Modification of Boc-Protected CAN508 via Acylation and Suzuki-Miyaura Coupling

Abstract

The cyclin-dependent kinase inhibitor, CAN508, was protected with di-tert-butyl dicarbonate to access the amino-benzoylated pyrazoles. The bromo derivatives were further arylated by Suzuki-Miyaura coupling using the XPhos Pd G2 pre-catalyst. The coupling reaction provided generally the para-substituted benzoylpyrazoles in the higher yields than the meta-substituted ones. The Boc groups were only utilized as directing functionalities for the benzoylation step and were hydrolyzed under conditions of Suzuki-Miyaura coupling, which allowed for elimination of the additional deprotection step.

Green approach toward protection of secondary amine in pyrazole nucleus by PEG-400 and Boc catalyst

“…PEG-400 has been found to be an adequate and eco-friendly reaction medium for the chemoselective transformation of amines to N-(tert-butoxycarbonyl) amines. Correlated to the previously reported methods, these both protocols (method A and B) offer several advantages such as mild reaction circumstances, easy operation, small reaction period, and high yield (Agami and Couty, 2003;Kelly and Mcneil, 1994;Pisár et al, 2018;Raju et al, 2009;Sharma et al, 2004;Varela et al, 2006). Some various procedures apply for the protection of secondary amine in pyrazole but only two methods (A and B) was succeeded and the other three (C, D, and E) were failed (Fig.…”