NO320810B1 - Fremgangsmate for fremstilling av forbindelser og forbindelsene (S)-1-fenyl-2-(2-pyridyl)etanamin og (S)-fenyl-2-(2-pyridyl)etanamin (S)-malatsalt. - Google Patents
Fremgangsmate for fremstilling av forbindelser og forbindelsene (S)-1-fenyl-2-(2-pyridyl)etanamin og (S)-fenyl-2-(2-pyridyl)etanamin (S)-malatsalt. Download PDFInfo
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- NO320810B1 NO320810B1 NO20014889A NO20014889A NO320810B1 NO 320810 B1 NO320810 B1 NO 320810B1 NO 20014889 A NO20014889 A NO 20014889A NO 20014889 A NO20014889 A NO 20014889A NO 320810 B1 NO320810 B1 NO 320810B1
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- Prior art keywords
- phenyl
- ethanamine
- pyridyl
- compounds
- compound
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- 238000000034 method Methods 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 4
- 150000001875 compounds Chemical class 0.000 title claims description 25
- FWUQWDCOOWEXRY-ZDUSSCGKSA-N lanicemine Chemical compound C([C@H](N)C=1C=CC=CC=1)C1=CC=CC=N1 FWUQWDCOOWEXRY-ZDUSSCGKSA-N 0.000 title claims description 6
- KRCGPQRORHRZRC-SXWHKFHYSA-N (2s)-2-hydroxybutanedioic acid;(1s)-1-phenyl-2-pyridin-2-ylethanamine Chemical compound OC(=O)[C@@H](O)CC(O)=O.C([C@H](N)C=1C=CC=CC=1)C1=CC=CC=N1 KRCGPQRORHRZRC-SXWHKFHYSA-N 0.000 title claims description 4
- 150000003839 salts Chemical class 0.000 claims description 12
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical group [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims description 8
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 230000003197 catalytic effect Effects 0.000 claims description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 5
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- DZAIOXUZHHTJKN-UHFFFAOYSA-N 2-Desoxy-D-glycero-tetronsaeure Natural products OCC(O)CC(O)=O DZAIOXUZHHTJKN-UHFFFAOYSA-N 0.000 description 1
- NMWDYLYNWRFEMR-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1.CC1=CC=CC=N1 NMWDYLYNWRFEMR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 241000220304 Prunus dulcis Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
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- Cardiology (AREA)
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- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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Description
Foreliggende oppfinnelse angår en forbedret fremgangsmåte for fremstilling av visse forbindelser og (S)-l-fenyl-2-(2-pyridyl)etanamin og (S)-l-fenyl-2-(2-pyridyl)etanamin (S)-malatsalt fremstilt ved fremgangsmåten.
EP 0 633 879 Bl beskriver forbindelser som sies å ha en NMDA reseptor antagonist aktivitet. Forbindelsen kjent som (S)-l-fenyl-2-(2-pyridyl)etanamin er av spesielle interesse, særlig for behandling av slag. Imidlertid lider prosessen som beskrevet i EP 0 633 879 Bl for fremstilling av denne forbindelse, av visse mangler, for eksempel ved at den krever bruken av butyllitium som ikke er gunstig å anvende i stor målestokk.
Det er nå utviklet en ny fremgangsmåte for fremstilling av (S)-l-fenyl-2(2-pyridyl)etanamin som unngår behovet for anvendelse av butyllitium og som derfor er mer egnet for kommersiell anvendelse. Fordi prosessen ifølge oppfinnelsen eliminerer behovet for å anvende butyllitium har den derfor også den ytterligere fordel at den ikke lider under miljøproblemer i forbindelse med butanemisjonen. Videre er det overraskende funnet at fremgangsmåten ifølge oppfinnelsen kan gjennomføres med kun en katalytisk mengde base [i forhold til 2-pikolin med formel (II)] i stedet for en støkiometrisk mengde base som benyttet i EP 0 633 879 Bl. Totalt sett er derfor den her krevede prosess mer effektiv, sikrere, miljømessige gunstige og også rimeligere enn den ifølge EP 0 633 879 Bl.
I et første aspekt tilveiebringer oppfinnelsen derfor en fremgangsmåte for fremstilling av en forbindelse med formel (I) eller et farmasøytisk akseptabelt salt derav:
og som kjennetegnes ved at den omfatter: omsetning av en forbindelse med formel (II) med en forbindelse med formel (III):
i nærvær av et metallheksametyldisilazid og eventuelt derefter oppløsning av enantiomerene av forbindelse (I) og tildanning av et farmasøytisk akseptabelt salt.
En forbindelse med formel (III) kan fremstilles fra benzoaldehyd og et metallheksametyldisilazid, fortrinnsvis litiumheksametyldisilazid (LHMDS). Fortrinnsvis fremstilles forbindelsen med formel (III) ved redusert temperatur, det vil si under 35 °C og fortrinnsvis under 25 °C.
Reaksjonen mellom forbindelsene (II) og (HI) gjennomføres hensiktsmessig ved forhøyt temperatur, for eksempel rundt 40 °C. Reaksjonen kan gjennomføres i et inert opp-løsningsmiddel og fortrinnsvis i et eterisk oppløsningsmiddel som t-butylmetyleter eller helst tetrahydrofuran. Fortrinnsvis er metallheksametyldisilazidet litiumheksametyldisilazid (LHMDS) og denne base benyttes i en katalytisk mengde i forhold til 2-pikolin (2-metylpyridin) med formel (II), for eksempel rundt 10 mol%. Sur opparbeiding av reaksjonsblandingen gir den ønskede forbindelse med formel (I).
Forbindelsene som fremstilles ifølge oppfinnelsen kan danne farmasøytisk akseptable solvater og salter. Forbindelsene med formel (I) kan danne syreaddisjonssalter med syrer, for eksempel konvensjonelle, farmasøytiske akseptable salter med eple-, salt-, hydrobrom-, fosfor-, edikk-, fumar-, salisyl-, sitron-, melke-, mandel-, vin-, trifluoredikk- og metansulfonsyre. Foretrukne salter er malat- og hydrokloridsaltende.
Særlig foretrukne salter er de som kan fremstilles ved bruk av chirale syrer for å gi salter av en enkel enantiomer av forbindelse (I) som beskrevet i EP 0 691 957 Bl. Fortrinnsvis blir den racemiske forbindelse med formel (I) behandlet med (S)-eplesyre for å gi (S)-l-fenyl-2-(2-pyridyl)etanamin (S)-malat.
I et ytterligere aspekt tilveiebringer oppfinnelsen (S)-l-fenyl-2-(2-pyridyl)etanamin og salter derav, særlig (S)-malatsaltet, fremstilt ved bruk av den her beskrevne fremgangsmåte.
Oppfinnelsen skal illustreres ved hjelp av det følgende eksempel.
Eksempel
( S)- a- fenvl- 2- pvridinetanamin ( S)- malat
En oppløsning av litiumheksametyldisilazid (1100 ml av en 1,0 M oppløsning i tetrahydrofuran, 1,1 mol) ble dråpevis og under nitrogen og under avkjøling, satt til en omrørt oppløsning av benzaldehyd (102 ml, 1,0 mol) i 305 ml tetrahydrofuran mens temperaturen ble holdt under 25 °C. Den resulterende oppløsning ble omrørt ved 20 °C i 30 minutter før tilsetning av 2-pikolin (101 ml, 1,0 mol) i en porsjon fulgt av ytterligere 102 ml tetrahydrofuran. Reaksjonsblandingen ble så oppvarmet til 40 °C i løpet av 30 minutter og så holdt ved 40 °C i 90 minutter. Oppløsningen ble så avkjølt til 20 °C i løpet av 10 minutter og dråpevis satt til en oppløsning av konsentrert saltsyre og (420 ml, 5,0 mol) i 900 ml demineralisert vann under avkjøling for å holde temperaturen mellom 10 og 20 °C. Den resulterende blanding, (pH 1) ble omrørt ved 20 °C i 15 minutter hvoretter sjiktene ble separert. Den nedre vandige fase ble separert og vasket med 2 x 900 ml etylacetat og så gjort basisk ved tilsetning av en oppløsning av natrium-hydroksyd (200 g, 5,0 mol) i 830 ml demineralisert vann under avkjøling for å holde temperaturen i området 10 til 20 °C. Den resulterende blanding, (pH 12) ble så omrørt ved 20 °C i 15 minutter og så ekstrahert med 2 x 800 ml etylacetat. Etylacetatopp-løsningen ble så satt til en oppløsning av S-melkesyre (120,7 g 0,9 mol) i 1060 ml etanol, fulgt av poding med 0,2 g av tittelforbindelsen. Denne blanding ble omrørt i 30 minutter ved 20 °C og så avkjølt til 0 °C og omrørt i 20 timer ved 0 °C. Suspensjonen ble filtrert og vasket med 530 ml etanol og man oppnådde et hvitt faststoff som tørket i en vakuumovn ved 40 °C over natten for å gi 119,07 g tilsvarende 35,8% (S)-cc-fenyl-2-pyridinetanamin (S)-malat som et hvitt fast stoff, identiske med kjent materiale.
Claims (7)
1.
En fremgangsmåte for fremstilling av en forbindelse med formel (I) eller et farmasøytisk akseptabelt salt derav:
karakterisert ved at den omfatter: omsetning av en forbindelse med formel (II):
med en forbindelse med formel (III):
i nærvær av et metallheksametyldisilazid og eventuelt derefter oppløsning av enantiomerene av formel (I) og tildanning av et farmasøytisk akseptabelt salt.
2.
Fremgangsmåte ifølge krav 1, karakterisert ved at metallheksametyldisilazidet er litiumheksametyldisilazid.
3.
Fremgangsmåte ifølge krav 1 eller 2, karakterisert v e d at forbindelsene (II) og (HI) omsettes i et eterisk oppløsningsmiddel.
4.
Fremgangsmåte ifølge et hvilket som helst av kravene 1-3, karakterisert ved at litiumheksametyldisilazid benyttes i en katalytisk mengde med henblikk på forbindelsen med formel (II).
5.
Fremgangsmåte ifølge et hvilket som helst av kravene 1-4, karakterisert ved at molforholdet forbindelse (II): litiumheksametyldisilazid er rundt 10:1.
6.
(S)-l-fenyl-2-(2-pyridyl) etanamin eller et salt derav, fremstilt i henhold til fremgangsmåten ifølge et hvilket som helst av kravene 1-5.
7.
(S)-l-fenyl-2-(2-pyridyl) etanamin (S)-malatsalt, fremstilt i henhold til en fremgangsmåte ifølge et hvilket som helst av kravene 1-5.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9901340A SE9901340D0 (sv) | 1999-04-15 | 1999-04-15 | Novel process |
| PCT/SE2000/000713 WO2000063175A2 (en) | 1999-04-15 | 2000-04-14 | Novel process |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20014889D0 NO20014889D0 (no) | 2001-10-08 |
| NO20014889L NO20014889L (no) | 2001-10-08 |
| NO320810B1 true NO320810B1 (no) | 2006-01-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20014889A NO320810B1 (no) | 1999-04-15 | 2001-10-08 | Fremgangsmate for fremstilling av forbindelser og forbindelsene (S)-1-fenyl-2-(2-pyridyl)etanamin og (S)-fenyl-2-(2-pyridyl)etanamin (S)-malatsalt. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6518432B1 (no) |
| EP (1) | EP1492769B1 (no) |
| JP (1) | JP4676064B2 (no) |
| KR (1) | KR100663811B1 (no) |
| CN (1) | CN1138759C (no) |
| AT (1) | ATE333444T1 (no) |
| AU (1) | AU773962B2 (no) |
| BR (1) | BR0009795B1 (no) |
| CA (1) | CA2367410C (no) |
| DE (1) | DE60029493T2 (no) |
| ES (1) | ES2267526T3 (no) |
| IL (2) | IL145585A0 (no) |
| NO (1) | NO320810B1 (no) |
| NZ (1) | NZ514586A (no) |
| SE (1) | SE9901340D0 (no) |
| TW (1) | TWI248433B (no) |
| WO (1) | WO2000063175A2 (no) |
| ZA (1) | ZA200108374B (no) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA106056C2 (uk) | 2008-12-24 | 2014-07-25 | Астразенека Аб | Сполуки 2-метил-1-феніл-2-(піридин-2-іл)пропан-1-аміну та їх застосування для лікування депресії |
| CA2928004C (en) | 2013-11-05 | 2022-04-12 | Astrazeneca Ab | Nmda antagonist prodrugs |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9320273D0 (en) * | 1993-04-01 | 1993-11-17 | Fisons Corp | Compound useful in therapy |
| US5455259A (en) * | 1987-02-06 | 1995-10-03 | Fisons Corporation | Compounds for the treatment of neurodegenerative disorders |
| PT612314E (pt) * | 1991-10-30 | 2000-06-30 | Astra Ab | Derivados de etilamina 2-heterociclicos e seu uso como produtos farmaceuticos |
| KR100259567B1 (ko) | 1992-04-03 | 2000-07-01 | 클래스 빌헬름슨 | 신경변성 질환 치료용 1-페닐-2-(2-피리디닐)에틸아민 에난티오머 |
-
1999
- 1999-04-15 SE SE9901340A patent/SE9901340D0/xx unknown
-
2000
- 2000-04-05 TW TW089106214A patent/TWI248433B/zh not_active IP Right Cessation
- 2000-04-14 JP JP2000612269A patent/JP4676064B2/ja not_active Expired - Fee Related
- 2000-04-14 WO PCT/SE2000/000713 patent/WO2000063175A2/en active IP Right Grant
- 2000-04-14 KR KR1020017013069A patent/KR100663811B1/ko not_active IP Right Cessation
- 2000-04-14 NZ NZ514586A patent/NZ514586A/en not_active IP Right Cessation
- 2000-04-14 ES ES00925816T patent/ES2267526T3/es not_active Expired - Lifetime
- 2000-04-14 AT AT00925816T patent/ATE333444T1/de not_active IP Right Cessation
- 2000-04-14 BR BRPI0009795-0A patent/BR0009795B1/pt not_active IP Right Cessation
- 2000-04-14 EP EP00925816A patent/EP1492769B1/en not_active Expired - Lifetime
- 2000-04-14 CA CA002367410A patent/CA2367410C/en not_active Expired - Fee Related
- 2000-04-14 CN CNB00806198XA patent/CN1138759C/zh not_active Expired - Fee Related
- 2000-04-14 US US09/555,050 patent/US6518432B1/en not_active Expired - Lifetime
- 2000-04-14 AU AU44447/00A patent/AU773962B2/en not_active Ceased
- 2000-04-14 DE DE60029493T patent/DE60029493T2/de not_active Expired - Lifetime
- 2000-04-14 IL IL14558500A patent/IL145585A0/xx active IP Right Grant
-
2001
- 2001-09-24 IL IL145585A patent/IL145585A/en not_active IP Right Cessation
- 2001-10-08 NO NO20014889A patent/NO320810B1/no not_active IP Right Cessation
- 2001-10-11 ZA ZA200108374A patent/ZA200108374B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000063175A2 (en) | 2000-10-26 |
| EP1492769A2 (en) | 2005-01-05 |
| JP2003524625A (ja) | 2003-08-19 |
| AU773962B2 (en) | 2004-06-10 |
| KR20010113799A (ko) | 2001-12-28 |
| BR0009795B1 (pt) | 2011-12-27 |
| CN1370145A (zh) | 2002-09-18 |
| DE60029493T2 (de) | 2007-01-11 |
| NZ514586A (en) | 2003-09-26 |
| ATE333444T1 (de) | 2006-08-15 |
| KR100663811B1 (ko) | 2007-01-03 |
| CA2367410A1 (en) | 2000-10-26 |
| SE9901340D0 (sv) | 1999-04-15 |
| JP4676064B2 (ja) | 2011-04-27 |
| ES2267526T3 (es) | 2007-03-16 |
| CN1138759C (zh) | 2004-02-18 |
| NO20014889D0 (no) | 2001-10-08 |
| IL145585A (en) | 2006-12-31 |
| BR0009795A (pt) | 2002-01-08 |
| US6518432B1 (en) | 2003-02-11 |
| ZA200108374B (en) | 2003-08-06 |
| AU4444700A (en) | 2000-11-02 |
| NO20014889L (no) | 2001-10-08 |
| TWI248433B (en) | 2006-02-01 |
| WO2000063175A3 (en) | 2004-11-11 |
| EP1492769B1 (en) | 2006-07-19 |
| IL145585A0 (en) | 2002-11-10 |
| CA2367410C (en) | 2009-08-11 |
| DE60029493D1 (de) | 2006-08-31 |
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