Syntheses of R and S isomers of AF-DX 384, a selective antagonist of muscarinic M2 receptors Original Research Article

Enantiomers of 5,11-dihydro-11-[2-[2-[(N,N-dipropylaminomethyl)piperidin-1-yl]ethylamino]-carbonyl]-6H-pyrido[2,3-b]benzodiazepin-6-one (AF-DX 384) , have been synthesized from (S)-(+) and (R)-(−)-2-[N,N-dipropylaminomethyl]piperidine . The enantiomeric excess of has been determined by capillary electrophoresis by using the α-highly sulphated cyclodextrin (α-HSCD) as chiral selector within the running electrolyte. (S)-(+)-() was prepared from (S)-(−)-pipecolic acid in a 4-step procedure (overall yield: 30%, ee: 99%) and (R)-(−)-AF-DX 384 from (R)-(+)-pipecolic acid. The (R)-(−) isomer exhibited in vitro a 23-fold higher affinity than its enantiomer (S)-(+) towards muscarinic receptors of subtype 2.