2-Bromopyridine → 1-(4-(Cyanomethyl)-1-(pyridin-2-yl)piperidin-4-yl)-3-(4-fluorophenylamino)-1H-pyrazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (52 mg, 0.11 mmol), copper (I) iodide (2 mg, 0.01 mmol), L-proline (3 mg, 0.02 mmol) and K3PO4 (48 mg, 0.23 mmol) was dissolved in DMSO (0.16 mL). 2-Bromopyridine (0.011 mL, 0.11 mmol) was added, and the resulting mixture was heated to 90° C. and allowed to stir for 72 hours. The reaction mixture was then allowed to cool to ambient temperature and was filtered. The filtrate was purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound as a solid.

Provenance & Evidence