Reaction of 2‐carboxy‐1‐methylindole‐3‐acetic acid anhydride with amines and with S‐methylisothiosemicarbazide

Abstract

2‐Carboxy‐1‐alkylindole‐3‐acetic acid anhydrides (I) condensed with S‐methylisothiosemicarbazide in DMF to form 5,11‐dihydro‐6‐methyl‐2‐methylthioindolo[3′,2′:4,5]pyrido[1,2‐b]‐s‐triazol‐5‐one (II). Compound II underwent ring opening on refluxing with sodium hydroxide solution to give IV. The anhydride I reacted with primary amines in benzene to give 2‐carboxy‐1‐alkylindole‐3‐acetanilide derivatives (VI) which yielded l‐methylindole‐3‐acetic acid by decarboxylation followed by hydrolysis. Compound II oxidised to the diketo compound X which could be prepared by the hydrolysis of the azomethine derivative IX with acetic acid‐hydrochloric acid mixture. Compound II reacted with benzyl chloride to yield the dibenzyl derivative XII, condensed with p‐chlorobenzaldehyde to form the 11‐p‐chlorobenzylidene derivative XI and coupled with arenediazonium salt to give the 11‐arylhydrazone derivatives XIII.

A model study on installation of (Z)-γ-methylglutaconic acid onto the 3-aminophenol core of divergolide A

“…12 In order to suppress isomerization of the (Z)-double bond during the amidation process, we envisioned to use aminolysis of the anhydride 12 with the aniline derivative 17 in the absence of other basic species (Scheme 3). 15 Thus, alkaline hydrolysis of the N-aryl trifluoroacetamide 15 in refluxing EtOH in the presence of NaOH furnished the aniline 17 in 99% yield. Heating a mixture of 17 with the anhydride 12 in benzene at reflux for 3.5 h regioselectively gave the amide 18 with (Z)-configuration in 96% yield in an isomer pure form.…”

The chemistry of mercapto- and thione- substituted 1,2,4-triazoles and their utility in heterocyclic synthesis

“…Similarly, triazoles 20 and 21 were obtained by the cyclization of the corresponding thiosemicarbazides in alkaline medium 51,52 (Figure 4). …”

“…Also, the triazoles 86 119 , 87 52 , 88 120 and 89 [121][122][123][124] were synthesized by the cyclization of the corresponding thiosemicarbazides in alkaline medium ( Figure 15). …”

Synthesis of pyrano[4,3-b]indoles as conformationally restricted analogs of the serotonin antagonist ICS 205-930 and as precursors to 2-vinylindoles

“…Exposure of 7 to either Eschenmoser's salt in organic solvent or dimethylamine-formaldehyde (pH 3-3.5) in aqueous solution afforded 15 in high yield. Hydrogenation of 15 to 2 (H2 Pd/C), demethylation (HBr), and separation of the resulting diastereomeric mixture by recrystallization completed the synthesis of picenadol (1).…”