Dimethyl Sulfoxide → 8-(6-chlorohexyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxyquinolin-2(1H)-one (Intermediate 3) (19.9 g, 56.5 mmol), cesium carbonate (36.9 g, 113 mmol), and DMSO (190 mL) was heated at 30° C. for 15, minutes, and then 1-bromo-6-chlorohexane (12.4 g, 62.2 mmol) was added. The reaction was heated at 30° C. for 4.5 h, diluted with ethyl acetate (2 L), washed with 1M pH 7 phosphate buffer (2 L), and then washed with water (2L×2). The organic layer was dried, filtered, concentrated, and then purified by silica gel chromatography (100% ethyl acetate) to give 19 g of 8-(6-chlorohexyloxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxyquinolin-2(1H)-one as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 10.01 (s, 1H), 8.87 (s, 1H), 8.79 (s, 2H), 7.90 (d, 1H), 7.06 (d, 1H), 4.80 (s, 1H), 3.98 (t, 2H), 3.92 (s, 3H), 3.65 (t, 2H), 1.77 (m, 4H), 1.43 (m, 4H); MS (ESI): 470.3.

Provenance & Evidence