WO2013075679A1 - A method of producing cinacalcet - Google Patents
A method of producing cinacalcet Download PDFInfo
- Publication number
- WO2013075679A1 WO2013075679A1 PCT/CZ2012/000119 CZ2012000119W WO2013075679A1 WO 2013075679 A1 WO2013075679 A1 WO 2013075679A1 CZ 2012000119 W CZ2012000119 W CZ 2012000119W WO 2013075679 A1 WO2013075679 A1 WO 2013075679A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cinacalcet
- formula
- catalyst
- pharmaceutically acceptable
- trifluoromethyl
- Prior art date
Links
- VDHAWDNDOKGFTD-MRXNPFEDSA-N cinacalcet Chemical compound N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 VDHAWDNDOKGFTD-MRXNPFEDSA-N 0.000 title claims abstract description 30
- 229960003315 cinacalcet Drugs 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 26
- 239000003054 catalyst Substances 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- QWXKQVIMGVVIBX-UHFFFAOYSA-N 3-[3-(trifluoromethyl)phenyl]propan-1-ol Chemical compound OCCCC1=CC=CC(C(F)(F)F)=C1 QWXKQVIMGVVIBX-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000029936 alkylation Effects 0.000 claims abstract description 9
- 238000005804 alkylation reaction Methods 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- RTCUCQWIICFPOD-SECBINFHSA-N (1r)-1-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C([C@H](N)C)=CC=CC2=C1 RTCUCQWIICFPOD-SECBINFHSA-N 0.000 claims description 4
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 4
- MMAGMBCAIFVRGJ-UHFFFAOYSA-J iridium(3+);1,2,3,4,5-pentamethylcyclopenta-1,3-diene;tetrachloride Chemical compound Cl[Ir+]Cl.Cl[Ir+]Cl.CC=1C(C)=C(C)[C-](C)C=1C.CC=1C(C)=C(C)[C-](C)C=1C MMAGMBCAIFVRGJ-UHFFFAOYSA-J 0.000 claims description 3
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 abstract description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 229960000478 cinacalcet hydrochloride Drugs 0.000 description 4
- QANQWUQOEJZMLL-PKLMIRHRSA-N cinacalcet hydrochloride Chemical compound Cl.N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 QANQWUQOEJZMLL-PKLMIRHRSA-N 0.000 description 4
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- -1 cyanoborohydride Chemical compound 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- APCCHYPQHODSBD-UHFFFAOYSA-N 3-[3-(trifluoromethyl)phenyl]propanal Chemical compound FC(F)(F)C1=CC=CC(CCC=O)=C1 APCCHYPQHODSBD-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- KSBWHDDGWSYETA-SNAWJCMRSA-N (E)-3-(trifluoromethyl)cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC(C(F)(F)F)=C1 KSBWHDDGWSYETA-SNAWJCMRSA-N 0.000 description 1
- LAXRNWSASWOFOT-UHFFFAOYSA-J (cymene)ruthenium dichloride dimer Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ru+2].[Ru+2].CC(C)C1=CC=C(C)C=C1.CC(C)C1=CC=C(C)C=C1 LAXRNWSASWOFOT-UHFFFAOYSA-J 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- NNMBNYHMJRJUBC-UHFFFAOYSA-N 1-bromo-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(Br)=C1 NNMBNYHMJRJUBC-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- YLTJJMIWCCJIHI-UHFFFAOYSA-N 3-[3-(trifluoromethyl)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=CC(C(F)(F)F)=C1 YLTJJMIWCCJIHI-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000003975 aryl alkyl amines Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- VOHVDFZCBGKYSV-GFCCVEGCSA-N n-[(1r)-1-naphthalen-1-ylethyl]prop-2-en-1-amine Chemical compound C1=CC=C2C([C@H](NCC=C)C)=CC=CC2=C1 VOHVDFZCBGKYSV-GFCCVEGCSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/14—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of hydroxy groups or of etherified or esterified hydroxy groups
- C07C209/16—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of hydroxy groups or of etherified or esterified hydroxy groups with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
Definitions
- the invention relates to a method of producing Cinacalcet of formula I, chemically N-[(1R)-1- (naphthyl)ethyl]-3-[3-(trifluoromethyl)-phenyl]propane-l -amine, and its pharmaceutically acceptable salts, for instance hydrochloride.
- Cinacalcet in the form of its hydrochloride is being sold under the trademark Mimpara. It has been approved for therapy of secondary hyperparathyreosis in dialysed patients with kidney disease and also in therapy of hypercalcemia in patients with parathyroid cancer.
- US patent 6,011 ,068 discloses a group of arylalkylamines, in which Cinacalcet and generally its pharmaceutically acceptable salts are also included.
- US patent 6,21 1 ,244 specifically describes Cinacalcet.
- This patent also shows possible synthesis of substances with structure analogous to that of Cinacalcet using reductive amination consisting in coupling the respective aromatic aldehyde or ketone with a suitable arylamine, followed by reduction with a hydride agent.
- the amine can also be coupled with a nitrile in presence of diisobutyl aluminium hydride, which leads to preparation of the respective imine, which is again reduced. This process is described in US patent 5,504,253.
- Cinacalcet described in Drugs of the Future 2002, 27(9), 831-836, comprises reaction of (R)-(l -naphthyl)ethylamine with 3-[3-(trifluoromethyl)phenyl]- propionaldehyde in the presence of titanium tetraisopropoxide to form the respective imine, which is finally reduced by cyanoborohydride in ethanol (see Scheme 1).
- Patent application WO 2008/035212 discloses an alternative procedure of preparing 3-[3-(trifluoromethyl)phenyl]propionaldehyde by oxidation of the respective alcohol with the radical agent TEMPO.
- Cinacalcet Another possibility of preparing Cinacalcet mentioned in US patent 7,250,533 consists in conversion of the alcoholic group of 3-[3-(trifluoromethyl)phenyl]propanol to a well leaving group and subsequent N-alkylation of (R)-(l-naphthyl)ethylamine, as depicted in the following Scheme 2.
- Scheme 3 :
- This invention provides a new efficient procedure of producing Cinacalcet of formula I
- This invention provides a new efficient procedure of producing Cinacalcet of formula I
- catalysts based on a transition metal such as, for instance, Fe, Cu, Au, Pd, Ru, Rh, Re, Ir.
- the catalyst is used in an amount of 0.4 to 5 mol % based on the starting substance.
- the alkylation is performed in an inert organic solvent, such as, for instance, aromatic hydrocarbons, in particular toluene.
- the reaction is carried out in the temperature interval of 80 to 130 °C, preferably at temperatures of 100 to 1 10 °C.
- the respective salt is prepared without isolating the base.
- the Cinacalcet salt is prepared, which directly crystallizes from the reaction mixture or a suitable co-solvent is added before the crystallization.
- the alkylation is carried out in toluene in the presence of a catalyst, which is [dichloro(pentamethylcyclopentadienyl)iridium(III) dimer], at temperature of 100 to 1 10°C.
- a catalyst which is [dichloro(pentamethylcyclopentadienyl)iridium(III) dimer]
- the reaction mixture is then diluted with a co-solvent, which is ethyl acetate, and hydrogen chloride in an organic solvent, for instance in ether, is added to the reaction mixture.
- the respective hydrochloride is isolated from the reaction mixture in the yield of 75 % and HPLC purity higher than 99.5 %. If necessary, the product can be crystallized, for instance from ethyl acetate.
- the new method of producing Cinacalcet and its salts is a one-step one; unlike in the prior procedures, the alkylation does not require conversion of the poorly reactive hydroxyl group to another better leaving group and allows obtaining Cinacalcet and its salts in a high yield and in a purity suitable for pharmaceutical use.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201280057515.4A CN103958456B (zh) | 2011-11-25 | 2012-11-21 | 制备西那卡塞的方法 |
| BR112014012434A BR112014012434A2 (pt) | 2011-11-25 | 2012-11-21 | método de produção de cinacalcet, e, uso cinacalcet |
| HU1400341A HUP1400341A3 (en) | 2011-11-25 | 2012-11-21 | A method of producing cinacalcet |
| IN1319KON2014 IN2014KN01319A (cs) | 2011-11-25 | 2012-11-21 | |
| IL232678A IL232678A (en) | 2011-11-25 | 2014-05-18 | METHOD FOR PRODUCING SYNACLETZ |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZPV2011-770 | 2011-11-25 | ||
| CZ20110770A CZ303627B6 (cs) | 2011-11-25 | 2011-11-25 | Zpusob výroby Cinacalcetu |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013075679A1 true WO2013075679A1 (en) | 2013-05-30 |
Family
ID=47435672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CZ2012/000119 WO2013075679A1 (en) | 2011-11-25 | 2012-11-21 | A method of producing cinacalcet |
Country Status (7)
| Country | Link |
|---|---|
| CN (1) | CN103958456B (cs) |
| BR (1) | BR112014012434A2 (cs) |
| CZ (1) | CZ303627B6 (cs) |
| HU (1) | HUP1400341A3 (cs) |
| IL (1) | IL232678A (cs) |
| IN (1) | IN2014KN01319A (cs) |
| WO (1) | WO2013075679A1 (cs) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5504253A (en) | 1994-07-15 | 1996-04-02 | Nps Pharmaceuticals, Inc. | Amine preparation |
| US6011068A (en) | 1991-08-23 | 2000-01-04 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US6211244B1 (en) | 1994-10-21 | 2001-04-03 | Nps Pharmaceuticals, Inc. | Calcium receptor-active compounds |
| US7250533B2 (en) | 2005-05-16 | 2007-07-31 | Teva Pharmaceutical Industries Ltd | Process for preparing Cinacalcet hydrochloride |
| US20070259964A1 (en) | 2006-04-27 | 2007-11-08 | Revital Lifshitz-Liron | Process for the preparation of cinacalcet base |
| WO2008035212A2 (en) | 2006-06-08 | 2008-03-27 | Medichem, S.A. | Processes for preparing intermediate compounds useful for the preparation of cinacalcet |
| US7393967B2 (en) | 2006-04-27 | 2008-07-01 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of cinacalcet base |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1883618B1 (en) * | 2005-05-23 | 2009-10-14 | Teva Pharmaceutical Industries Ltd. | Processes for preparing cinacalcet hydrochloride crystal form i |
| JP5358566B2 (ja) * | 2007-06-21 | 2013-12-04 | アムジエン・インコーポレーテツド | シナカルセトおよびその塩を合成する方法 |
| BRPI0919635B8 (pt) * | 2008-10-28 | 2021-05-25 | Fis Fabbrica Italiana Sintetici Spa | processo para preparação de cinacalcet |
-
2011
- 2011-11-25 CZ CZ20110770A patent/CZ303627B6/cs not_active IP Right Cessation
-
2012
- 2012-11-21 BR BR112014012434A patent/BR112014012434A2/pt not_active IP Right Cessation
- 2012-11-21 IN IN1319KON2014 patent/IN2014KN01319A/en unknown
- 2012-11-21 CN CN201280057515.4A patent/CN103958456B/zh active Active
- 2012-11-21 WO PCT/CZ2012/000119 patent/WO2013075679A1/en active Application Filing
- 2012-11-21 HU HU1400341A patent/HUP1400341A3/hu unknown
-
2014
- 2014-05-18 IL IL232678A patent/IL232678A/en active IP Right Grant
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6011068A (en) | 1991-08-23 | 2000-01-04 | Nps Pharmaceuticals, Inc. | Calcium receptor-active molecules |
| US5504253A (en) | 1994-07-15 | 1996-04-02 | Nps Pharmaceuticals, Inc. | Amine preparation |
| US6211244B1 (en) | 1994-10-21 | 2001-04-03 | Nps Pharmaceuticals, Inc. | Calcium receptor-active compounds |
| US7250533B2 (en) | 2005-05-16 | 2007-07-31 | Teva Pharmaceutical Industries Ltd | Process for preparing Cinacalcet hydrochloride |
| US20070259964A1 (en) | 2006-04-27 | 2007-11-08 | Revital Lifshitz-Liron | Process for the preparation of cinacalcet base |
| US7393967B2 (en) | 2006-04-27 | 2008-07-01 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of cinacalcet base |
| WO2008035212A2 (en) | 2006-06-08 | 2008-03-27 | Medichem, S.A. | Processes for preparing intermediate compounds useful for the preparation of cinacalcet |
Non-Patent Citations (4)
| Title |
|---|
| DRUGS OF THE FUTURE, vol. 27, no. 9, 2002, pages 831 - 836 |
| SORBERA L A ET AL: "Cinacalcet hydrochloride", DRUGS OF THE FUTURE, PROUS SCIENCE, ES, vol. 27, no. 9, 1 January 2002 (2002-01-01), pages 831 - 836, XP002403819, ISSN: 0377-8282, DOI: 10.1358/DOF.2002.027.09.695016 * |
| TETRAHEDRON LETTERS, 2004, pages 8355 - 8358 |
| TETRAHEDRON LETTERS, 2008, pages 13 - 15 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL232678A (en) | 2017-05-29 |
| HUP1400341A3 (en) | 2014-12-29 |
| CN103958456B (zh) | 2015-10-21 |
| IL232678A0 (en) | 2014-08-03 |
| HUP1400341A2 (en) | 2014-10-28 |
| IN2014KN01319A (cs) | 2015-10-16 |
| CN103958456A (zh) | 2014-07-30 |
| CZ2011770A3 (cs) | 2013-01-16 |
| BR112014012434A2 (pt) | 2017-06-06 |
| CZ303627B6 (cs) | 2013-01-16 |
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