Fit-for-Purpose Development of the Enabling Route to Crizotinib (PF-02341066)

Autor:	Ian B. Moses, Rick Rodriguez, Peter Robert Rose, Corey L. Stanchina, Cuthbertson Timothy J, Asayuki Kamatani, Pieter D. de Koning, Alison Sandoval, Kyle Kissick, Robert Moore, Leera Rahman, Douglas McAndrew, Armando Urbina, David C. Boyles
Rok vydání:	2011
Předmět:	chemistry.chemical_compound chemistry Crizotinib Suzuki reaction Pinacol Organic Chemistry medicine Halogenation Organic chemistry Mitsunobu reaction Physical and Theoretical Chemistry Highly selective medicine.drug
Zdroj:	Organic Process Research & Development. 15:1018-1026
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op200131n
Popis:	A robust six-step process for the synthesis of crizotinib, a novel c-Met/ALK inhibitor currently in phase III clinical trials, has been developed and used to deliver over 100 kg of API. The process includes a Mitsunobu reaction, a chemoselective reduction of an arylnitro group, and a Suzuki coupling, all of which required optimization to ensure successful scale-up. Conducting the Mitsunobu reaction in toluene and then crystallizing the product from ethanol efficiently purged the reaction byproduct. A chemoselective arylnitro reduction and subsequent bromination reaction afforded the key intermediate 6. A highly selective Suzuki reaction between 6 and pinacol boronate 8, followed by Boc deprotection, completed the synthesis of crizotinib 1.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6fd5a1469f77db90ff994ded3cb5273e https://doi.org/10.1021/op200131n Zobrazit plný text záznamu