Potassium Carbonate → 5-(1-azetidin-3-yl-1H-pyrazol-4-yl)-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-[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 (100.0 mg, 0.230 mmol), 3-(4-iodopyrazol-1-yl)-azetidine-1-carboxylic acid tert-butyl ester (88.3 mg, 0.253 mmol), Pd(PPh3)4 (10 mg, 0.01 mmol), potassium carbonate (95.3 mg, 0.689 mmol) and 4:1 dioxane/H2O (8 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 water. The organic layer was concentrated in vacuo, redissolved in dioxane, and 4M HCl in dioxane (1 mL) was added. The solution was heated to 45° C. for 3 h. The solvents were removed on the corrosive pump, and the material was dry-loaded onto silica gel for column chromatography, eluting with 3-6% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 1.88 (d, J=7.3 Hz, 3 H), 3.90-3.98 (m, 2 H), 4.08-4.15 (m, 2 H), 5.20-5.34 (m, 2 H), 7.18 (t, J=8.6 Hz, 1 H), 7.36 (d, J=1.3 Hz, 1 H), 7.36-7.48 (m, 2 H), 7.65 (s, 1 H), 7.95 (s, 1 H), 8.32 (d, J=2.0 Hz, 1 H). MS (ES+): m/z 430.10 (100) [MH+]. HPLC: tR=2.25 min (ZQ3, polar—5 min).

Provenance & Evidence