186790-35-2

Upstream product

• 142-84-7 di-n-propylamine 
• 186790-33-0 Toluene-4-sulfonic acid 1-cyanomethyl-piperidin-2-ylmethyl ester 
• 186790-32-9 (2-Bromomethyl-piperidin-1-yl)-acetonitrile 

Relevant academic research and scientific papers

Syntheses of piperidine and perhydroazepine derivatives, precursors of two selective antagonists of muscarinic M2 receptors: AF-DX 384 and its perhydroazepine isomer

Several routes to the synthesis of the polyamines 2a and 2b required for the preparation of the muscarinic antagonists AF-DX 384 1a and its perhydroazepine isomer 1b respectively have been developed and compared. Piperidine 2a has been obtained in 4 steps in 13-15% overall yield from 2-(chloromethyl)-pyridine 3. The perhydroazepine 2b has been prepared in 4 steps in 49% overall yield from 3-aminolactam 7. Transformations of piperidinemethanol 11 afford exclusively compound 2a (5 steps, 17-20% overall yield), via the N-tosylpiperidine 12, but lead to a 1:1 mixture of isomers 2a and 2b (4 steps, 15-20% overall yield for compounds 2a and 2b) via the N-(cyanomethyl)piperidine 15. Limitations to the ring enlargement of piperidine derivatives as a function of the heterocyclic nitrogen substituent are defined.