A Facile and Scaleable Synthesis of ABT-239, A Benzofuranoid H3 Antagonist

Autor:	Ashok K. Gupta, Yu-Ming Pu, Ashok V. Bhatia, Daniel J. Plata, Marlon Cowart, Timothy A. Grieme, Yi-Yin Ku
Rok vydání:	2004
Předmět:	chemistry.chemical_compound Iodophenol Chemistry Yield (chemistry) Organic Chemistry Antagonist Phenol One-Step Physical and Theoretical Chemistry Benzofuran Histamine H3 receptor Combinatorial chemistry Coupling reaction
Zdroj:	Organic Process Research & Development. 9:45-50
ISSN:	1520-586X 1083-6160
Popis:	A facile and scaleable synthesis of a potent and selective histamine H3 receptor antagonist, ABT-239 (1), was developed starting from commercially available 4‘-hydroxy-biphenyl-4-carbonitrile (2). The synthesis comprised four chemical steps and a salt formation step with an overall yield of 40%. A highly selective monoiodination of a phenol was developed and used to prepare iodophenol (3b) in near quantitative yield using NIS in AcOH in the presence of a small amount of H2SO4. A Pd-catalyzed cross coupling reaction of the iodophenols (3b) with butyn-3-ol (4a) provided benzofuran (5) in one step in >80% yield, en route to 1. The new process required no chromatographic purification throughout the synthesis and was successfully demonstrated on scale-up to prepare 1.7 kg of the target ABT-239 (1).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::76aa12a7e085dfbfe212406cb0b4cf4f https://doi.org/10.1021/op049809c Zobrazit plný text záznamu