NO823596L - Fremgangsmaate for fremstilling av 4-(3-metyl-2-butenyl)-1,2-difenyl-3,5-dioksopyrazolidin - Google Patents
Fremgangsmaate for fremstilling av 4-(3-metyl-2-butenyl)-1,2-difenyl-3,5-dioksopyrazolidinInfo
- Publication number
- NO823596L NO823596L NO823596A NO823596A NO823596L NO 823596 L NO823596 L NO 823596L NO 823596 A NO823596 A NO 823596A NO 823596 A NO823596 A NO 823596A NO 823596 L NO823596 L NO 823596L
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- diphenyl
- butenyl
- dioxopyrazolidine
- palladium
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 15
- RBBWCVQDXDFISW-UHFFFAOYSA-N Feprazone Chemical compound O=C1C(CC=C(C)C)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 RBBWCVQDXDFISW-UHFFFAOYSA-N 0.000 title claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
- XDPKQGKEOCYMQC-UHFFFAOYSA-N 1,2-diphenylpyrazolidine-3,5-dione Chemical compound O=C1CC(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 XDPKQGKEOCYMQC-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- XXIKYCPRDXIMQM-UHFFFAOYSA-N Isopentenyl acetate Chemical compound CC(C)=CCOC(C)=O XXIKYCPRDXIMQM-UHFFFAOYSA-N 0.000 claims description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- -1 alkali metal salt Chemical class 0.000 claims description 5
- 229910003002 lithium salt Inorganic materials 0.000 claims description 5
- 159000000002 lithium salts Chemical class 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 229960000489 feprazone Drugs 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- UAXNXOMKCGKNCI-UHFFFAOYSA-N 1-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 UAXNXOMKCGKNCI-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 150000002940 palladium Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- JKXQKGNGJVZKFA-UHFFFAOYSA-N 1-chloro-3-methylbut-2-ene Chemical compound CC(C)=CCCl JKXQKGNGJVZKFA-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000011707 mineral 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
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/28—Two oxygen or sulfur atoms
- C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
- C07D231/32—Oxygen atoms
- C07D231/34—Oxygen atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Denne oppfinnelse angår en ny fremgangsmåte for fremstilling av 4-(3-metyl-2-butenyl)-1,2-difenyl-3,5-diokso-pyrazolidin.
Britisk patent 1.301.857 - beskriver to derivater av 1,2-difenyl-3,5-dioksopyrazolidin og fremgangsmåter for fremstilling derav. ■Et av disse to derivater er 4-(3-metyl-2-butenyl)-1,2-difeny1-3,5-dioksopyrazolidin, feprazon, et verdifullt smertestillende og antiinflammatorisk middel som for tiden anvendes ved behandling av reumatiske og artrittiske
■lidelser og generelt véd behandling av inflammatoriske lidelser.
Blant'.de • metoder som finnes for fremstilling av denne forbindelse, er beskrevet omsetningen av 1,2-difenyl-3,5-diokso-pyrazolidin eller et av dens alkalisalter med et halogenid,
dvs. 3-metyl-2-butenyl-klorid eller -bromid.
Denne omsetning omfatter en nukleofil fortrengning mellom anionet av 1,2-difenyl-3,5-dioksopyrazolidin, som har en aktiv metylengruppe,• og det aktive'allylhalogenid, f.eks. 3-metyl-2-buteriylklorid,
Formålet med foreliggende oppfinnelse er å tilveiebringe en ny fremgangsmåte for fremstilling av 4—(3-metyl-2-butenyl)-1,2-difenyl-3,5-dioksopyrazolidin, og fremgangsmåten karakteriseres ved at 3-metyl-2-butenyl-acetat omsettes med et alkalimetallsalt av 1,2-difenyl-3,5-dioksopyrazolidin i nærvær av palladiumkomplekser som katalysatorer,.! henhold
. til følgende skjema:
En av.hovedfbrdelene ved oppfinnelsen som beskrevet oven-for, er at 3-metyl-2-butenyl-acetat, i motsetning til 3-metyl-2-butenyl-halogénidene, er et stabilt og håndterbart stoff: Det kan fremstilles fra isopren, eddiksyre og eddiksyreånhydrid i nærvær av en passende katalysator, i henhold til belgisk .patent 640.309. André fordeler som oppnås i henhold til opp-" finnelsen, er selektiviteten av C- i forhold til 0-alkyler.ing, og minimalisering av eliminasjonsreaksjonen.
Mer spesielt omfatter fremgangsmåten ifølge oppfinnelsen omsetning av 3-mety'l-2-buteny 1-acetat med et alkalisalt,
,så som natrium-, kalium- eller litiumsalter, hensiktsmessig litiumsaltet, av 1,2-difenyl-3,5-dioksopyrazolidin i nærvær av palladiumkomplekser som katalysatorer. Foretrukne katalysatorer er tetrakis (trifenylfosfin)palladium (0) [(Ph-^P)^Pd] , bis-(dibenzyliden-aceton)palladium (0) [ (dba)2Pd^1 og
bis-[bis- (1,2-difenylfosfinoetan) Ipalladium (0)' [ (DIPH0S2)Pd (o}] , hensiktsmessig tetrakis-(trifenylfosfin)-palladium (0) i nærvær av slike ligander som trif enylfosf in (TPP) 1, 2-(bis-dif eny 1-fosfinoetan) (DIPHOS), heksametylfosfortriamid (HMP), fortrinns-, vis trifenylfosfin. Oppløsningsmidler som fortrinnsvis anvendes ved omsetningen, er eter-oppløsningsmidler så som tetrahydrofuran, .1, 2-dimetoks.yetan og dimetylsulf oksyd , særlig tetrahydrofuran under vannfrie betingelser.
Omsetningen foretas vanligvis, ved at 3-metyl-2-butenyl-acetat oppløst i det passende oppløsningsmiddel, f. eks. tetrahydrofuran,. blandes ved romtemperatur med palladiumkomplekset og den passende ligand. Tilfredsstillende mengder av
katalysator varierer fra 0,1 til 10 mol?.. ■ Oppløsningen av alkalimetallsaltet av 1,2-difenyl-3,5-dioksopyrazolidin
(2 til 4 mol) • tilsettes derefter raskt, og blandingen omrøres ved en temperatur fra romtemperatur til ?0°C. Derefter helles
reaksjonsblandingen.i surt vann (pH 4 til 5), ekstraheres med et egnet oppløsningsmiddel, f.eks. etylacetat, etyleter eller diklor-metan. Produktet oppnådd eftef avdampning av opp-løsningsmidlet renses direkte ved kolonnekromatografi eller ved reekstraksjon med et basisk, vandig medium. I sistnevnte tilfelle isoleres produktet efter surgjøring med en mineralsyre, fortrinnsvis saltsyre, og ekstraksjon med et passende oppløsnings-middel. Ytterligere rensning oppnås' ved kolonnekromatografi.
De følgende eksempler skal tjene til å illustrere oppfinnelsen ytterligere: E ksempel 1
3-metyl-2-buteny1-acetat (5 g, 0,039 mol),. trifenylfosfin (0,93 g) og tetrakis-(trifenylfosfin)-palladium (0) (1,42 g, 0,00123.mol) i 75 ml tørr tetrahydrofuran ble omrørt i
15 minutter ved romtemperatur. En oppløsning av litiumsaltet
av 1,2-difenyl-3,5-dioksopyrazolidin (20,13 g, 0,078 mol) opp-løst i 200 ml vannfri tetrahydrofuran ble derefter tilsatt.alt på en gang, og den resulterende blanding ble tilbakeløps-behandlet i 15 timer under nitrogen. Reaksjonsoppløsningen ble konsentrert og derefter hellet i overskudd av vann. Efter sur-' gjøring til pH 4-5 ble den vandige oppløsning ekstrahert med metylenklorid. Det organiske lag ble fraskilt, tørret (MgSO^) og inndampet til tørrhet for å gi tittelforbindelsen som råprodukt. Rensning ved kolonnekromatografi (silikagel)
(CH^jC^/CH^CN 98:2 volum/volum) ga den ønskede forbindelse i ren form, sm.p. 15 6°C.
Analyse for C2oH20N2C2:
Beregnet: % C 74,79, H 6,29, N 8,74
Funnet: % C 75,14, H 6,37, N 8,68.
Eksempel 2
3-metyl-2-butény1-acetat (5'g, 0,039 mol), 1-2-(bis-difenylfosfinoetan) (0,155 g, 0,39 mmol) og bis-(dibenzylidenaceton)-palladium (0) (0,3 g, 0,522 mmol) i 75 ml vannfri tetrahydrofuran ble omrørt i 10 minutter ved romtemperatur. En oppløsning
av .litiumsaltet av 1,2-difenyl-3,5-dioksopyrazolldin (20,13 g, 0,078 mol') i 150 ml vannfri .tetrahydrofuran ble derefter-tilsatt alt på en gang, og den resulterende blanding ble omrørt i 48 timer ved romtemperatur. Ved derefter å gå frem som beskrevet i eksempel 1, fikk man den ønskede forbindelse, sm.p. 156°C. Analyse for C2o<H>20<*S,>2°2<:>
Beregnet: I c 74, 97, I! 6,29, N 8,74
Funnet: % C 74,85, H 6,11, N- 8,81
Claims (9)
1. Fremgangsmåte for fremstilling- av 4-(3-metyl-2-butenyi)-1,2-difenyl-3,5-dioksopyrazolidin med formelen
karakterisert ved at 3-metyl-2-buteny1-acetat
omsettes med et alkalimetallsalt av 1;2-difenyl-3,5-dickso-pyrazolidin i nærvær av en egnet katalysator og av en ligand.
2 i Fremgangsmåte ifølge krav 1, karakterisert
■ved at natrium-, kalium- eller litiumsaltet av 1,2-difenyl-3 ,5-dioksopyrazolidin anvendes-.
3. Fremgangsmåte ifølge krav 1 og 2, karakterisert ved at det. som katalysator anvendes; et palladiumkompleks...
4. Fremgangsmåte ifølge krav 3, karakterisert ved at det som palladiumkompleks anvendes tetrakis-(trifenylfosfiri)palladium (0), bis-(dibenzylidenaceton)-
palladium - (0) eller, bis-[bis-(1,2-difenylfosfinoetan]-palladium (0).
5. Fremgangsmåte ifølge krav 1 til'4,
. karakterisert ved at det som ligand anvendes
trifenylfosfin, 1,2 - (bis-difenylfosfinoetan) eller heksametylfosfortriamid..
6. Fremgangsmåte ifølge krav 1 til- 5, karakterisert ved at omsetningen utføres i nærvær av et inert, organisk oppløsningsmiddel.
7. Fremgangsmåte ifølge krav 6, karakteriser, t ved at det som inert organisk oppløsningsmiddel anvendes tetrahydrofuran, 1,2-dimetoksyetan eller dimetylsulfoksyd.
8..-Fremgangsmåte ifølge krav 1 til 7', karakterisert ved at omsetningen utføres ved en temperatur fra 20 til 70°C.
9. " Anvendelse, av 3-metyl-2-butenyl-acetat ved fremstilling av feprazon.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT24772/81A IT1168184B (it) | 1981-10-29 | 1981-10-29 | Processo per la preparazione della 4-(3-metil-2-butanile)-1,2-difenil-3,5 dichetopirazolidina |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO823596L true NO823596L (no) | 1983-05-02 |
Family
ID=11214682
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO823596A NO823596L (no) | 1981-10-29 | 1982-10-28 | Fremgangsmaate for fremstilling av 4-(3-metyl-2-butenyl)-1,2-difenyl-3,5-dioksopyrazolidin |
Country Status (19)
| Country | Link |
|---|---|
| JP (1) | JPS5888365A (no) |
| KR (1) | KR840001955A (no) |
| AR (1) | AR231832A1 (no) |
| AT (1) | AT379151B (no) |
| CA (1) | CA1179354A (no) |
| CH (1) | CH651555A5 (no) |
| DK (1) | DK477882A (no) |
| ES (1) | ES516902A0 (no) |
| FI (1) | FI823545L (no) |
| FR (1) | FR2515646B1 (no) |
| GB (1) | GB2108125B (no) |
| GR (1) | GR77724B (no) |
| IT (1) | IT1168184B (no) |
| NL (1) | NL8204170A (no) |
| NO (1) | NO823596L (no) |
| PH (1) | PH19644A (no) |
| PT (1) | PT75755B (no) |
| SE (1) | SE8206143L (no) |
| YU (1) | YU240282A (no) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107778247A (zh) * | 2016-08-30 | 2018-03-09 | 天津太平洋制药有限公司 | 一种非普拉宗及其中间体的制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1301857A (no) * | 1969-06-27 | 1973-01-04 |
-
1981
- 1981-10-29 IT IT24772/81A patent/IT1168184B/it active
-
1982
- 1982-10-07 AT AT0370382A patent/AT379151B/de not_active IP Right Cessation
- 1982-10-14 PH PH27984A patent/PH19644A/en unknown
- 1982-10-18 FI FI823545A patent/FI823545L/fi not_active Application Discontinuation
- 1982-10-26 GR GR69645A patent/GR77724B/el unknown
- 1982-10-26 YU YU02402/82A patent/YU240282A/xx unknown
- 1982-10-26 CH CH6249/82A patent/CH651555A5/de not_active IP Right Cessation
- 1982-10-27 PT PT75755A patent/PT75755B/pt unknown
- 1982-10-28 DK DK477882A patent/DK477882A/da not_active Application Discontinuation
- 1982-10-28 JP JP57189954A patent/JPS5888365A/ja active Pending
- 1982-10-28 NL NL8204170A patent/NL8204170A/nl not_active Application Discontinuation
- 1982-10-28 GB GB08230767A patent/GB2108125B/en not_active Expired
- 1982-10-28 SE SE8206143A patent/SE8206143L/xx not_active Application Discontinuation
- 1982-10-28 NO NO823596A patent/NO823596L/no unknown
- 1982-10-28 CA CA000414428A patent/CA1179354A/en not_active Expired
- 1982-10-28 KR KR1019820004867A patent/KR840001955A/ko unknown
- 1982-10-28 ES ES516902A patent/ES516902A0/es active Granted
- 1982-10-29 FR FR8218200A patent/FR2515646B1/fr not_active Expired
- 1982-10-29 AR AR291152A patent/AR231832A1/es active
Also Published As
| Publication number | Publication date |
|---|---|
| ATA370382A (de) | 1985-04-15 |
| CA1179354A (en) | 1984-12-11 |
| SE8206143L (sv) | 1983-04-30 |
| AR231832A1 (es) | 1985-03-29 |
| PT75755B (en) | 1985-11-20 |
| FI823545A0 (fi) | 1982-10-18 |
| JPS5888365A (ja) | 1983-05-26 |
| NL8204170A (nl) | 1983-05-16 |
| ES8308855A1 (es) | 1983-10-01 |
| CH651555A5 (de) | 1985-09-30 |
| GB2108125B (en) | 1985-03-20 |
| FR2515646B1 (fr) | 1986-02-14 |
| ES516902A0 (es) | 1983-10-01 |
| GB2108125A (en) | 1983-05-11 |
| YU240282A (en) | 1985-03-20 |
| AT379151B (de) | 1985-11-25 |
| FR2515646A1 (fr) | 1983-05-06 |
| FI823545L (fi) | 1983-04-30 |
| IT8124772A0 (it) | 1981-10-29 |
| KR840001955A (ko) | 1984-06-07 |
| DK477882A (da) | 1983-04-30 |
| PH19644A (en) | 1986-06-04 |
| SE8206143D0 (sv) | 1982-10-28 |
| PT75755A (en) | 1982-11-01 |
| IT1168184B (it) | 1987-05-20 |
| GR77724B (no) | 1984-09-25 |
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