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 |
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Rok vydání: | 2004 |
Předmět: | |
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 |
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