Propargyl alcohol → N-(4-Chlorobenzyl)-2-(hydroxymethyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

Participants

Reaction Steps

To a solution of N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (0.15 g), PdCl2(PPh3)2 (0.0098 g) and CuI (0.0027 g) in diethylamine (5.2 mL) and CH2Cl2 (5 mL) is added propargyl alcohol (0.016 mL). The reaction is stirred at room temperature overnight, then concentrated. The crude residue is partitioned between CH2Cl2 and water. The aqueous layer is extracted with CH2Cl2 (3×). The combined organic layers are dried over Na2SO4 and condensed. The crude product is adsorbed onto silica and chromatographed (Biotage flash 40S, gradient from CH2Cl2 to 2.5% MeOH/CH2Cl2). Product containing fractions are combined and concentrated. The resulting solid is triturated with CH2Cl2/hexanes, filtered and dried to yield 0.029 g (23%) of N-(4-chlorobenzyl)-2-(hydroxymethyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide, m.p. 210-212° C.

Provenance & Evidence