A Convenient Synthesis of 2-Aminomethylpyrroles

Elaboration of Benzoxadiazepine and Benzotriazocine Scaffolds

“…Following this synthetic pathway, expected benzo [d]pyrrolo [1,2-f] [1,3,6]triazocin-one and thione were obtained in good overall yield (28 and 30% respectively, scheme 25). [65,66] In 2002, Fathalla and Pazdera evidenced that N-(2-cyanophenyl)-benzimidoyl chloride is a very interesting precursor to provide access to highly functionalized benzotriazocines (Scheme 26). [67] Thus, the authors proposed the reaction between N-(2-cyanophenyl)-benzimidoyl chloride and benzylthiourea as two-site nucleophilic reagent to provide the Nbenzyl-N-carbamothioylbenzimidamide intermediate that promoted spontaneously closure of the benzotriazocine ring.…”

An Update on the Synthesis of Pyrrolo[1,4]benzodiazepines

“…Within the framework of their scientific interests regarding the synthesis of nitrogen containing tricyclic compounds of potential pharmaceutical value, Korakas and Varvounis [89,90] presented the preparation of PBDs 255 and 256 from 1-arylpyrroles 250a , b (Scheme 46). In the first step, pyrroles 250a , b were subjected to Mannich reaction conditions to afford the respective dimethylamino-methylpyrroles 251a , b which were treated with methyl iodide to produce the corresponding quaternary ammonium salts 252a , b .…”

Furan Ring Opening-Pyrrole Ring Closure: Simple Route to 5-Alkyl-2-(aminomethyl)pyrroles

“…This approach was also used in the synthesis of pyrrolo [1,2-a] [1,4]benzodiazepines 11a-c. A solution of diketone 4b in benzene was refluxed with anilines 9a-c in the presence of catalytic amount of trichloroacetic acid to give the corresponding pyrroles 10a-c. On heating with ethanolic hydrazine hydrate, pyrroles 10a-c were transformed into the corresponding pyrrolo [1,2-a] [1,4] By using a similar procedure, we also prepared the pyrrolo [1,2-a]diazepine 14. The diketone 4b, on heating with b-glycine ethyl ester hydrochloride (12) in the presence of sodium acetate, gave the pyrrole 13, which on treatment with hydrazine hydrate in ethanol and N,N-dimethylformamide gave the required product 14 (Scheme 4). 13 To summarize, we have developed a simple and efficient method for the synthesis of 2-(aminomethyl)pyrroles from readily available furfurylamines.…”

“…2-(Aminomethyl)pyrroles have a broad range of biological activities 1 and have been shown to be potential antiinflammatory, 2 analgesic, 3 antidepressant, 4 antipsychotic, 5 or antitumor agents. 6 2-(Aminomethyl)pyrroles have also been used in the treatment of attention-deficit hyperactive disorder; 7 they have also been used in the preparation of conformationally restricted peptidomimetics 8,9 and anionbinding receptors, 9,10 and for the synthesis of pyrrolodiazepines [11][12][13] and other bioactive molecules containing pyrrole units annulated to other heterocycles. 1i, [13][14][15] The 2-(aminomethyl)pyrrole moiety is present in a variety of natural compounds such as porphobilinogen, an important intermediate in the biosynthesis of porphyrins, corrins, and chlorophylls.…”