Diisopropylethylamine → 1-[4-(Cyanomethyl)-1-pyrimidin-4-ylpiperidin-4-yl]-3-[(4-fluorophenyl)amino]-1H-pyrazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-{4-carbamoyl-3-[(4-fluorophenyl)amino]-1H-pyrazol-1-yl}-4-(cyanomethyl)piperidinium trifluoroacetate (Intermediate #38-5) (50 mg, 0.11 mmol) in DCE (1.0 mL) was added DIPEA (0.096 mL, 0.55 mmol) followed by 4-bromopyrimidine (32 mg, 0.16 mmol). The reaction mixture was heated under microwave irradiation to 130° C. and allowed to stir for 15 minutes. The reaction mixture was then cooled to ambient temperature and diluted with a mixture of DCM and IPA. The resulting mixture was sequentially washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting residue 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, Example #26, as a solid.

Provenance & Evidence