Cinacalcet Hydrochloride → 1-(1-Naphthyl)ethylamine
Reaction equation
[CH3:1][C@@H:2]([NH:13]CCCC1C=CC=C(C(F)(F)F)C=1)[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=12.Cl.C1([C@H](N)C)C2C(=CC=CC=2)C=CC=1.FC(F)(F)C1C=C(C=CC=O)C=CC=1>>[C:3]1([CH:2]([NH2:13])[CH3:1])[C:8]2[C:7](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=1Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-c4ef202985914de4a38172e3bc054feb
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08614354B2
Reaction notes
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