反应详情

A mixture of 3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (60.0 mg, 0.138 mmol), trans-4-(4-iodo-pyrazol-1-yl)cyclohexanol (52.4 mg, 0.179 mmol), Pd(PPh3)4 (8 mg, 0.007 mmol), potassium carbonate (57.2 mg, 0.414 mmol) and 4:1 dioxane:water (7 mL) was heated to 90° C. for 2 h. The organic solvent was removed in vacuo, and the material was transferred to a separatory funnel, extracting with DCM and sat. NaHCO3 solution. The organic layer was dry-loaded onto silica gel, and column chromatography was used to purify, eluting with 3-4% (7N NH3 in MeOH)/DCM. The resulting solid was triturated with MeOH to give the title compound. 1H NMR (400 MHz, CD3OD): δ=1.47-1.59 (m, 2 H), 1.88 (d, J=6.8 Hz, 3 H), 1.90-2.03 (m, 2H), 2.10-2.22 (m, 4 H), 3.66 (tt, J=10.9, 4.2 Hz, 1 H), 4.17 (tt, J=11.6, 4.0 Hz, 1 H), 5.27 (q, J=7.0 Hz, 1 H), 7.18 (dd, J=8.4, 8.8 Hz, 1 H), 7.38 (d, J=1.3 Hz, 1 H), 7.44 (d, J=2.0 Hz, 1 H), 7.46 (br. s., 1 H), 7.54 (d, J=0.8 Hz, 1 H), 7.87 (d, J=0.8 Hz, 1 H), 8.32 (d, J=2.0 Hz, 1 H). MS (ES+): m/z 473.01/475.04 (100/70) [MH+]. HPLC: tR=3.36 min (ZQ3, polar—5 min). This material was redissolved in DCM. 2.0 M of HCl in Et2O (0.8 mL) was added at rt and stirred for 20 min. The mixture was concentrated in vacuo to afford the title compound as an HCl salt.

1. customThe organic solvent was removed in vacuo
2. customthe material was transferred to a separatory funnel
3. extractionextracting with DCM and sat. NaHCO3 solution
4. customto purify
5. washeluting with 3-4% (7N NH3 in MeOH)/DCM
6. customThe resulting solid was triturated with MeOH