反应详情

A mixture of 5-bromo-3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (100.0 mg, 0.2606 mmol), 1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (175 mg, 0.521 mmol), Pd(PPh3)4 (15.1 mg, 0.0130 mmol), K2CO3 (108 mg, 0.782 mmol) and 4:1 dioxane:H2O (10 mL, 100 mmol) was heated to 95° C. for 5 h. After cooling to rt, 2 M of HCl in H2O (1.3 mL, 2.6 mmol) was added, and the mixture was heated to 40° C. for 2 h. The organic solvent was removed in vacuo, and the material was extracted with DCM and sat. NaHCO3. The organic layer was purified via column chromatography, eluting with 3-5% MeOH/DCM. The fractions containing the pure product were concentrated in vacuo, redissolved in MeOH, and 2.0 M of HCl in Et2O (1 mL, 2 mmol) was added at rt. The solution was stirred for 30 min, and concentrated in vacuo to afford the title compound as an HCl salt. 1H NMR (400 MHz, CD3OD): δ=1.79 (d, J=7.1 Hz, 3H), 2.00-2.07 (m, 3H), 2.17 (s, 3H), 3.51-3.59 (m, 2H), 3.63 (br. s., 3H), 3.98-4.09 (m, 2H), 4.12-4.19 (m, 1H), 5.09 (q, J=6.8 Hz, 1H), 6.88 (dd, J=9.1, 4.3 Hz, 1H), 7.07 (t, J=8.8 Hz, 1H), 7.30 (s, 1H), 7.35 (d, J=1.3 Hz, 1H), 7.97 (d, J=1.8 Hz, 1H). MS (ES+): m/z=473.07/475.06 (100/50) [MH+]. HPLC: tR=3.13 min (polar—5 min, ZQ3).

1. temperaturethe mixture was heated to 40° C. for 2 h
2. customThe organic solvent was removed in vacuo
3. extractionthe material was extracted with DCM and sat. NaHCO3
4. customThe organic layer was purified via column chromatography
5. washeluting with 3-5% MeOH/DCM
6. additionThe fractions containing the pure product
7. concentrationwere concentrated in vacuo
8. dissolutionredissolved in MeOH
9. concentrationconcentrated in vacuo