ABEMACICLIB, BEMACICLIB

Scheme: amide compound S-2 under the action of POCl3 to form chlorine imine intermediate aniline  compound S-1 to accept the attack to give compound S-3, S-3 under basic conditions, pulling  protons, after nucleophilic aromatic substitution reaction  benzimidazole compound S-4, followed by S-4 aryl bromide and B2Pin2 by Pd-catalyzed  reaction, the aromatic substrate was prepared by alcohol  grease S-5, and chlorinated pyrimidine compounds followed through palladium catalyzed  Suzuki reaction S-7 to give the coupling product stand. Secondary amine compound S-8 and S-9 aldehyde through condensation, reduction to  give an amine compound S-10, S-10 and then in the Pd-catalyzed, biphenyl type CyJohnPhos (structure see below) as well as large steric  hindrance ligand As the nitrogen source LiHMDS Preparation of 2-aminopyridine compound S-11. Obtained after S-11, S-7 and its by Buchwald-Hartwig reaction, to give compound S-12,  S-12 compound and formed methanesulfonate obtained Abemaciclib (Bemaciclib)  Reference line: US20100160340 breast cancer drug to Pfizer, Novartis and Eli Lilly's  new drug represented the three companies Palbociclib, Ribociclib and Abemaciclib.  About Palbociclib, Ribociclib synthesis have already posted.

Scheme: amide compound S-2 under the action of POCl3 to form chlorine imine intermediate aniline compound S-1 to accept the attack to give compound S-3, S-3 under basic conditions, pulling protons, after nucleophilic aromatic substitution reaction benzimidazole compound S-4, followed by S-4 aryl bromide and B2Pin2 by Pd-catalyzed reaction, the aromatic substrate was prepared by alcohol grease S-5, and chlorinated pyrimidine compounds followed through  palladium catalyzed Suzuki reaction S-7 to give the coupling product stand. Secondary amine compound S-8 and S-9 aldehyde through condensation, reduction to  give an amine compound S-10, S-10 and then in the Pd-catalyzed, biphenyl type CyJohnPhos (structure see below) as well as large steric hindrance ligand As the  nitrogen source LiHMDS Preparation of 2-aminopyridine compound S-11. Obtained after S-11, S-7 and its by Buchwald-Hartwig reaction, to give compound S-12,  S-12 compound and formed methanesulfonate obtained Abemaciclib (Bemaciclib) Reference line: US20100160340 breast cancer drug to Pfizer, Novartis and  Eli Lilly's new drug represented the three companies Palbociclib, Ribociclib and Abemaciclib. About Palbociclib, Ribociclib synthesis have already posted.

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