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 (200.0 mg, 0.5213 mmol), 1-(cis-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (328.8 mg, 0.7820 mmol), Pd(PPh3)4 (30.12 mg, 0.02606 mmol), K2CO3 (216.1 mg, 1.564 mmol) and 4:1 dioxane:H2O (10 mL, 100 mmol) was heated to 95° C. for 2 h. The solution was cooled to rt, and 12 M of HCl in H2O (0.4344 mL, 5.213 mmol) was added. The material was concentrated in vacuo, and extracted with DCM and sat. NaHCO3. The organic layer was dry-loaded onto silica gel and purified via column chromatography, eluting with 2-4% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a light yellow solid. 1H NMR (400 MHz, CD3OD): δ=1.69-1.80 (m, 4H), 1.82 (d, J=7.3 Hz, 3H), 1.94-2.05 (m, 2H), 2.25 (s, 3H), 2.32-2.46 (m, 2H), 3.67 (br. s., 3H), 4.02-4.08 (m, 1H), 4.17-4.27 (m, 1H), 5.08-5.17 (m, 1H), 6.91 (dd, J=9.1, 4.3 Hz, 1H), 7.10 (t, J=8.8 Hz, 1H), 7.36 (d, J=1.3 Hz, 1H), 7.38-7.45 (m, 1H), 7.47 (s, 1H), 8.12 (d, J=2.0 Hz, 1H). MS (ES+): m/z=483.16/485.18 (100/50) [MH+]. HPLC: tR=1.46 min (polar—3 min, UPLC-ACQUITY).

1. concentrationThe material was concentrated in vacuo
2. extractionextracted with DCM and sat. NaHCO3
3. custompurified via column chromatography
4. washeluting with 2-4% (7N NH3 in MeOH)/DCM
5. additionThe fractions containing the pure product
6. concentrationwere concentrated in vacuo