Dimethylformamide → N-[(4-chlorophenyl)methyl]-1-methyl-8-[3-(5-methylimidazol-1-yl)prop-1-ynyl]-6-(morpholinomethyl)-4-oxo-quinoline-3-carboxamide

Participants

Reaction Steps

To a solution of N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(morpholin-4-ylmethyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (300 mg), PdCl2(PPh3)2 (19.1 mg), and CuI (5.2 mg) in Et2NH (6.2 mL) is added 5-methyl-1-prop-2-ynyl-1H-imidazole hydrobromide (120.4 mg). Anhydrous DMF (10 mL) is added to help solubilize the reactants (also requires sonication). The reaction is stirred at room temperature overnight, then condensed. The resulting residue is placed under high vacuum to remove residual DMF. The crude product is dissolved in CH2Cl2 and partitioned between CH2Cl12 and saturated NaHCO3. The layers are separated. The aqueous layer is extracted with CH2Cl2 (2×). The combined organic layers are dried over Na2SO4, filtered, and condensed. The crude product is adsorbed onto silica and chromatographed (eluant 1% MeOH in CH2Cl2 (1L), 2% MeOH in CH2Cl2 (1L), 3% MeOH in CH2Cl2 (1L), 4% MeOH in CH2Cl2 (2L), and 6% MeOH in CH2Cl2(1L)). Product-containing fractions are combined and concentrated to afford a residue. The residue is recrystallized from hot acetonitrile to afford 87.7 mg of the title compound as a tan solid.

Provenance & Evidence