FI107605B - Optiskt aktivt alfa-fenyletylamid av 2-[1-(4-t-butylfenyl)-2-pyrrolidon-4-yl]metoxikarbonylbentsoesyra, mellanprodukt och förfarande för framställning av densamma - Google Patents
Optiskt aktivt alfa-fenyletylamid av 2-[1-(4-t-butylfenyl)-2-pyrrolidon-4-yl]metoxikarbonylbentsoesyra, mellanprodukt och förfarande för framställning av densamma Download PDFInfo
- Publication number
- FI107605B FI107605B FI942167A FI942167A FI107605B FI 107605 B FI107605 B FI 107605B FI 942167 A FI942167 A FI 942167A FI 942167 A FI942167 A FI 942167A FI 107605 B FI107605 B FI 107605B
- Authority
- FI
- Finland
- Prior art keywords
- formula
- compound
- optically active
- butylphenyl
- pyrrolidon
- Prior art date
Links
- -1 2- [1- (4-t-butylphenyl) -2-pyrrolidon-4-yl] methoxycarbonylbenzoic acid Chemical compound 0.000 title claims description 36
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 239000000203 mixture Substances 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 11
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000012320 chlorinating reagent Substances 0.000 claims description 6
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical group C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 claims description 3
- FNJSWIPFHMKRAT-UHFFFAOYSA-N Monomethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(O)=O FNJSWIPFHMKRAT-UHFFFAOYSA-N 0.000 claims description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 16
- 238000003786 synthesis reaction Methods 0.000 abstract description 16
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 235000012000 cholesterol Nutrition 0.000 abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 2
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 2
- 239000000194 fatty acid Substances 0.000 abstract description 2
- 229930195729 fatty acid Natural products 0.000 abstract description 2
- 150000004665 fatty acids Chemical class 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- 239000002904 solvent Substances 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 150000007514 bases Chemical class 0.000 description 14
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 238000000921 elemental analysis Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- JMVIVASFFKKFQK-UHFFFAOYSA-N 1-phenylpyrrolidin-2-one Chemical class O=C1CCCN1C1=CC=CC=C1 JMVIVASFFKKFQK-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000001819 mass spectrum Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- ZPWDKFLAMVCCET-UHFFFAOYSA-N 4-[1-(4-tert-butylphenyl)-5-oxopyrrolidin-3-yl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(C2CC(=O)N(C2)C=2C=CC(=CC=2)C(C)(C)C)=C1 ZPWDKFLAMVCCET-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IFSJQWXZIHWZQG-LBPRGKRZSA-N C1(=CC=CC=C1)[C@H](C)NC(C1=C(C=CC=C1)C(=O)OC)=O Chemical compound C1(=CC=CC=C1)[C@H](C)NC(C1=C(C=CC=C1)C(=O)OC)=O IFSJQWXZIHWZQG-LBPRGKRZSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QEZGRWSAUJTDEZ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(piperidine-1-carbonyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)C(=O)N1CCCCC1 QEZGRWSAUJTDEZ-UHFFFAOYSA-N 0.000 description 1
- ZPWDKFLAMVCCET-HNNXBMFYSA-N 4-[(3R)-1-(4-tert-butylphenyl)-5-oxopyrrolidin-3-yl]-2-methoxybenzoic acid Chemical compound C(C)(C)(C)C1=CC=C(C=C1)N1C(C[C@@H](C1)C1=CC(=C(C(=O)O)C=C1)OC)=O ZPWDKFLAMVCCET-HNNXBMFYSA-N 0.000 description 1
- IMYGMSWPECINMA-AWEZNQCLSA-N C(C)(C)(C)C1=CC=C(C=C1)N1C(C[C@@H](C1)C1=C(C(=O)O)C=CC=C1C(=O)OC)=O Chemical compound C(C)(C)(C)C1=CC=C(C=C1)N1C(C[C@@H](C1)C1=C(C(=O)O)C=CC=C1C(=O)OC)=O IMYGMSWPECINMA-AWEZNQCLSA-N 0.000 description 1
- 241000289659 Erinaceidae Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004136 fatty acid synthesis Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- CXBRSNZDFNQVGQ-IRLDBZIGSA-N methyl 2-[(3R)-1-(4-tert-butylphenyl)-5-oxopyrrolidin-3-yl]-3-[[(1R)-1-phenylethyl]carbamoyl]benzoate Chemical compound C1(=CC=CC=C1)[C@@H](C)NC(C1=C(C(=CC=C1)C(=O)OC)[C@H]1CC(N(C1)C1=CC=C(C=C1)C(C)(C)C)=O)=O CXBRSNZDFNQVGQ-IRLDBZIGSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (4)
1. Diastereomer av α-fenyletylamid av 2-[l-(4-t-butylfenyl)-2-pyrrolidon-4-yl]- metoxikarbonylbensoesyra med formeln (I-b') 4 \-/ ^ (I-b') o O^R väri 4-positionen i pyrrolidonringen har S-konfiguration och väri R är en optiskt ak-: tiv gmpp med formeln ''i _γΉΟ
10. H \=/ • · · • · ♦
2. Diastereomer enligt patentkrav 1, kännetecknad av att den är (S)-a-fenyl- etylamid av (-)-2-[(S)-l-(4-t-bntylfenyl)-2-pyrrolidon-4-yl]metoxikarbonylbensoe- .···. syra.
• · · ··· 3. Förfarande för framställning av en diastereomer av α-fenyletylamid av 2-[l-(4- ··· · . * * *; 15 t-butylfenyl)-2-pyrrolidon-4-yl]metoxikarbonylbensoesyra med formeln (I-b') • · · • · « ♦ • · · « • · 107605 4/~V/S ^ w X^'°VJVJ 0 O^R van 4-positionen i pyrrolidonringen har S-konfigura1ion och väri R är en optiskt ak-tiv grapp med formeln -rrO H H \---/ 5 kännetecknat av att förfarandet omfattar stegen: i) omsättning av en förening med formeln (I-a) i form av en racemisk blandning -ηΓΛ-Λ ri \-/ (I-a) O • · · • · ... . med ett kloreringsmedel for överföring av foreningen tili motsvarande syraklorid, • · · • · ii) omsättning av den i steg i) framställda syrakloriden med en optiskt aktiv a- : T: 10 fenyletylamin med formeln (IV) r „-Π/Λ "! nh2 \==/ • · · • » · · ·1...: varvid man erhäller en diastereomerblandning av en förening med formeln (I-b) • · • · « ♦ · 107605 -f/’vS \ / (Ib) o O^R van R har ovan angiven betydelse, och iii) utforing av uppdelning av den i steg ii) erhällna diastereomerblandningen, varvid man erhäller en optiskt aktiv forening med fonneln (I-b'). 5 4. 2-[l-(4-t-butylfenyl)-2-pyrrolidon-4-yl]metoxikarbonylbensoesyra med for- meln (I-a) i form av en racemisk blandning 4/λ/ί \ J (I-a) O OH • ·· • · · • ♦ · ··· ♦ · • · • · · • · · ♦ · ♦ ·· • * ♦ · ♦ · · • · · • « · ♦ ♦ ♦ ··· « · ··· • · · • · · · • · · • « • « • · · ·♦ • · » ·« ♦ ·
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24288792 | 1992-09-11 | ||
| JP24288792 | 1992-09-11 | ||
| JP9301274 | 1993-09-08 | ||
| PCT/JP1993/001274 WO1994006767A1 (en) | 1992-09-11 | 1993-09-08 | Optically active 1-phenylpyrrolidone derivative, intermediate for producing the same, and process for producing both |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI942167A0 FI942167A0 (sv) | 1994-05-10 |
| FI942167L FI942167L (sv) | 1994-07-08 |
| FI107605B true FI107605B (sv) | 2001-09-14 |
Family
ID=17095708
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI942167A FI107605B (sv) | 1992-09-11 | 1994-05-10 | Optiskt aktivt alfa-fenyletylamid av 2-[1-(4-t-butylfenyl)-2-pyrrolidon-4-yl]metoxikarbonylbentsoesyra, mellanprodukt och förfarande för framställning av densamma |
| FI20001893A FI108130B (sv) | 1992-09-11 | 2000-08-28 | Förfarande för framställning av farmaceutiskt aktiv (S)-(+)-4-[1-(4-t-butylfenyl)-2-pyrrolidon-4-yl]metoxibensoesyra eller en ester därav |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI20001893A FI108130B (sv) | 1992-09-11 | 2000-08-28 | Förfarande för framställning av farmaceutiskt aktiv (S)-(+)-4-[1-(4-t-butylfenyl)-2-pyrrolidon-4-yl]metoxibensoesyra eller en ester därav |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US5475118A (sv) |
| EP (2) | EP0916657B9 (sv) |
| JP (1) | JP2724634B2 (sv) |
| KR (1) | KR0141657B1 (sv) |
| AT (2) | ATE186907T1 (sv) |
| AU (1) | AU663233B2 (sv) |
| CA (1) | CA2122705C (sv) |
| DE (2) | DE69327092T2 (sv) |
| DK (1) | DK0627419T3 (sv) |
| ES (2) | ES2139670T3 (sv) |
| FI (2) | FI107605B (sv) |
| HU (1) | HU215598B (sv) |
| NO (1) | NO300130B1 (sv) |
| WO (1) | WO1994006767A1 (sv) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999043318A1 (fr) * | 1998-02-24 | 1999-09-02 | Taiho Pharmaceutical Co., Ltd. | AGENTS DE REDUCTION DU TAUX DE Lp(a) ET INHIBITEURS DE LA PRODUCTION D'APOPROTEINE (a) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0393607T3 (da) * | 1989-04-19 | 1996-03-18 | Otsuka Pharma Co Ltd | Phenylcarboxylsyrederivater med en heteroring |
| JPH06192221A (ja) * | 1992-12-25 | 1994-07-12 | Taiho Yakuhin Kogyo Kk | 光学活性な１−（４−ｔ−ブチルフェニル）−５−オキソ−３−ピロリジンカルボン酸の製造方法 |
-
1993
- 1993-09-08 EP EP98203959A patent/EP0916657B9/en not_active Expired - Lifetime
- 1993-09-08 JP JP6507962A patent/JP2724634B2/ja not_active Expired - Lifetime
- 1993-09-08 EP EP93919628A patent/EP0627419B1/en not_active Expired - Lifetime
- 1993-09-08 WO PCT/JP1993/001274 patent/WO1994006767A1/ja active IP Right Grant
- 1993-09-08 ES ES93919628T patent/ES2139670T3/es not_active Expired - Lifetime
- 1993-09-08 ES ES98203959T patent/ES2247657T3/es not_active Expired - Lifetime
- 1993-09-08 AU AU49832/93A patent/AU663233B2/en not_active Ceased
- 1993-09-08 KR KR1019940701558A patent/KR0141657B1/ko not_active Expired - Fee Related
- 1993-09-08 AT AT93919628T patent/ATE186907T1/de not_active IP Right Cessation
- 1993-09-08 AT AT98203959T patent/ATE309212T1/de not_active IP Right Cessation
- 1993-09-08 US US08/211,950 patent/US5475118A/en not_active Expired - Fee Related
- 1993-09-08 DE DE69327092T patent/DE69327092T2/de not_active Expired - Fee Related
- 1993-09-08 CA CA002122705A patent/CA2122705C/en not_active Expired - Fee Related
- 1993-09-08 HU HU9401470A patent/HU215598B/hu not_active IP Right Cessation
- 1993-09-08 DK DK93919628T patent/DK0627419T3/da active
- 1993-09-08 DE DE69333903T patent/DE69333903T2/de not_active Expired - Fee Related
-
1994
- 1994-05-10 NO NO941757A patent/NO300130B1/no unknown
- 1994-05-10 FI FI942167A patent/FI107605B/sv active
-
2000
- 2000-08-28 FI FI20001893A patent/FI108130B/sv active
Also Published As
| Publication number | Publication date |
|---|---|
| FI108130B (sv) | 2001-11-30 |
| CA2122705C (en) | 1997-11-18 |
| FI20001893L (sv) | 2000-08-28 |
| ES2247657T3 (es) | 2006-03-01 |
| EP0627419B1 (en) | 1999-11-24 |
| AU663233B2 (en) | 1995-09-28 |
| DE69333903D1 (de) | 2005-12-15 |
| NO941757D0 (no) | 1994-05-10 |
| NO300130B1 (no) | 1997-04-14 |
| FI942167A0 (sv) | 1994-05-10 |
| WO1994006767A1 (en) | 1994-03-31 |
| ATE186907T1 (de) | 1999-12-15 |
| DK0627419T3 (da) | 2000-04-25 |
| JP2724634B2 (ja) | 1998-03-09 |
| HUT70219A (en) | 1995-09-28 |
| DE69327092D1 (de) | 1999-12-30 |
| EP0916657B9 (en) | 2006-05-17 |
| ES2139670T3 (es) | 2000-02-16 |
| HU9401470D0 (en) | 1994-08-29 |
| CA2122705A1 (en) | 1994-03-31 |
| DE69327092T2 (de) | 2000-05-25 |
| NO941757L (no) | 1994-05-10 |
| EP0916657A1 (en) | 1999-05-19 |
| FI942167L (sv) | 1994-07-08 |
| ATE309212T1 (de) | 2005-11-15 |
| US5475118A (en) | 1995-12-12 |
| KR0141657B1 (ko) | 1998-06-01 |
| HU215598B (hu) | 1999-01-28 |
| EP0627419A4 (en) | 1995-02-08 |
| EP0627419A1 (en) | 1994-12-07 |
| DE69333903T2 (de) | 2006-07-27 |
| AU4983293A (en) | 1994-04-12 |
| EP0916657B1 (en) | 2005-11-09 |
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