Process for preparing Cinacalcet hydrochloride
AssigneeZach System S.P.A.
InventorsNicola Catozzi, Livius Cotarca, Johnny Foletto, Massimiliano Forcato, Roberto Giovanetti, Giorgio Soriato, Massimo Verzini
Life of this patent
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Abstract
A process for preparing N-[(1R)-1-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)-phenyl]propan-1-amine hydrochloride salt of formula (I) i.e. Cinacalcet hydrochloride and its intermediates of formulae (VII) and (VIII) wherein Z is chloride or another pharmaceutically acceptable anionic counterion.
Claims12
A method for preparing Cinacalcet hydrochloride of formula (I)
- which comprises the steps of:
- e) reducing a compound of formula (VII)
- wherein Z is chloride or another pharmaceutically acceptable anionic counterion, to obtain a compound of formula (Ia)
- wherein Z is as defined above and, when in a compound of formula (Ia) Z is a pharmaceutically acceptable anionic counterion different from chloride,
- f) converting said compound of formula (Ia) to Cinacalcet hydrochloride of formula (I),
- wherein when in the compound of formula (VII) Z is chloride, the compound has formula (VIIa)
- said compound of formula (VIIa) being obtained with a process comprising the step of:
- g) converting a compound of formula (VII)
- wherein Z is a pharmaceutically acceptable anionic counterion different from chloride;
- said compound of formula (VII), wherein Z is a pharmaceutically acceptable anionic counterion different from chloride, being obtained with a process comprising the step of:
- j) eliminating sulfuric acid from the compound of formula (VIII)
- wherein the wavy line represents a bond connected to carbon having R or S configuration, with a strong acid, neutralizing and acidifying with an acid HZ, wherein Z is a pharmaceutically acceptable anionic counterion different from chloride.
A method for preparing Cinacalcet intermediate of formula (VIII)
- wherein the wavy line represents a bond connected to carbon having R or S configuration, which comprises the steps of:
- k) reducing the compound of formula (V)
- to the corresponding benzylic alcohol of formula (Va)
- wherein [ ] means that the compound of formula (Va) can be isolated or not from the reaction mixture, in the presence of a reducing agent or by mean of a catalytic hydrogenation process, and
- l) converting the compound of formula (Va) in the sulfate ester of formula (VIII).
A method for preparing Cinacalcet hydrochloride of formula (I)
- which comprises the steps of
- k) reducing the compound of formula (V)
- to the corresponding benzylic alcohol of formula (Va)
- wherein [ ] means that the compound of formula (Va) can be isolated or not from the reaction mixture, in the presence of a reducing agent or by mean of a catalytic hydrogenation process,
- l) converting the compound of formula (Va) into the sulfate ester of formula (VIII)
- wherein the wavy line represents a bond connected to carbon having R or S configuration,
- j) eliminating sulfuric acid from the compound of formula (VIII) with a strong acid, neutralizing and acidifying with the H2SO4 to give the compound of formula (VIIb)
- g) converting the compound (VIIb) into the compound (VIIa) and
- e) reducing the compound (VIIa) to Cinacalcet hydrochloride of formula (I).
Cinacalcet intermediate having the following formula (VIII)
- wherein the wavy line represents a bond connected to carbon having R or S configuration.
Dependencies are inferred from the claim text.