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Development of the synthesis of BEZ235 on ton scale

Baenziger, Markus, Pachinger, Werner, Stauffer, Frederic and Zaugg, Werner (2019) Development of the synthesis of BEZ235 on ton scale. Organic Process Research & Development, 23 (9). pp. 1908-1917. ISSN 1083-61601520-586X


ABSTRACT: The development of a robust synthesis of 2-Methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]propionitrile (NVP-BEZ235 (Dactolisib); compound 10) to a ton-scale process is described. The key step is a Pd-catalyzed Suzuki coupling of 2[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]2-methyl-propionitrile to 3-quinoline boronic acid. A special focus is put on the reduction of the amount of Pd catalyst used in the Suzuki coupling and the removal of traces of Pd from the crude drug substance, as well as the purification of the crude drug substance.

Item Type: Article
Date Deposited: 06 Oct 2019 00:45
Last Modified: 06 Oct 2019 00:45