Sodium Carbonate → (R)-Methyl 6-(3-hydroxypyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinate

Participants

Reaction Conditions

Reaction Steps

(R)-Methyl 5-bromo-6-(3-hydroxypyrrolidin-1-yl)nicotinate (Stage 170.3, 930 mg, 3.1 mmol) and pyrimidin-5-ylboronic acid (765 mg, 6.2 mmol) were dissolved in a solution of DME (5 mL) and EtOH (0.7 mL). A solution of 2 M Na2CO3 (4.63 mL, 9.26 mmol) was added, the mixture was flushed with argon, Pd(PPh3)2Cl2 (260 mg, 0.371 mmol) was added and the RM was stirred at 95° C. in a pressure safe vial for 1.5 h. After cooling at RT, the RM was treated with brine and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue that was purified by flash chromatography (RediSep® Silica gel column, (DCM/MeOH 98:2)/MeOH, from 0 to 5% MeOH) a treated with Si-Thiol (1 g) in MeOH to afford the title compound as a grey foamy powder. HPLC (Condition 4) tR=2.95 min, UPLC-MS (Condition 7) m/z=301.1 [M+H]+.

Provenance & Evidence