An integrated flow and microwave approach to a broad spectrum protein kinase inhibitor. Issue 113 (2nd November 2015)

• Record Type: Journal Article
• Authors: Russell, Cecilia; Lin, Andrew J. S.; Hains, Peter; Simone, Michela I.; Robinson, Phillip J.; McCluskey, Adam
• Is Part Of: RSC advances. Volume 5:Issue 113(2015)
• Page Start: 93433
• Page End: 93437
• Publication Date: 2015-11-02
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5ra09426g
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : The protein kinase inhibitor CTx-0152960 and the piperazinyl analogue CTx-0294885 were prepared using a hybrid flow and microwave approach. 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 SN Ar coupling with 1-fluoro-4-nitrobenzene. Microwave coupling of 4-morphilinoaniline8 and 4-(piperazine-1-yl)aniline9 with 2-(2, 5-dichloropyrimidine-4-ylamino)- N -methylbenzamide10, proved to be the most efficacious route to the target analogues6 and7 . 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.