The Syntheses Of Chiral Naphthylethylamines And Calcimimetic Cinacalcet

D-tartaric acid could resolve racemic 1-(1-naphthyl)ethylamine into (R)-1-(1-naphthylamne in 39% yield and with 99% e.e., while L-tartaric acid could resolve racemic 1-(1-naphthyl)ethylamine into (S)-1-(1-naphthyl)ethylamine in 38.8% yield and with 98% e.e.. D-tartaric acid could resolve racemic 1-(2-naphthyl)ethylamine into (R)-1-(2-naphthyl)ethylamine in 27.2% yield and with 99% e.e., while D-mandelic acid could resolve racemic 1-(2-naphthyl)ethylamine into (S)-1-(2-naphthyl)ethylamine in 25.4% yield and with 97.6% e.e.. The filtrates containing another enantiomers were subject to recycling resolution, achieving atomic economy and raising yields.The calcimimetic agent cinacalcet(brand name:Sensipar) was approved in the USA in 2004 to treat patients with secondary parathyroidism receiving dialysis for chronic kidney disease. We have compared reported synthetic methods and designed a new one, which started with 3-trifluoromethylbenzaldehyde. After reduction of aldehyde, tosylate formation and nucleophilic substitution with dimethyl malonate, key intermediate 80a is obtained, which underwent subsequent decarboxylation, hydrolysis and carboxylation of amine to yield another key intermediate amide 58. cinacalcet was obtained by reduction of 58 with NaBH4-BF3·OEt2.The total yield of eight steps synthesis is 8.6%.