Hydrogen Peroxide → 3-Amino-6-chloro-4-(trifluoromethyl)-2-quinolinecarboxamide

Participants

Reaction Conditions

Reaction Steps

10-Butyl-8-cyano-10-(trifluoromethyl)-5,10-dihydropyrimido[5,4-b]quinolin-4(3H)-one (9, 264 mg, 0.972 mmol) was dissolved in CH3OH—CH2Cl2 (1:2, 6.5 mL) and treated with tetrabutylammonium hydrogen sulfate (109 mg, 0.321 mmol) and 30% aq. H2O2 (1.98 mL). The reaction was cooled to 0° C. and 5N aq. NaOH solution (5.8 mL) was added. After the addition was complete, the reaction mixture had solidified. Additional CH3OH—CH2Cl2 (6 mL) was added to dissolve the solids. The reaction was allow to warm to rt and stir overnight. The reaction mixture was partitioned between EtOAc (25 mL) and H2O (25 mL), and the aqueous layer was extracted with EtOAc (3×15 mL). The combined organic phases were washed with brine, dried (MgSO4) and concetrated. Chromatography (SiO2, 40 g, 30% EtOAc-hexane) afforded the desired product as a yellow crystalline solid (183 mg, 65%). mp 200° C. Rf 0.37 (10% EtOAc-hexane). 1H NMR (CDCl3, 300 MHz) δ 8.20 (br s, NH2), 7.91 (m, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.40 (dd, J=2.2, 9.0 Hz, 1H), 5.63 (br s, NH2); 19F NMR (CDCl3, 300 MHz) δ −54.42; 13C NMR (CDCl3, 75 MHz) δ 168.75, 141.64, 137.05, 136.90, 135.87, 131.96, 128.07, 126.59, 123.84, 121.45, 121.38; IR (KBr) νmax 3515, 3447, 3268, 3204, 1690, 1674, 1597, 1586, 1438, 1357, 1315, 1303, 1226, 1109, 974, 822, 750 cm−1.

Provenance & Evidence