Grignard Reaction Mechanisms | 合法醫療器材資訊網

Grignardreagentsarestrongbasesandwillreactwithproticcompoundswhichmakesthemexceedinglyvaluabletoolsfororganicsynthesis.Asanexample, ...

This research is focused on the development of an optimized route for an aromatic nucleophilic substitution reaction, coupling aminopyridine (3) and chloropyrimidine (7). The product of the reaction is an important intermediate compound in the overall synthesis of the drug Palbociclib.

The research investigated different approaches to coupling the two reagents, and route-dependent mechanisms were postulated. The development of a clinical manufacturing route involved coupling by a strong base, LiHMDS. Though yields were acceptable, the requirement for 2+ equivalents of the aminopyridine intermediate was not ideal. Furthermore, one significant impurity was formed by this reaction, which was found to be a dimer of the product molecule. Coupling with a Grignard base, i-PrMgCl, resulted in good yield without the formation of the dimer.

In situ FTIR measurements provided insight into the kine...