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WO2014178068A2 - Procédé perfectionné pour la préparation de n-[1-(1-naphtyl)éthyl]-3-[3-(trifluorométhyl)phényl]propan-1-amine et de ses sels pharmaceutiquement acceptables - Google Patents

Procédé perfectionné pour la préparation de n-[1-(1-naphtyl)éthyl]-3-[3-(trifluorométhyl)phényl]propan-1-amine et de ses sels pharmaceutiquement acceptables Download PDF

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Publication number
WO2014178068A2
WO2014178068A2 PCT/IN2014/000219 IN2014000219W WO2014178068A2 WO 2014178068 A2 WO2014178068 A2 WO 2014178068A2 IN 2014000219 W IN2014000219 W IN 2014000219W WO 2014178068 A2 WO2014178068 A2 WO 2014178068A2
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Prior art keywords
formula
naphthyl
ethylamine
cinacalcet
ethyl
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PCT/IN2014/000219
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WO2014178068A3 (fr
Inventor
Shri Prakash Dhar Dwivedi
Ashok Prasad
Jitesh Amratlal DESAI
Ankur Vinodbhai NAIK
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Zydus Lifesciences Ltd
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Cadila Healthcare Ltd
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Priority claimed from IN1336MU2013 external-priority patent/IN2013MU01336A/en
Publication of WO2014178068A2 publication Critical patent/WO2014178068A2/fr
Publication of WO2014178068A3 publication Critical patent/WO2014178068A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/24—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds
    • C07C209/26—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds by reduction with hydrogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/82—Purification; Separation; Stabilisation; Use of additives
    • C07C209/86—Separation
    • C07C209/88—Separation of optical isomers

Definitions

  • the present invention relates to an improved process for preparation of N- [ 1 -( 1 -naphthyl)ethyl] -3 - [3 -(trifluoromethyl)phenyl]propan- 1 -amine and pharmaceutically acceptable salts thereof.
  • the present invention relates to an improved process for preparation cinacalcet or pharmaceutically acceptable salts and intermediates thereof.
  • Cinacalcet (approved as its HCl salt) is known to be useful for the treatment of hyperparathyroidism and the preservation of bone density in patients with kidney failure or hypercalcemia due to cancer. It is marketed as SensiparTM in the USA and as MimparaTM in Europe. Chemically cinacalcet hydrochloride is (R)-N- [ 1 -( 1 -naphthyl)ethyl] -3 - [3 -(trifluoromethyl)phenyl]propan- 1 -amine,
  • hydrochloride which is represented as Formula-la.
  • U.S. PG-Pub. No. 2012/0053362 Al discloses the preparation of salt of (R)- or (S)-isomer of 1 -naphthylethylamine with mandelic acid and its use in the preparation of cinacalcet.
  • solid state form of R-(+)-l-(l- naphthyl) ethylamine tartrate of Formula (II) which is characterized by XRD and IR.
  • a solid state form of R-(+)-l-(l- naphthyl) ethylamine tartrate of Formula (II) is having chiral purity greater than about 99.8% as measured by HPLC.
  • step (b) converting racemic l-(l-naphthyl)ethylamine into desired R-(+)-l-(l- naphthyl) ethylamine and recycling the undesired S-(-)-l-(l-naphthyl) ethylamine as in step (a).
  • cinacalcet hydrochloride of Formula (la) having purity of greater than about 99%, specifically greater than about 99.5%, more specifically greater than about 99.9%, and most specifically greater than about 99.98% and having all other impurities less than 0.1% as measured by HPLC.
  • FIGURE-1 Illustrated X-ray diffractogram (XRD) of cinacalcet hydrochloride Form-I.
  • FIGURE-2 Illustrated X-Ray diffraction (XRD) pattern of R-(+)-l-(l-naphthyl) ethyl amine tartrate of Formula (II) in solid state form.
  • XRD X-Ray diffraction
  • FIGURE-3 Illustrated infra-red (IR) spectrum of R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II) in solid state form.
  • IR infra-red
  • the present invention relates to an improved process for the preparation of N-[l-(l-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]propan-l -amine (cinacalcet) of Formula (I), which is commercially available as (R)-cinacalcet hydrochloride (la)
  • pharmaceutically acceptable salt is selected from a hydrochloride salt, a hydrobromide salt, an oxalate salt, a maleate salt, a fumarate salt, a besylate salt, a tosylate salt or a tartrate salt.
  • the suitable solvent for step (a) is selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohol, ketones, ester and the like.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, C1-C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the likes.
  • the solvent may be methanol.
  • the suitable metal catalyst as a reducing agent under hydrogen pressure in step (a) may be selected from Raney-Ni, Pd/C, Pt/C and Rh/C.
  • the preferred metal catalyst may be Raney-Ni.
  • the suitable salt of step (b) is selected from hydrochloride, hydrobromide, oxalate, maleate, fumarate, tartrate.
  • the salt may be hydrochloride.
  • the suitable organic solvent for step (b) is selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohol, ketones, ester and the like.
  • the suitable solvent comprises toluene, xylene, ethylbenzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, Ci- C 4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the likes.
  • the solvent may be methanol.
  • the suitable solvent for condensation of compound of Formula (A) and Formula (B) is selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohol, ketones, ester and the like.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, Q-C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the likes.
  • the solvent may be methanol.
  • the suitable organic solvent for step (a) is selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohol, ketones, ester and the like.
  • the suitable solvent comprises ester solvents selected form ethyl acetate, isopropyl acetate, ethyl butyrate etc.
  • the solvent may be ethyl acetate.
  • a X-Ray diffraction pattern of crystalline Form-I of cinacalcet hydrochloride substantially as depicted in Fig. 1.
  • the solid state form of R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II) is characterized by at least one or more of the following properties:
  • an IR spectrum having absorption bands at about 3653, 3396, 3319, 2997, 2721, 2509, 1708, 1597, 1525, 1442, 1400, 1303, 1263, 1120, 1066, 991, 894, 869, 842, 806, 788, 680, 615, 570, 520, 478, 441 and 414 ⁇ 2 cm "1 .
  • a solid state form of R-(+)-l-(l- naphthyl) ethylamine tartrate of Formula (II) is having chiral purity greater than about 99.8% as measured by HPLC.
  • the suitable organic solvent for step (a) comprises one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, C1-C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • solvent may be mixture of methanol-water.
  • racemic l-(l-naphthyl) ethylamine with D-(-)-tartaric acid may be reacted at a mole ratio in the range from 1 :05 to 1 :2. Particularly the molar ratio may be 1 : 1.
  • the suitable temperature range for the reaction in step (a) may be 25°C to 90°C.
  • the preferred temperature range may be 55 to 65°C.
  • R-(+)-l-(l-naphthyl)ethylamine tartrate of Formula (II) in a solid state form may be isolated from a suitable solvent selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the solvent may be methanol.
  • an improved process for preparing cinacalcet of Formula I or pharmaceutically acceptable salts thereof comprising the steps of:
  • R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II) may be converted to R-(+)-l-(l-naphthyl)ethylamine of Formula (A) in a suitable organic solvent selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, C C 4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • solvent may be water and toluene.
  • R-(+)-l -(l-naphthyl)ethylamine tartrate of Formula (II) may be converted to R-(+)-l-(l-naphthyl)ethylamine of Formula (A) using a suitable base selected from alkali and alkaline metal hydroxides and carbonates, preferably sodium hydroxide.
  • R-(+)-l -(l-naphthyl) ethylamine of Formula (A) obtained in step (i) may be isolated or in-situ treated with 3-(3-(trifluoromethyl) phenyl) propanal of Formula (B) for the formation of cinacalcet of Formula I or pharmaceutically acceptable salts thereof.
  • the suitable organic solvent for step (b) may be selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the solvent may be methanol.
  • the metal catalyst as a reducing agent under hydrogen pressure in step (b) may be selected from Raney-Ni, Pd/C, Pt/C, Rh C.
  • the preferred metal catalyst may be Raney-Nickel.
  • the suitable organic solvent for converting cinacalcet into its pharmaceutically acceptable salts in step (c) may be selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the solvent may be methanol.
  • the suitable organic solvent for step (a) may be selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, C1-C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • solvent may be mixture of methanol-water.
  • R-(+)-l -(l-naphthyl)ethylamine tartrate of Formula (II) in a solid state may be isolated from a suitable solvent selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the solvent may be methanol.
  • (R)-(+)-(l-naphthyl)ethylamine tartrate of Formula (II) may be converted into (R)-(+)-(l-naphthyl)ethylamine of Formula (A) in a suitable organic solvent selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, C1-C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • solvent may be water and toluene.
  • (R)-(+)-(l-naphthyl)ethylamine tartrate of Formula (II) may be converted into (R)-(+)-(l -naphthyl)ethylamine of Formula (A) using a suitable base selected from alkali and alkaline metal hydroxides and carbonates, preferably sodium hydroxide.
  • step (b) converting racemic l-(l-naphthyl)ethylamine into desired R-(+)-l-(l- naphthyl) ethylamine and recycling the undesired S-(-)-l-(l - naphthyl)ethylamine as in step (a).
  • the suitable solvent for step (a) comprises one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters, ethers or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, dimethyl formamide, ethylene glycol, diethylene glycol, polyethylene glycol (PEG), dimethyl acetamide, dimethyl sulfoxide (DMSO), methylene dichloride, acetonitrile, Cj-C 4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • the solvent may be dimethyl sulfoxide (DMSO).
  • the base for step (a) may be selected from alkali and alkaline metal hydroxides and carbonates, preferably sodium hydroxide.
  • the suitable organic solvent for converting racemic l-(l-naphthyl) ethylamine in to R-(+)-l-(l-naphthyl) ethylamine in step (b) may be selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, C(-C straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • solvent may be mixture of methanol-water.
  • an improved process for preparing cinacalcet of le salts thereof comprising the steps of:
  • the suitable organic solvent for step (a) may be selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, d-C 4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • solvent may be mixture of methanol-water.
  • R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II) may be converted in to into R-(+)-l-(l-naphthyl) ethylamine of Formula (A) in a suitable organic solvent selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof.
  • the suitable solvent comprises toluene, xylene, ethyl benzene dimethyl formamide, dimethyl acetamide, methylene dichloride, acetonitrile, Q-C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and the like.
  • solvent may be water and toluene.
  • R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II) may be converted in to into R-(+)-l -(l-naphthyl) ethylamine of Formula (A) using a suitable base selected from alkali and alkaline metal hydroxides and carbonates, preferably sodium hydroxide.
  • the suitable organic solvent for step (c) may be selected from may be selected from one or more of hydrocarbons, halogenated solvents, nitriles, amides, alcohols, ketones, esters or a mixture thereof. Particularly, the solvent may be methanol.
  • the metal catalyst as a reducing agent under hydrogen pressure in step (c) may be selected from Raney-Ni, Pd/C, Pt/C, Rh/C.
  • the preferred metal catalyst may be Raney-Nickel.
  • cinacalcet hydrochloride of Formula (la) having purity of greater than about 99%, specifically greater than about 99.5%, more specifically greater than about 99.9%, and most specifically greater than about 99.98% and having all other impurities less than 0.1% as measured by HPLC.
  • Cinacalcet Hydrochloride (la when HX is HCI)
  • Example 1 Preparation of R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II) - Water (500 ml) and methanol (400 ml) were added in a RBF at 25°C to 35°C followed by addition of D-(-)-tartaric acid (87.60 g). The reaction mass was heated at 60°C to 65 °C and racemic l-(l-Naphthyl) ethyl amine (100 g) and methanol (100 ml) was added. The reaction mass was maintained for 10 hours. The reaction mass was filtered at 60-65°C and washed with 50% aq. methanol (100 mL).
  • Example 2 Preparation of R-(+)-l-(l-naphthyI) ethylamine tartrate of Formula (II) - Water (500 ml) and methanol (400 ml) were added in a RBF at 25°C to 35°C followed by addition of D-(-)-tartaric acid (83.26 g). The reaction mass was heated at 60°C to 65 °C and racemic l-(l-Naphthyl) ethyl amine (100 g) in methanol (100 ml) was added. The reaction mass was maintained for 10 hours. The reaction mass was filtered at 60°C to 65°C and washed with 50% aq.
  • Example 3 Preparation of R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II) - Water (500 ml) and methanol (400 ml) were added in a RBF at 25°C to 35°C followed by addition of D-(-)-tartaric acid (87 g). The reaction mass was heated at 60°C to 65°C and racemic l-(l-Naphthyl) ethyl amine (100 g) in methanol (100 ml) was added. The reaction mass was maintained for 15 hours. The reaction mass was cooled to 55°C to 60°C and washed with 50% aq. methanol (100 ml) afforded R-(+)-l-(l-naphthyl) ethylamine tartrate of Formula (II). (Chiral Purity >82%).
  • Example 4 Preparation of cinacalcet hydrochloride of Formula (la) - Water (90 ml), R-(+)-l-(l-Naphthyl)ethylamine tartrate of Formula (II) (30 g) and toluene (90 ml) were added in a RBF at 25°C to 35°C. The pH of reaction mass was adjusted to 12.5 to 13.5 by adding 10% NaOH solution and stirred for 30 minutes. Toluene layer was separated and toluene was distilled out under vacuum below 70°C to afford R-(+)-l-(l-naphthyl) ethylamine.
  • Residue was cooled to 25°C to 35°C and methanol (200) was added and reaction mass was transferred in to autoclave (2 L). The reaction mass was stirred for 30 minutes. Raney-Ni (2 g) was added under Nitrogen. Nitrogen pressure of 2-3 Kg/cm 2 was applied and released and was repeated. The reaction mass was hydrogenated at 50°C to 55°C and maintained for 6 to 8 hours. Pressure was released and reaction mass was filtered through Hyflow bed and washed with methanol (20 ml). The pH of reaction mass was adjusted between 1 to 2 with cone. HC1 (10-15 ml) and methanol was distilled out under vacuum below 50°C.
  • reaction mass was heated to 35°C to 45°C and further cooled to 25°C to 35°C.
  • the reaction mass was filtered and washed with 50 % aqueous methanol (2x10 ml) and treated with water (100 ml) and maintained for 45 minutes.
  • the reaction mass was filtered and washed with water (2 x 10 ml) afforded cinacalcet hydrochloride of Formula (la) which was treated with ethyl acetate (1200 mL) at 25°C to 35°C.
  • the reaction mass was heated at 70°C to 80°C and maintained for 30 minutes and treated with activated charcoal (3 g).
  • the reaction mass was filtered and washed with ethyl acetate (50 ml). The reaction mass , was concentrated till 700 mL ethyl acetate remained. The reaction mass was cooled to 15°C to 20°C and stirred for 90 mintues. The reaction mass was filtered and washed with ethyl acetate afforded cinacalcet hydrochloride of Formula (la). (Purity> 99.9% by HPLC).
  • Example-5 Preparation of N-[l-(l-naphthyl)ethyl]-3-[3-(trifluoromethyl) phenyl]propan-l-amine hydrochloride (cinacalcet hydrochloride) of Formula-(Ia) - 17 g of (R)-l-(naphthalen-l-yl)ethanamine of Formula (A) is charged in a Autoclave containing methanol (200 ml). To the same 20 g 3-(3- (trifluoromethyl)phenyl) propanal of Formula (B) was added at temperature ranging from 25°C to 35°C.
  • Example-6 Purification of cinacalcet hydrochloride of Formula-(Ia) - lOg of Cinacalcet hydrochloride was charged in a RBF containing 70 mL of acetone at temperature ranging from 25°C to 35°C. Reaction mass was heated to 50°C to 55°C and stirred for one hour. The reaction mass was cooled and product was filtered off. The solid was washed and dried to yield 70 % to 90% of the pure title compound.
  • Example-7 Preparation of crystalline Form-I of cinacalcet hydrochloride of Formula-(Ia) - lOg of Cinacalcet hydrochloride was charged in a RBF containing 120 ml of ethyl acetate at temperature ranging from 25°C to 35°C. Reaction mass was heated to 70°C to 80°C and stirred. The reaction was filter at the same temperature. The reaction mass was cooled and product was filtered off. The solid was washed with ethyl acetate and dried to yield 80 % to 98% of the pure title compound.

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention porte sur un procédé perfectionné pour la préparation de N-[1-(1-naphtyl)éthyl]-3-[3-(trifluorométhyl)phényl]propan-1-amine et de ses sels pharmaceutiquement acceptables. En particulier, la présente invention porte sur un procédé perfectionné pour la préparation de cinacalcet ou de ses sels pharmaceutiquement acceptables et sur des intermédiaires s'y rapportant.
PCT/IN2014/000219 2013-04-08 2014-04-08 Procédé perfectionné pour la préparation de n-[1-(1-naphtyl)éthyl]-3-[3-(trifluorométhyl)phényl]propan-1-amine et de ses sels pharmaceutiquement acceptables Ceased WO2014178068A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN1336/MUM/2013 2013-04-08
IN2925MU2013 2013-09-11
IN2925/MUM/2013 2013-09-11
IN1336MU2013 IN2013MU01336A (fr) 2013-04-08 2014-04-08

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WO2014178068A2 true WO2014178068A2 (fr) 2014-11-06
WO2014178068A3 WO2014178068A3 (fr) 2014-12-18

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021176381A1 (fr) * 2020-03-04 2021-09-10 Embio Limited Procédé de préparation de sels de lactate diastéréomériques de 1-(1-naphtyl)éthyl amine et d'énantiomères purs de 1-(1-naphtyl)éthyl amine

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0313661D0 (en) * 2003-06-13 2003-07-16 Avecia Ltd Process
EP2041065A2 (fr) * 2006-06-08 2009-04-01 Medichem, S.A. Procédé de fabrication du chlorhydrate de cinacalcet et formes polymorphes de celui-ci
US8575393B2 (en) * 2009-03-05 2013-11-05 Cipla Limited Process for the preparation of cinacalcet and salts thereof, and intermediates for use in the process
IT1396623B1 (it) * 2009-11-26 2012-12-14 Dipharma Francis Srl Procedimento per la preparazione di cinacalcet e suoi intermedi
CN103420845B (zh) * 2013-08-21 2015-09-02 中国药科大学 一种制备西那卡塞中间体r-(+)-1-(1-萘基)乙胺的方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021176381A1 (fr) * 2020-03-04 2021-09-10 Embio Limited Procédé de préparation de sels de lactate diastéréomériques de 1-(1-naphtyl)éthyl amine et d'énantiomères purs de 1-(1-naphtyl)éthyl amine

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