Synthesis of Cinacalcet Hydrochloride: A Case Study on the Impact of Agitation Speed on the Reaction Kinetics of Schiff’s Base during Scale-up

Abstract During the process development of Cinacalcet hydrochloride, a calcimimetic agent, we encountered an unexpected substantial increase in the content of impurities in the product while scaling up the process in the pilot plant. Detailed investigation led to the conclusion that the agitation sp...

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Bibliographic Details
Published in:SynOpen (2017) 2018-01, Vol.2 (1), p.0072-0077
Main Authors: Jagtap, Kunal M., Shinde, Gorakshanath B., Niphade, Navnath C., Teldhune, Ashish P., Toche, Raghunath B., Mathad, Vijayavitthal T.
Format: Article
Language:English
Subjects:
agitation speed
calcimimetic drug
cinacalcet
letter
reaction kinetics
scale-up
schiff’s base
tips speed
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Summary:Abstract During the process development of Cinacalcet hydrochloride, a calcimimetic agent, we encountered an unexpected substantial increase in the content of impurities in the product while scaling up the process in the pilot plant. Detailed investigation led to the conclusion that the agitation speed of the reaction mass impacted the reaction kinetics of Schiff’s base, leading to the formation of the impurities and lowering the product yield to ca. 40%. The present work reports details of an investigation carried out to control the formation of impurities to achieve an efficient and one-pot process for Cinacalcet hydrochloride with an overall yield of ca. 70%.
ISSN:2509-9396
2509-9396
DOI:10.1055/s-0036-1591772