Reginald O. Cann, Chung-pin Chen, Q. Gao
Nov 26, 2012
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0
Influential Citations
13
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Journal
Organic Process Research & Development
Abstract
(R)-N-(3-(7-Methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl)piperazine-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide (1) is a potent calcitonin gene-related peptide (CGRP) receptor antagonist. We have developed a convergent, stereoselective, and economical synthesis of the hydrochloride salt of 1 and demonstrated the synthesis on a multikilogram scale. Two different routes to the chiral indazolyl amino ester subunit were developed utilizing either a Rh-catalyzed asymmetric hydrogenation or a biocatalytic process to install the single chiral center. The advantages and disadvantages of each of these process routes are discussed, as are challenges addressed in the assembly of the final drug substance.