Industrial proparation of Rivastigmine tartarate and synthesis of its Azolic derivatives

Alzheimer disease (AD) is a complex neurological affection that is clinically characterized by loss of memory. Rivastigmine, an acetyl cholinesterase (AChE) inhibitor approved in 2000 for the treatment of AD, bears a carbamate moiety in its structure, which is able to react covalently with the active site of the enzyme [1,2]. Our process for the straight forward synthesis of enantiomerically pure Rivastigmine Tartarate, (S)-N-ethyl-N-methyl-3-[-(dimethylamino)ethyl]-phenyl carbamate hydrogen- (2R,3R)-tartarate withUSP38 has been efficiently carried out under mild reaction condition with NaOMe as a basic catalyst, that is easy to scale up in industry and suitable for the manufacture of Rivastigmine in active pharmaceutical ingredient (API) demand. This process is convenient operation and purification and completes the synthesis of RivastigmineTartarate in 93% overall yield. The purity of product was characterized by HPLC analysis. On the basis of previous studies on a series of benzopyrano[4,3-b]pyrrolecarbamates asacetyl cholinesterase (AChE) inhibitors, we designed and synthesis a series of conformationally analogues of Rivastigmine by including the N-ethyl-N-methyl carbamoyl moiety in different azolic systems.