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

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• 作者：Patrí ; cia Prediger ; Allan Ribeiro da Silva ; Carlos Roque Duarte Correia ; ^{roque@iqm.unicamp.br" class="auth_mail}
• 关键词：Heck reaction ; Arenediazonium salts ; Cinacalcet hydrochloride ; Alverine ; Tolpropamine
• 刊名：Tetrahedron
• 出版年：20 May, 2014
• 年：2014
• 卷：70
• 期：20
• 页码：3333-3341
• 全文大小：984 K

文摘

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, m>Nm>-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 m>Nm>-acetyl diallylamine in three steps. Tolpropamine was synthesized in a 46% yield over five steps using an efficient reductive Heck-Matsuda arylation between m>pm>-bromo-methylcinnamate with 3-chloro tolyldiazonium salt, generating the 尾,尾-diaryl propionate that was converted to tolpropamine.