DK142580B - Fremgangsmaade til fremstilling af piperazinderivater - Google Patents
Fremgangsmaade til fremstilling af piperazinderivater Download PDFInfo
- Publication number
- DK142580B DK142580B DK503071AA DK503071A DK142580B DK 142580 B DK142580 B DK 142580B DK 503071A A DK503071A A DK 503071AA DK 503071 A DK503071 A DK 503071A DK 142580 B DK142580 B DK 142580B
- Authority
- DK
- Denmark
- Prior art keywords
- methylenedioxyphenyl
- piperazine
- propyl
- xylyl
- group
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- 238000002360 preparation method Methods 0.000 title claims description 6
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title claims description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- -1 2-methoxyethoxy Chemical group 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 150000004885 piperazines Chemical class 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical group [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 claims 1
- 150000004645 aluminates Chemical class 0.000 claims 1
- 150000004678 hydrides Chemical class 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- 150000002912 oxalic acid derivatives Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- LOMVENUNSWAXEN-UHFFFAOYSA-N Methyl oxalate Chemical compound COC(=O)C(=O)OC LOMVENUNSWAXEN-UHFFFAOYSA-N 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000006215 cyanomethylation reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- JTHRRMFZHSDGNJ-UHFFFAOYSA-N piperazine-2,3-dione Chemical compound O=C1NCCNC1=O JTHRRMFZHSDGNJ-UHFFFAOYSA-N 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/033—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Description
142580
Patent nr. 14ο 666 angår en fremgangsmåde til fremstilling af N-[l-(3,4-methylendi-oxyphenyl)-propyl-(2)]-Ν'-(α-naphthyl)-piperazin med formlen I' 5 ?2C-°-v. , y_, jf\
I /==\ r^ÆJ
ί3ν_/ i) eller syreadditionssalte heraf, og det ejendommelige 10 ifølge hovedpatentet er, at man omsætter N-(3,4-methy-lendioxyphenyl-propyl-(2))-Ν'-(α-naphthyl)-ethylendi-amin med formlen II' ~°y=\ JC) 2L3 q med oxalsyrediethylester med formlen III*
CoHc0-C-C-0C„Hc o i
20 og derpå reducerer den således fremstillede N—[i— (3,4— methylendioxyphenyl)-propyl-(2)-]-N(α-naphthyl)-pipe-razindion-2,3 med formlen IV
^ >=% ^ /O
H
O O \-f med et metalhydrid og om ønsket overfører den således fremstillede piperazin med den almene formel 11 i et 30 syreadditionssalt heraf.
2 142580
En fremgangsmåde af denne art kan imidlertid anvendes også til fremstilling af andre forbindelser, nemlig sådanne med formlen I (som defineret nedenfor) og opfindelsen angår i overensstemmelse hermed en frem-5 gangsmåde ifølge patent nr. 14o 666 til fremstilling af piperazinderivater med den almene
formel I
/ \
Ar-CH2-CH-N N-/' I
10 CH3 hvori Ar betegner en aromatisk gruppe med to til hinanden annellerede ringe, af hvilke den ring, der ikke er bundet til resten af molekylet, kan være en iso- eller 15 heterocyclisk mættet ring eller en aromatisk ring, fortrinsvis en 3,4-methylen-dioxyphenyl-, indanyl-, tetra- hydronaphthy1-, naphthyl-, 1,4-benzodioxanyl- eller 1 2 chromanylgruppe, og R og R , der kan være ens eller forskellige, betegner hydrogen, halogen, en amino-, 20 acylamino-, nitril- (dvs. -C=N) eller trifluormethyl-gruppe eller en alkyl-, alkoxy-, alkylcarbonyl- eller alkylthiogruppe med 1-4 c-atomer, eller fysiologisk tålelige syreadditionssalte heraf, hvilken fremgangsmåde er ejendommelig ved, at man omsætter et Ν,Ν'-disubsti-25 tueret ethylendiamin-derivat med den almene formel il
Ar-CH,-CH-NH-CH,-CH5-NH-</ ^ 11 ch3 wv 1 2
30 hvori Ar, R og R har den ovenfor anførte betydning, med et oxalsyrederivat med formlen III
ir 111 hvori X betegner halogen eller en lavere alkoxygruppe, 35 og derpå reducerer den således fremstillede piperazin-
2,3-dion med den almene formel IV
5 142580 / \ Γ~·\r1 iv
Ar-CH_-CH-N N-(/ ') iV
H
1 2 5 hvori Ar, R og R har den ovenfor anførte betydning, med et metalhydrid, og, om ønsket, overfører den således fremstillede piperazin med den almene formel I på sædvanlig måde i et fysiologisk tåleligt syreadditionsalt.
Forbindelserne med formlen I er værdifulde læge-10 midler, der navnlig har neuroleptisk virkning.
I forhold til kendte fremgangsmåder til fremstilling af forbindelser af den pågældende type har fremgangsmåden ifølge opfindelsen den fordel, at den anvender meget let tilgængelige udgangsmaterialer. Ethylendi-15 aminderivatet med formlen II kan f.eks. fremstilles i et godt udbytte ved reduktion af den tilsvarende anilin med NaCN i formalinopløsning (cyanometylering) og påfølgende katalytisk hydrering, isolering af den således fremstillede monosubstituerede ethylendlaminforbindelse 20 og omsætning af denne med den tilsvarende keton med formlen Ar-CH2-CO-CH3,(hvori Ar har den ovenfor anførte betydning) under tilstedeværelse af katalytisk aktiveret hydrogen, medens oxalsyrederivatet med formlen III let kan fås ved forestring eller halogenering (f.eks. med 25 SOCl2) af den meget billige oxalsyre. Da såvel syntesen af piperazin-2,3-dionen med formlen IV som dennes reduktion til piperazinen med formlen I forløber glat og med godt udbytte, udgør den nye fremgangsmåde i alt en forenklet syntesevej til opnåelse af piperazinerne med 30 formlen I. Endvidere er det også muligt efter denne fremgangsmåde at fremstille piperaziner med formlen I med sterisk hindring (f.eks. piperaziner/ der i den højre phenylrings orthostilling bærer én substituent) uden vanskeligheder og med godt udbytte.
35 Som syrekomponent i et syreadditionssalt, hvori den fremstillede forbindelse eventuelt overføres, kan f.eks. anvendes saltsyre, hydrogenbromidsyre, svovlsyre, methansulfonsyre, ravsyre og vinsyre.
4 142580
Eksempel 1 a) N-[1-(3,4-methylendioxyphenyl-propyl-(2)]-N1-(o-ethylphenyl)-piperazindion-2,3.
48,9 g, 0,15 mol, N-[o-ethylpheny1]-N'-[3,4-me-5 thylendioxy-a-methyl-phenylethyl]-ethylendiamin og 32,0 g 0,22 mol, oxalsyrediethylester opvarmes under omrøring langsomt i løbet af 1 time til 180°C. Den ved reaktionen fremkomne alkohol destilleres langsomt fra. Efter afsluttet omsætning afkøles og omkrystalliseres først fra 10 tetrachlormethan og derpå fra isopropanol. l-[o-ethyl-phenyl]-4-[3,4-methylendioxy-a-methyl-phenylethyl]-piperazindion-2, 3 har et smeltepunkt på 128-130^0. udbytte: 25,9 g 55% af det teoretiske.
b) N-[1-{3,4-methylendioxyphenyl-propyl-(2)]-N'-(o-15 ethylphenyl)-piperazin, HC1.
19,0 g, 0,05 mol, N-[l-(3,4-methylendioxyphenyl-propyl- (2)]-Ν'-(o-ethyl)-piperazindion-2,3 opløses i 150 ml absolut tetrahydrofuran og dryppes langsomt tinder omrøring til 3,8 g, o,l mol, lithiumaluminiumhydrid i 20 100 ml absolut tetrahydrofuran. Derpå koges i 6 timer under tilbagesvaling. Blandingen henstilles natten over, og overskydende lithiumalanat sønderdeles med vand under afkøling, hvorpå der tilsættes fortyndet saltsyre til stærkt sur reaktion. Den fremkomne krystalgrød suges 25 fra, og der omkrystalliseres fra methanol. N-[1-(3,4-methylendioxyphenyl-propyl-(2)]-N'-(o-ethylphenyl)-piperazin, HC1 har et smeltepunkt på 277°C. Udbytte: 16,0 g, 91% af det teoretiske.
30 Eksempel 2 a) N— £l- (3,4-methylendioxyphenyl-propyl- (2 jJ-N '-(3,4- xylyl)-piperazindion-2,3.
48,9 g, 0,15 mol, N-[1-(3,4-methylendioxyphenyl-propyl- (2) ] -N' - (3,4-xylyl)-ethylendiamin opvarmes sammen 35 med 26,0 g, 0,22 mol, oxalsyredimethylester under omrøring i løbet af 1 time til 180°C. Methanolen, der frigøres, afdestilleres kontinuerligt. Efter afsluttet omsætning omkrystalliseres den afkølede seje olie først
Claims (2)
142580 fra eddikesyreethylester og derpå fra alkohol. N-[l-(3,4-me thylendioxypheny1-propy1-(2)]-N'-(3,4-xyly1)-pi-perazindion-2,3 har et smeltepunkt på 172,5-173,5°C. Udbytte: 29,6 g, 63% af det teoretiske. 5 b) N-[l-(3,4-methylendioxyphenyl-propyl-(2)]-N'- (3,4-xylyl)-piperazindion-2,3 opløses i 200 ml absolut benzen. Under omrøring tildryppes 84 ml, 0,60 hydrid-ækvivalenter, af en benzenisk opløsning af natrium-di-hydro-bis-(2-methoxyethoxy)-aluminat {"SDMA"). Blandin-10 gen omrøres natten over ved stuetemperatur, hvorpå den hydrolyseres ved langsom tildrypning af 60 ml I^O. Den organiske fase fraskilles, og opløsningsmidlet afde-stilleres i vakuum. Til remanensen sættes først methanol og derpå fortyndet saltsyre til kraftig sur reaktion.
15 Krystalgrøden suges fra og omkrystalliseres fra methanol. N- [l~(3,4-methylendioxy- phenyl-propyl-(2)]- Ν'-(3,4-xylyl)-piperazin, HC1 har et smeltepunkt på 252-255°C. Udbytte: 15,3 g, 87% af det teoretiske. 20 Fremgangsmåde ifølge patent nr. 14o 666 til fremstilling af piperazinderivater med den almene formel I 25 *r-CH2-CH hvori Ar betegner en aromatisk gruppe med to til hinan- 30 den annellerede ringe, af hvilke den ring, der ikke er bundet til resten af molekylet, kan være en iso- eller heterocyclisk mættet ring eller en aromatisk ring, for-. trinsvis en 3,4-methylendioxyphenyl-, indanyl-, tetra- hydronaphthyl-,naphthyl-,1,4-benzodioxanyl- eller chrom-1 2 35 anylgruppe, og R og R , der kan være ens eller forskellige, betegner hydrogen, halogen, en amino-, acylamino-, nitril- (dvs. -ON) eller trifluormethylgruppe eller en alkyl-, alkoxy- alkylcarbonyl- eller alkylthiogruppe
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2050684 | 1970-10-15 | ||
| DE19702050684 DE2050684A1 (en) | 1970-10-15 | 1970-10-15 | Neuroleptic 1-aralkyl-4-phenyl-piperazines prodn - by reacting ethylenediamines with oxalic acid derivs,and reducing resulting dioxo |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK142580B true DK142580B (da) | 1980-11-24 |
| DK142580C DK142580C (da) | 1981-07-13 |
Family
ID=5785239
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK503071A DK142580C (da) | 1970-10-15 | 1971-10-15 | Fremgangsmaade til fremstilling af piperazinderivater |
Country Status (12)
| Country | Link |
|---|---|
| AT (1) | AT313902B (da) |
| BG (1) | BG18869A3 (da) |
| CA (1) | CA967159A (da) |
| CH (1) | CH562236A5 (da) |
| DE (1) | DE2050684A1 (da) |
| DK (1) | DK142580C (da) |
| ES (1) | ES395969A1 (da) |
| FI (1) | FI54922C (da) |
| HU (1) | HU162740B (da) |
| PL (1) | PL77016B1 (da) |
| SE (1) | SE395144B (da) |
| YU (1) | YU34695B (da) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2604838A1 (de) * | 1976-02-07 | 1977-08-11 | Knoll Ag | Alkylendioxypiperazinderivate |
-
1970
- 1970-10-15 DE DE19702050684 patent/DE2050684A1/de active Pending
-
1971
- 1971-10-12 CH CH1491871A patent/CH562236A5/xx not_active IP Right Cessation
- 1971-10-12 HU HUBO1323A patent/HU162740B/hu unknown
- 1971-10-13 BG BG18756A patent/BG18869A3/xx unknown
- 1971-10-13 SE SE7112983A patent/SE395144B/xx unknown
- 1971-10-14 PL PL1971151024A patent/PL77016B1/pl unknown
- 1971-10-14 CA CA125,116A patent/CA967159A/en not_active Expired
- 1971-10-14 FI FI2885/71A patent/FI54922C/fi active
- 1971-10-14 ES ES395969A patent/ES395969A1/es not_active Expired
- 1971-10-14 AT AT890171A patent/AT313902B/de not_active IP Right Cessation
- 1971-10-15 YU YU2633/71A patent/YU34695B/xx unknown
- 1971-10-15 DK DK503071A patent/DK142580C/da active
Also Published As
| Publication number | Publication date |
|---|---|
| PL77016B1 (da) | 1975-02-28 |
| HU162740B (da) | 1973-04-28 |
| AT313902B (de) | 1974-03-11 |
| BG18869A3 (da) | 1975-03-20 |
| YU263371A (en) | 1979-07-10 |
| FI54922C (fi) | 1979-04-10 |
| DK142580C (da) | 1981-07-13 |
| DE2050684A1 (en) | 1972-04-20 |
| CA967159A (en) | 1975-05-06 |
| YU34695B (en) | 1979-12-31 |
| ES395969A1 (es) | 1973-12-16 |
| CH562236A5 (da) | 1975-05-30 |
| FI54922B (fi) | 1978-12-29 |
| SE395144B (sv) | 1977-08-01 |
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