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Issue 113, 2015
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An integrated flow and microwave approach to a broad spectrum protein kinase inhibitor

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Abstract

The protein kinase inhibitor CTx-0152960 (6, 2-((5-chloro-2-((4-morpholinophenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide), and the piperazinyl analogue, CTx-0294885 (7, 2-((5-chloro-2-((4-piperazin-1-ylphenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide), were prepared using a hybrid flow and microwave approach. The use of flow chemistry approaches avoided the need for Boc-protection of piperidine in the key SNAr coupling with 1-fluoro-4-nitrobenzene. Microwave coupling of 4-morphilinoaniline 8 and 4-(piperazine-1-yl)aniline 9 with 2-(2,5-dichloropyrimidine-4-ylamino)-N-methylbenzamide 10, proved to be the most efficacious route to the target analogues 6 and 7. This hybrid methodology reduced the number of synthetic steps, gave enhanced overall yields and increased atom economy through step reduction and minimal requirement for chromatographic purification, relative to the original batch synthesis approach.

Graphical abstract: An integrated flow and microwave approach to a broad spectrum protein kinase inhibitor

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Supplementary files

Article information


Submitted
20 May 2015
Accepted
05 Oct 2015
First published
05 Oct 2015

RSC Adv., 2015,5, 93433-93437
Article type
Paper
Author version available

An integrated flow and microwave approach to a broad spectrum protein kinase inhibitor

C. Russell, A. J. S. Lin, P. Hains, M. I. Simone, P. J. Robinson and A. McCluskey, RSC Adv., 2015, 5, 93433
DOI: 10.1039/C5RA09426G

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