Synthesis and Characterization of Quinoline-3-Carboxamide Derivative

Quinoline derivative (1) was prepared according to our previously reported experimental procedure (Scheme 1).^{19 (link)} A mixture of commercial quinoline-3-carboxylic acid and freshly distilled thionyl chloride was warmed into reflux for 3 h, then cooled to room temperature and evaporated under vacuum to dryness to quantitatively obtain the corresponding chloride acids (1). This crude material was used without further purification. A mixture of this acyl chloride (1, 1.0 equiv.) and 4-aminoacetophenone (2, 1.0 equiv.) in toluene (10 mL) was stirred at room temperature for 2 h and then treated with a saturated NaHCO₃ solution. The biphasic solution was vigorously stirred for 30 min, then decanted, and finally separated. The collected aqueous phase was extracted with EtOAc (2 × 10 mL). The combined organic layer was dried over Na₂SO₄ and evaporated. The solid was washed with icy water and crude material was crystallized from ethanol. Yield 90%, white solid; m.p. = 255–257 °C; IR (KBr, cm⁻¹): 3327, 3068, 3001, 1985, 1918, 1844, 1676, 1650, 1597, 1268, 1109, 799; ¹H NMR (400 MHz, DMSO-d₆) δ_H (ppm): 2.55 (s, 3H), 7.71 (t, J = 8.0 Hz, 1H), 7.89 (t, J = 8.0 Hz, 1H), 7.99 (s, 4H), 8.12 (dd, J = 8.0, 12.3 Hz, 2H), 8.99 (s, 1H), 9.37 (s, 1H), 10.90 (bs, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ_C (ppm): 26.4 (CH₃), 119.5 (2 × CH), 126.3 (C), 127.3 (C), 127.5 (CH), 128.8 (CH), 129.2 (CH), 129.3 (2 × CH), 131.5 (CH), 132.2 (C), 136.2 (CH), 143.4 (C), 148.5 (C), 149.0 (CH), 164.5 (C), 196.5 (C).