Thionyl Chloride → 1H-indole-2-carbonyl Chloride

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Reaction Steps

In step 1 of Scheme A, bromobenzaldehyde compound a is reacted with azido ester b under basic conditions to yield indole 2-carboxylate ester c. Compound c is then treated in step 2 with benzyl compound d in the presence of alkali metal hydride to afford 1-benzyl indole compound e. In step 3 a Buchwald reaction is carried out by reaction of compound e with protected piperazine f (other cyclic amine may be used) in the presence of suitable catalyst to provide piperazinyl indole g. The ester portion of compound g is hydrolized under basic conditions in step 4 to afford indole-2-carboxylate compound h. In step 5, indole-2-carboxylate compound h is reacted with a chlorine agent such as thionyl chloride, phosphorus oxychloride of oxalyl chloride, to afford indole-2-carboxylic acid chloride compound i. In step 6 acid chloride compound i is reacted with amine i to afford indole-2-carboxamide compound k. Compound k is then deprotected in step 7 to afford compound m, which is a compound of formula I in accordance with the invention.

Provenance & Evidence