Construction of 3-arylpropylamines using Heck arylations. The total synthesis of cinacalcet hydrochloride, alverine, and tolpropamine

Autor(es)

Prediger, Patricia ^[1] ; da Silva, Allan Ribeiro ^[1] ; Duarte Correia, Carlos Roque ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Quim, BR-13084971 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Tetrahedron; v. 70, n. 20, p. 3333-3341, MAY 20 2014.
• Citações Web of Science: 18

Resumo

New synthetic routes toward the commercial drugs cinacalcet hydrochloride, alverine, and tolpropamine were developed using a Heck-Matsuda arylation as the key-step. Several reaction conditions were evaluated for the Heck-Matsuda reaction using allylamine derivatives and arenediazonium salts. For cinacalcet hydrochloride, N-formylamide provided the best result, furnishing the synthetic target in a very high overall yield (75% over five steps). For alverine, the best results were obtained using a double Heck-Matsuda strategy, providing alverine in an excellent overall yield (69%) from N-acetyl diallylamine in three steps. Tolpropamine was synthesized in a 46% yield over five steps using an efficient reductive Heck-Matsuda arylation between p-bromo-methylcinnamate with 3-chloro tolyldiazonium salt, generating the beta,beta-diaryl propionate that was converted to tolpropamine. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 11/23832-6 - Novos estudos metodológicos e mecanísticos das reações de arilação de Heck empregando sais de arenodiazônio e aplicações sintéticas
• Beneficiário: Carlos Roque Duarte Correia
• Modalidade de apoio: Auxílio à Pesquisa - Regular