OTAVA-BB BB7018670077 synthesis

Yield:-

Reaction Conditions:

Stage #1: ethyl 6-iodo-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylatewith sodium hydroxide;water in ethanol; for 1 h;Heating / reflux;
Stage #2: with hydrogenchloride in ethanol;water; pH=2;

Steps:

3

Ethyl 6-iodo-8-methyl-4-oxo-1 ,4-dihydro-3-quinolinecarboxylate (155g) (Intermediate 2) was suspended in a mixture of ethanol (445ml) and 2M sodium hydroxide (870ml), and the mixture was heated under reflux for 1 h. The solution was cooled, the solvent reduced to low volume (400ml removed), and the pH was adjusted to ca. pH 2 with concentrated hydrochloric acid {ca. 150ml) with cooling. A solid separated, which was washed with water, and dried at 40° under vacuum to give the title compound as a white solid (139g). 1 H NMR (400 MHz, DMSO-Cf₆) δ ppm 2.55 (s, 3 H) 8.08 (s, 1 H) 8.40 (s, 1 H) 8.62 (s, 1 H) 12.77 (s, 1 H) 15.02 (s, 1 H).

References:

WO2007/107499,2007,A1 Location in patent:Page/Page column 22