Patent ID: 7282583
Filing Date: 2007-10-16
Classification: C07D

Abstract:
1. A process for making 5,11-dihydro-11-ethyl-5-methyl-8-{2-{(1-oxido-4-quinolinyl)oxy}ethyl}-6H-di pyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one, which process comprises the following steps: (a) reacting 2,3-dihydrofuran with a trialkylorthoformate of the formula  wherein each of the groups R is selected independently and is an alkyl of 1 to 6 carbon atoms, phenyl or cycloalkyl group of 3 to 6 carbon atoms, in the presence of a catalytic amount of an acid, to yield an intermediate of the formula  wherein R is as hereinbefore defined; (b) reacting the intermediate of the formula II, formed in the preceding step, with an acid anhydride of the formula  wherein each R  wherein R  wherein the groups R, R (c) dissolving the substituted penta-2,4-dienenitrile intermediate of the formula V, obtained from the prior step, in a suitable carboxylic acid, and treating it with an anhydrous acid of the formula HX, wherein X is a halogen atom, to yield a substituted pyridine of the formula  wherein R (d) treating the substituted pyridine of the formula VI, obtained from the previous step, with an alcohol of the formula R  wherein R (e) reacting the substituted pyridine of the formula VII, obtained from the preceding step, with ethylamine, in the presence of a catalyst, to yield an aminated intermediate of the formula  wherein R (f) reacting the intermediate of the formula VIII, obtained from the previous step, with 4-hydroxyquinoline, in the presence of a reagent which generates a suitable leaving group from the alcoholic moiety of the compound of the formula VIII, to yield an intermediate of the formula  wherein R (g) hydrolyzing the ester intermediate of the formula IX, obtained from the previous step, to yield the carboxylic intermediate of the formula (h) reacting the carboxylic acid intermediate of the formula X, obtained from the previous step, with an activating agent, to yield an activated acid of the formula XI  wherein Y is OR (i) reacting the activated acid of the formula XI, obtained from the previous step, with 2-chloro-3-methylaminopyridine, to yield a further intermediate of the formula (j) treating the intermediate of the formula XII, obtained from the previous step, with base, to induce ring closure and yield the intermediate of the formula (k) treating the intermediate of the formula XIII with an oxidizing agent to yield the final product, 5,11-dihydro-11-ethyl-5-methyl-8-{2-{(1-oxido-4-quinolinyl)oxy}ethyl}-6H-di pyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one.