Sodium Carbonate → 4-(4-Fluorophenyl)-7-(pyrimidin-5-ylmethyl)quinoline-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

Degassed DME (1237 μl)/Water (619 μl) was added to 7-(bromomethyl)-4-(4-fluorophenyl)quinoline-2-carboxamide (3-1, 100 mg, 0.278 mmol), pyrimidin-5-ylboronic acid (41.4 mg, 0.334 mmol), Pd(PPh3)4 (16.09 mg, 0.014 mmol), and Na2CO3 (62.0 mg, 0.585 mmol). The reaction was heated at 100° C. in the microwave for 10 minutes. The reaction was quenched with water and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The crude material was purified by flash column chromatography (12 g SiO2, 0-100% EtOAc/hexanes) to afford impure product. The material was purified further by reverse phase HPLC (20×150 mm, Waters Sunfire, Solvent A=0.1% TFA/H2O, Solvent B=0.1% TFA/MeCN, 20 ml/min) to afford, after basic workup, 4-(4-fluorophenyl)-7-(pyrimidin-5-ylmethyl)quinoline-2-carboxamide (6-3, 8.16 mg, 8.18% yield) as a white solid. 1H NMR (500 MHz, CDCl3): δ 9.14 (s, 1H); 8.68 (s, 2H); 8.23 (s, 1H); 8.05 (s, 1H); 7.97 (s, 1H); 7.93 (d, J=8.7 Hz, 1H); 7.50 (dd, J=8.5, 5.4 Hz, 2H); 7.42 (dd, J=8.7, 1.8 Hz, 1H); 7.24 (t, J=8.5 Hz, 2H); 5.64 (s, 1H); 4.22 (s, 2H). LRMS m/z (M+H)+ 359.2 found, 359.4 required.

Provenance & Evidence