Potassium Phosphate, Tribasic → tert-Butyl 4-(4-carbamoyl-3-(pyrimidin-4-ylamino)-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

K3PO4 (75 mg, 0.35 mmol), X-Phos (21 mg, 0.043 mmol), 4-bromopyrimidine (34 mg, 0.22 mmol) and tert-butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (Intermediate 35-1) (50 mg, 0.14 mmol) were suspended in t-BuOH (3 mL) and degassed with argon for 5 minutes in a microwave vial. The catalyst, Pd2(dba)3 (20 mg, 0.022 mmol), was added and then the mixture was heated at 80° C. for 2 hours. The mixture was then cooled to ambient temperature, Si-DMT (0.10 g) was added and the resulting mixture was allowed to stir for 1 hour. The mixture was filtered and passed through a C18 silica plug. The column was washed with acetonitrile (4 mL) and then the column eluent was evaporated to dryness in vacuo. The crude material was purified by reverse-phase preparative HPLC (MeCN/water, with 0.1% v/v TFA modifier). Desired fractions were identified, combined, passed through a 6 mL Silicycle Carbonate cartridge, and lyophilized to afford the title compound, Example #13-1, as a white solid.

Provenance & Evidence