), 1.93-2.04 (m, 3H), 2.12 (dd, J=15.4, 2.5 Hz, 1H), 2.16 (s, 3H), 2.26 (s, 3H), 2.76-2.88 (m, 1H), 3.32-3.35 (m, 1H), 4.08 (dd, J=14.0, 1.9 Hz, 1H), 4.43-4.54 (m, 1H), 4.64-4.73 (m, 1H), 5.11 (q, J=7.0 Hz, 1H), 6.43 (br. s., 1H), 7.12 (dd, J=8.8, 4.5 Hz, 1H), 7.19 (t, J=8.7 Hz, 1H), 7.38 (d, J=1.8 Hz, 1H), 7.39 (d, J=1.3 Hz, 1H), 7.48 (s, 1H), 8.13 (d, J=2.0 Hz, 1H). MS (ES+): m/z=546.17/548.18 (100/50) [MH+]. HPLC: tR=1.43 min (polar—3 min, UPLC-ACQUITY).

1. extractionThe solution was extracted with EtOAc
2. washwashed with 1 M HCl
3. concentrationThe organic layer was concentrated in vacuo
4. custompurified via column chromatography
5. washThe product was eluted with 2-3% (7N NH3 in MeOH)/DCM
6. additionthe fractions containing the pure product
7. concentrationwere concentrated in vacuo