Cinacalcet Hydrochloride → 1-(1-Naphthyl)ethylamine

Participants

Reaction Steps

The invention therefore relates to a process for the preparation of cinacalcet hydrochloride (I) which includes the steps of: a) reacting (R)-(+)-1-(1-naphthyl)ethylamine (II) with 3-[3-(trifluoromethyl)phenyl]propenaldehyde (III) to afford the non isolated intermediate (R)—N-[3-[3-(trifluoromethyl)phenyl]-2-propenylimino-N-[1-(1-naphthyl)ethylamine (IV); b) reducing the non isolated intermediate (R)—N-[3-[3-(trifluoromethyl)phenyl]-2-propenylimino-N-[1-(1-naphthyl)ethylamine (IV) with a sequential addition of:—a solution of sodium borohydride, methanol and a base,—oxalic acid and—a base to obtain (R)—N-[3-[3-(trifluoromethyl)phenyl]-2-propenyl]-1-(1-naphthyl)ethylamine (V) by passing through the precipitation of the oxalate salt of compound (V) after the addition of oxalic acid; c) hydrogenating (R)—N-[3-[3-(trifluoromethyl)phenyl]-2-propenyl]-1-(1-naphthyl)ethylamine (V) thus obtaining (R)—N-(3-(3-(trifluoromethyl)phenyl]propyl]-1-(1-naphthyl)ethylamine cinacalcet base (VI), which is retaken in ethyl acetate; and d) treating the solution of cinacalcet base (VI) in ethyl acetate with hydrochloric acid to afford cinacalcet hydrochloride (I). Preferably, the step a) of reacting (R)-(+)-1-(1-naphthyl)ethylamine (II) with 3-[3-(trifluoromethyl)phenyl]propenaldehyde (III) to afford the non isolated intermediate (R)—N-[3-[3-(trifluoromethyl)phenyl]-2-propenylimino-N-[1-(1-naphthyl)ethylamine (IV) occurs in the presence of methanol.

Provenance & Evidence