Potassium Carbonate → N-(4-(Chlorodifluoromethoxy)phenyl)-6-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl)-5-(4-methylpyrimidin-5-yl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

N-(4-(chlorodifluoromethoxy)phenyl)-6-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl)-5-iodonicotinamide (Stage 282.1, 100 mg, 0.190 mmol) and 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (Stage 297.1, 62.8 mg, 0.285 mmol), Pd(Ph3P)4 (21.98 mg, 0.019 mmol) and K2CO3 (79 mg, 0.571 mmol) were added to a vial and flushed with argon. DMF (2 mL) was added and the mixture was stirred at 100° C. for 2 h. The solvent was evaporated off under reduced pressure. The crude product was dissolved in MeOH, filtered through a PL-resin Si-Thiol cartridge, the cartridge was washed with MeOH and the solvent was evaporated off under reduced pressure to give a residue which was purified by preparative HPLC (Condition 14-25% to 55% MeCN in 20 min) and followed by preparative SFC (Column Diol, from 20% to 25% in 6 min). The purified product was lyophilized in water/min vol. MeCN to afford the title product as a white powder. UPLC-MS (Condition 3), tR=0.86 min, m/z=492.2/494.2 [M+H]+.

Provenance & Evidence