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Synthesis of pyridazino[4,5‐ b ]indole derivatives from 2‐(3‐carboxy‐1‐methylindole)acetic acid anhydride
Author(s) -
Monge A.,
Palop J. A.,
Goñi T.,
FernándezAlvarez E.
Publication year - 1986
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570230128
Subject(s) - chemistry , acetic anhydride , morpholine , piperidine , aniline , hydrate , substituent , hydrazine (antidepressant) , acetic acid , aryl , sodium ethoxide , organic chemistry , medicinal chemistry , sodium hydroxide , ethanol , alkyl , catalysis , chromatography
2‐(3‐Carboxy‐1‐methylindole)acetic acid anhydride ( 1 ) reacts with aryldiazonium salts to give 85–95% of the corresponding α‐hydrazono anhydrides 2 . Treating 2 with boiling hydrazine hydrate in xylene, the respective 2‐aryl‐4‐carbohydrazido‐5‐methyl‐1‐oxo‐1,2‐dihydro‐5 H /‐pyridazino[4,5‐ b ]indoles 3 were obtained (47–67%), and these compounds characterized as the respective benzylidene derivatives 4 . Compounds 2 react with amines (aniline, morpholine, piperidine) to give the respective 2‐(3‐carboxy‐1‐methylindole)aceta‐mide 5 or the respective 2‐aryl‐4‐carboxamido‐5‐methyl‐5 H ‐pyridazino[4,5‐ b ]indole 6 , the product obtained depending on the structure of the aryl substituent. Boiling 2b (aryl = 4‐chlorophenyl) with 5% sodium hydroxide gave (80%) 2‐(3‐carboxy‐1‐methylindole)acetic acid ( 7 ). Hydrolysis of 2b gave a mixture of 7 and 2‐(3‐carboxy‐1‐methylindolyl)‐2‐(4‐chlorophenylhydrazono)acetic acid ( 8 ).