反应详情

A mixture of 5-Bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (45.0 mg, 0.116 mmol), 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (71.5 mg, 0.232 mmol), Pd(PPh3)4 (7 mg, 0.006 mmol), potassium carbonate (48.1 mg, 0.348 mmol) and 4:1 Dioxane:water (7 mL) was heated to 90° C. for 2 h. The solution was allowed to cool to rt. 2 M of HCl in water (4 mL) was added until pH 2, and the mixture was stirred at rt overnight. The solution was passed through a SCX cartridge that was washed with MeOH, and the product was eluted with 2M NH3 in MeOH. The material was dry-loaded onto silica gel for column chromatography, eluting with 5% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo, redissolved in DCM, and 2.0 M of HCl in Et2O (0.4 mL) was added. The solution was stirred at rt for 20 min and concentrated in vacuo to afford the title compound as an HCl salt. 1H NMR (400 MHz, CD3OD): δ=1.87 (d, J=7.1 Hz, 3 H), 3.52 (dd, J=5.3, 1.3 Hz, 2 H), 3.95-4.02 (m, 1H), 4.13 (dd, J=14.1, 7.6 Hz, 1 H), 4.31 (dd, J=14.0, 4.2 Hz, 1H), 5.27 (q, J=7.1 Hz, 1 H), 7.17 (dd, J=8.6, 8.6 Hz, 1H), 7.35 (d, J=1.3 Hz, 1 H), 7.37 (d, J=2.0 Hz, 1 H), 7.41 (br. s., 1 H), 7.59 (s, 1 H), 7.82 (s, 1 H), 8.31 (d, J=2.0 Hz, 1 H). MS (ES+): m/z=448.99/451.01 (100/68) [MH+]. HPLC: tR=3.05 min (polar—5 min, ZQ3).

1. washwas washed with MeOH
2. washthe product was eluted with 2M NH3 in MeOH
3. washeluting with 5% (7N NH3 in MeOH)/DCM
4. additionThe fractions containing the pure product
5. concentrationwere concentrated in vacuo
6. dissolutionredissolved in DCM
7. addition2.0 M of HCl in Et2O (0.4 mL) was added
8. stirringThe solution was stirred at rt for 20 min
9. concentrationconcentrated in vacuo