Triethylamine → N-(4-Chlorobenzyl)-2-[(1R)-1-hydroxyethyl]-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

Participants

Reaction Steps

To a suspension of N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (300 mg), PdCl2(PPh3)2 (39.2 mg), CuI (12.8 mg), and Et3N (0.16 mL) in CHCl3 (5.6 mL) is added (R)-(+)-3-butyn-2-ol (0.053 mL). The reaction is stirred at room temperature for 2 days. The reaction is condensed to remove CHCl3. The solvent is replaced with EtOH (5.6 mL) and additional Et3N (0.16 mL) is added to the reaction mixture. N2 is passed over the surface and the reaction is heated at 60° C. overnight, then allowed to cool to room temperature. The reaction mixture is condensed, adsorbed onto silica, and chromatographed eluting with 1% MeOH in CH2Cl2 to 3% MeOH in CH2Cl2. Product-containing fractions are combined, condensed, and recrystallized from hot acetonitrile to afford 33.8 mg (13%) of N-(4-chlorobenzyl)-2-[(IR)-1-hydroxyethyl]-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide as a tan solid. m.p. 155-159° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.16, 9.42, 8.05, 8.01, 7.40, 7.02, 5.90, 5.26, 4.59, 3.71, 3.58, 2.40, 1.61; IR (diffuse reflectance) 1662, 1629, 1592, 1569, 1541, 1490, 1349, 1294, 1279, 1271, 1245, 1229, 1114, 879, 807 cm−1;

Provenance & Evidence