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DE1670360A1 - Process for the preparation of derivatives of piperazine - Google Patents

Process for the preparation of derivatives of piperazine

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Publication number
DE1670360A1
DE1670360A1 DE19661670360 DE1670360A DE1670360A1 DE 1670360 A1 DE1670360 A1 DE 1670360A1 DE 19661670360 DE19661670360 DE 19661670360 DE 1670360 A DE1670360 A DE 1670360A DE 1670360 A1 DE1670360 A1 DE 1670360A1
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DE
Germany
Prior art keywords
piperazine
general formula
acid
hcl
carbon atoms
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
DE19661670360
Other languages
German (de)
Inventor
Stachel Dr Adolf
Resag Dr Klaus
Nitz Dr Rolf-Eberhard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cassella Farbwerke Mainkur AG
Original Assignee
Cassella Farbwerke Mainkur AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cassella Farbwerke Mainkur AG filed Critical Cassella Farbwerke Mainkur AG
Publication of DE1670360A1 publication Critical patent/DE1670360A1/en
Pending legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic 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
    • C07D295/04Heterocyclic 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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08Heterocyclic 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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084Heterocyclic 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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088Heterocyclic 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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

CASSELLA FARBWERKE MAINKUR Ref · Nr* 2769 /CASSELLA FARBWERKE Mainkur Ref · No * 2769 / AKTIENGESELLSCHAFTSHARED COMPANY

FRANKFURT(MAIN)-FECHENHEIm 6 Frankfurt/M-Fechenheim, den 29.6.66FRANKFURT (MAIN) -FECHENHEIm 6 Frankfurt / M-Fechenheim, June 29th, 1966

Dr. Rdm/Wa.Dr. Rdm / Wa.

Verfahren zur Herstellung von Derivaten des Piperazins. Process for the preparation of derivatives of piperazine .

Die Erfindung betrifft ein Verfahren zur Herstellung von Piperazinderivaten der allgemeinen FormelThe invention relates to a process for the preparation of piperazine derivatives of the general formula

ROA /V-A,- N N - A„ - OOe—<ROA / V-A, - N N - A "- OOe - <

0
RO R1
0
RO R 1

in der R einen Alkylrest mit 1 oder 2 C-Atomen, R. Wasserstoff oder einen Alkoxyrest mit 1 oder 2 C-Atomen und A.. und A_in which R is an alkyl radical with 1 or 2 carbon atoms, R. is hydrogen or an alkoxy radical with 1 or 2 carbon atoms and A .. and A_

gerad- oder verzweigkettige Alkylenrest mit 1 bis 4 C-Atomen bedeuten.straight or branched chain alkylene radical with 1 to 4 carbon atoms mean.

Das erfxndungsgemässe Verfahren ist dadurch gekennzeichnet, daß man nach an sich bekannten Methoden entwederThe method according to the invention is characterized in that either by methods known per se

a) eine Trialkoxybenzoesäure der allgemeinen Formela) a trialkoxybenzoic acid of the general formula

HOOCHOOC

bzw. deren funktionelIe Derivate mit einem Alkohol der allgemeinen Formelor their functional derivatives with an alcohol general formula

/—v/ —V

- A- - OH- A- - OH

gegebenenfalls in Anwesenheit eines säurebindenden Mittels umsetzt, oder daß man optionally reacted in the presence of an acid-binding agent, or that one

009844/1898 " 2 "009844/1898 " 2 "

BAD ORIGINALBATH ORIGINAL

- 2 - Ref. 2769- 2 - Ref. 2769

b) einen Trialkoxybenzoesäurehalogenalkylester der allgemeinen Formelb) a trialkoxybenzoic acid haloalkyl ester of the general formula

RORO

RO^ \ COO-A2 -Hai,RO ^ \ COO-A 2 -Shark,

RORO

in der Hai ein Halogenatom ist, mit einem Piperazinderivat der allgemeinen Formelin which Hai is a halogen atom with a piperazine derivative the general formula

K, - N N K, - NN

gegebenenfalls in Anwesenheit eines säurebindenden Mittels kondensiert, oder daß manoptionally condensed in the presence of an acid-binding agent, or that one

c) ein Alkalisalz einer Trialkoxybenzoesäure der allgemeinen Formelc) an alkali salt of a trialkoxybenzoic acid of general formula

HOOC mit einem Piperazinderivat der allgemeinen FormelHOOC with a piperazine derivative of the general formula

umsetzt.implements.

Die Salze der erhaltenen Piperazinderivate sind farblose, kristalline, in Wasser leicht lösliche Substanzen. Sie stellen wertvolle Arzneimittel dar. Insbesondere sind sie ausgezeichnete Coronardilatatoren und in dieser Hinsicht bekannten Stoffen dieser Art überlegen.The salts of the piperazine derivatives obtained are colorless, crystalline substances easily soluble in water. They are valuable medicines. In particular, they are excellent coronary dilators and in that regard superior to known substances of this type.

009844/1898009844/1898

- 3 - Ref. 2769- 3 - Ref. 2769

Beispiel 1: Example 1 :

1-(2',3',4'-Trimethoxyphenyl-isopropyl)-4-(3"f4",5"-trimethoxybenzoyl-ß-oxypropyl) -piper azin-dihydrochlor id.1- (2 ', 3', 4'-trimethoxyphenyl-isopropyl) -4- (3 " f 4", 5 "-trimethoxybenzoyl-β-oxypropyl) -piper azine dihydrochloride.

17,6 g (= 0.05 Mol) l-(2',3*,4'-Trimethoxyphenyl-isopropyl)-4-(ß-^xypropyl)-piperazin werden in 100 ecm wasserfreiem benzol gelöst und bei Zimmertemperatur innerhalb 30 Minuten eine Lösung von 11,5 g (= 0.O5 Mol) 3,4,5-Trimethoxybenzoylchlorid in 50 ecm trockenem Benzol zugetropft. Dann rührt man 5-6 Stunden unter Kochen am Rückfluss. Nach Erkalten versetzt man das Reaktionsgemisch mit 200 ecm Wasser, rührt 1 Stunde bei Zimmertemperatur und trennt die wässerige Schicht vom Benzol ab. Diese stellt man mit wässerigem 10-proz. Ammoniak alkalisch und nimmt das abgeschiedene Öl in Äther auf. Die Ätherlösung wäscht man dreimal mit Wasser und trocknet sie über geglühtem Natriumsulfat. Nun destilliert man das Lösungsmittel ab, nimmt das zurückbleibende farblose, zähe Öl in wenig wasserfreiem Alkohol auf und versetzt mit alkoholischer Salzsäure bis zur kongosauren Reaktion. Nach Stehen unter Eiskühlung saugt man das Kristallisat ab. Aus wasserfreiem Alkohol umkristallisiert, erhält man so das l-(2· ,3· ^'-Trimethoxyphenyl-isopropyD^-O11^",^"-trimethoxybenzoyl-ß-oxypropyl)-piperazin-dihydrochlorid in farblosen Kristallen vom Fp 205°. Ausbeute: 22 g = 71 % der Theorie.17.6 g (= 0.05 mol) l- (2 ', 3 *, 4'-trimethoxyphenyl-isopropyl) -4- (ß- ^ xypropyl) -piperazine are dissolved in 100 ecm anhydrous benzene and at room temperature within 30 minutes A solution of 11.5 g (= 0.O5 mol) of 3,4,5-trimethoxybenzoyl chloride in 50 ecm of dry benzene was added dropwise. The mixture is then stirred under reflux for 5-6 hours. After cooling, the reaction mixture is mixed with 200 ecm of water, stirred for 1 hour at room temperature and the aqueous layer is separated off from the benzene. This is made with aqueous 10 percent. Ammonia is alkaline and absorbs the separated oil in ether. The ethereal solution is washed three times with water and dried over calcined sodium sulfate. The solvent is then distilled off, the remaining colorless, viscous oil is taken up in a little anhydrous alcohol and alcoholic hydrochloric acid is added until the Congo acidic reaction occurs. After standing while cooling with ice, the crystals are filtered off with suction. Recrystallized from anhydrous alcohol, l- (2 ·, 3 · ^ '- trimethoxyphenylisopropyD ^ -O 11 ^ ", ^" - trimethoxybenzoyl-β-oxypropyl) piperazine dihydrochloride is obtained in colorless crystals with a melting point of 205 ° . Yield: 22 g = 71 % of theory.

Beispiel 2sExample 2s

l-(3· ,4f-Dimethoxybenzyl)-4-(3",4",5"-trimethoxybenzoyl-^~- oxypropyl)-pxperazin-dihydrochlorid. 1- (3 ·, 4 f -dimethoxybenzyl) -4- (3 ", 4", 5 "-trimethoxybenzoyl- ^ ~ - oxypropyl) -pxperazine dihydrochloride.

23,6 g {- 0.1 Mol) 3,4-Dimethoxybenzyl-piperazin werden in23.6 g {- 0.1 mol) 3,4-dimethoxybenzyl-piperazine are in

Q098U/1898 _ 4 _Q098U / 1898 _ 4 _

. -."Vi BADORiGINAL. -. "Vi BADORiGINAL

100 ecm Dimethylformamid gelöst und nach Zusatz von 5,4 g (=0.1 Mol) Natriummethylat bei 50-60° unter Rühren eine Lösung von 29 g (= 0.1 Mol) 3,4,5-Trimethoxybenzoesäure-^- chlorpropylester in 50 ecm Dimethylformamid innerhalb 1 Stunde zugetropft. Dann rührt man 12 Stunden bei 100°. Nun engt man im Wasserstrahlvakuum ein und versetzt den Rückstand mit 100 ecm Wasser. Man extrahiert mit Äther und wäscht die Ätherlösung mehrmals mit Wasser. Dann trocknet man über geglühtem Natriumsulfat und engt die Lösung auf etwa 100 ecm ein. Durch Versetzen mit ätherischer Salzsäure erhält man so das Dihydrochlorid des l-(3',4'-Dimethoxybenzyl)-4-(3",4",5"-trimethoxybenzoyl» ^"-oxypropyl)-piperazin. Aus wenig wasserfreiem Alkohol umkristallisiert, erhält man es in farblosen Kristallen vom Fp 231-233°. Ausbeute! 42 g = 76 % der Theorie.Dissolved 100 ecm of dimethylformamide and, after adding 5.4 g (= 0.1 mol) of sodium methylate at 50-60 ° with stirring, a solution of 29 g (= 0.1 mol) of 3,4,5-trimethoxybenzoic acid - ^ - chloropropyl ester in 50 ecm of dimethylformamide added dropwise within 1 hour. The mixture is then stirred at 100 ° for 12 hours. It is then concentrated in a water jet vacuum and 100 ecm of water are added to the residue. Extract with ether and wash the ethereal solution several times with water. Then it is dried over calcined sodium sulfate and the solution is concentrated to about 100 ecm. By adding ethereal hydrochloric acid, the dihydrochloride of 1- (3 ', 4'-dimethoxybenzyl) -4- (3 ", 4", 5 "-trimethoxybenzoyl ^" - oxypropyl) piperazine is obtained. Recrystallized from a little anhydrous alcohol, it is obtained in colorless crystals with a melting point of 231-233 °. Yield! 42 g = 76 % of theory.

Beispiel 3: Example 3 :

1- (2',3',4'-Trimethoxyphenäthyl)-4-(3",4",5"-trimethoxybertzoylß-oxypropyl)-piperazin-dihydrochlorid. 1- (2 ', 3', 4'-trimethoxyphenethyl) -4- (3 ", 4", 5 "-trimethoxybertzoylβ-oxypropyl) -piperazine dihydrochloride.

Zu einer Suspension von 23,4 g (= 0.1 Mol) 3,4,5—trimethoxybenzoesaurem Natrium in 100 ecm Dimethylsulfoxyd tropft man bei 30-40° unter Rühren eine Lösung von 40 g (= 0.1 Mol) 1- (2 ·', 3*,4' -Tr imethoxyphenäthyl) -4 - (ß-brompropyl) -piperazin in 100 ecm Dimethyl sulfoxyd. Man rührt 12 Stunden bei 50-60°. Dann engt man i.V. ein und versetzt den Rückstand mit 100 ecm Wasser. Man extrahiert sodann zweimal mit Benzol, wäscht die vereinigten Extrakte mehrmals mit Wasser und trocknet sie über geglühtem Natriumsulfat. Dann engt man im Wasserstrahlvakuum bei 40° auf ein kleines Volumen ein und versetzt mitA solution of 40 g (= 0.1 mol) 1- (2 · ' , 3 *, 4 '-Tr imethoxyphenäthyl) -4 - (ß-bromopropyl) -piperazine in 100 ecm dimethyl sulfoxide. The mixture is stirred at 50-60 ° for 12 hours. It is then concentrated in vacuo and 100 ecm of water are added to the residue. It is then extracted twice with benzene, the combined extracts are washed several times with water and dried over calcined sodium sulfate. Then it is concentrated in a water jet vacuum at 40 ° to a small volume and mixed with

0 0984 4M 8 9.8 BAD 0Rle)NAL -5-0 0984 4M 8 9.8 BAD 0Rle) NAL -5-

ID /UJOUID / UJOU

- 5 - ' . Se;:. 2"7GS- 5 - '. Se;:. 2 " 7 GS

slkc^oli.scher .Salzsäure bis zur konyosauran Reaktion» E^ er -?trtigeia Jtehen unter Eiskühl/ung saugt man das Kr istall J sat ab ·αη·:7. kristallisiert aus wenig wasserfreiem. Alkohol um..Slkc ^ oli. hydrochloric acid up to the konyosauran reaction » E ^ er -? trtigeia Jtehen under ice cooling one sucks off the crystal J sat · αη ·: 7. crystallizes from little anhydrous. Alcohol to ..

Man erhält so das Dihydrochlorid c»es l-(2' ,3' ,4 ' -Trr'^ethoxyrhenäthyl) -4-(3 ",4% 5"-trinethoxyberiZOyl,-'ß-oxypropyl) -pi^arasrin in farblosen Kristallen vom Fp 214-216°.This gives the dihydrochloride c »es l- (2 ', 3', 4 '-Trr' ^ ethoxyrhenethyl) -4- (3 ", 4% 5" -trinethoxyberiZOyl, - 'ß-oxypropyl) -pi ^ arasrin in colorless crystals of melting point 214-216 °.

Ausbeute: 40 g = 66 % der Theorie.Yield: 40 g = 66 % of theory.

In analoger TTeise wie in den vorstehenden Beispielen beschrieben, kann man die folgenden Substanzen herstellen: ^In an analogous manner as described in the previous examples, one can produce the following substances: ^

1.) 1-(3' ,4'-Dimethoxybenzyl·)-4-(3",4",5"-trimethoxybenzoylß-oxyäthyl)-piperazin-2 HCl Fp 169°(Zers.)1.) 1- (3 ', 4'-Dimethoxybenzyl ·) -4- (3 ", 4", 5 "-trimethoxybenzoylβ-oxyethyl) -piperazine-2 HCl m.p. 169 ° (decomp.)

2.) 1 - (3 ' , 4 · -Dimethoxybenzyl) -4 ~ (3 " ,A ", 5 " -tr imethoxybenzoy].-ß-oxypropyl)-piperazin-2 HCl Fp 2ie°(Zers.)2.) 1 - (3 ', 4 · -Dimethoxybenzyl) -4 ~ (3 " , A ", 5 "-tr imethoxybenzoy] .- ß-oxypropyl) -piperazine-2 HCl mp 2ie ° (dec.)

3.) 1 - (31,4' -Dimethoxybenzyl) -4- (3 ",4 ", 5 " -tr imethoxybenzoylß-cxy~y-methoxypropyl)-piperazin-2 HCl Fp l71°(Zers.)3.) 1 - (3 1 , 4 '-Dimethoxybenzyl) -4- (3 ", 4", 5 "-trimethoxybenzoylß-cxy ~ y-methoxypropyl) -piperazine-2 HCl mp 171 ° (dec.)

.) .7 -(3 ' ,4 ' -Dimethoxybenzyl) -4- (3 ",4" , 5 " -trimethoxybenzoyl- <£~oxybutyl)-piperazin-2 HCl " Fp 202o(Zers.).) .7 - (3 ', 4' -Dimethoxybenzyl) -4- (3 ", 4", 5 "-trimethoxybenzoyl- <£ ~ oxybutyl) -piperazine-2 HCl" m.p. 202 o (dec.)

5.) 1- (3', 4 · -Dimethoxyphenäthyl) -4 - (3 ", 4 ". 5 " -tr iTnethoxybensoyl- j ß-oxyäthyl)-piperazin-2 HCl Fp 229o(Zers.) 5. ) 1- (3 ' , 4 · -Dimethoxyphenäthyl) -4 - (3 ", 4". 5 " -tr iTnethoxybensyl- j ß-oxyäthyl) -piperazin-2 HCl m.p. 229 o (dec.)

6.) 1-(3·,4'-DimethoxyphenSthyl)-4-(3",4",5"-tr imethoxybenzoyl-2T-oxypropyl)-piperazin-2 HCl Fp 226°(Zers.)6.) 1- (3 ·, 4'-DimethoxyphenSthyl) -4- (3 ", 4 ", 5 "-tr imethoxybenzoyl-2T-oxypropyl) -piperazine-2 HCl mp 226 ° (dec.)

7.) 1-(3',4·-Dimethoxyphe nSthyl)-4-(3",4",5"-tr imethoxybenzoy1-ß-oxypropyl)-piperazin-2 HCl· Fp 224°(Zers.)7.) 1- (3 ', 4 · -Dimethoxyphe n-thyl) -4- (3 ", 4", 5 "-tr imethoxybenzoy1-ß-oxypropyl) -piperazine-2 HCl · mp 224 ° (dec.)

λ.) 1-(3·,4'-Dimethoxyρhenäthyl)-4-(3"r4",5"-trimethoxybenzoyly-oxybutyl)-niperazin -2 HCl · Fp 223°(Zers.)λ.) 1- (3 ·, 4'-Dimethoxyρhenäthyl) -4- (3 " r 4", 5 "-trimethoxybenzoyly-oxybutyl) -niperazine -2 HCl · Mp 223 ° (dec.)

9.) l-(3' ,4l-Dimethoxyphenäthyl)-4-(3l^4",5"-trimetl^oxybenzoylß-oxy-c,a-dimethylathyl)-piperazin-2 HCl Fp 219°(Zers.)9.) 1- (3 ', 4 l -Dimethoxyphenäthyl) -4- (3 l ^ 4 ", 5" -trimetl ^ oxybenzoylß-oxy-c, a-dimethylethyl) -piperazine-2 HCl mp 219 ° (dec. )

IO,} X-(3'- 4'-Dimsthoxyphenylpropyl)-4-(3",4",R"-tr ime thoxybenzoy1-IO,} X- (3'- 4'-Dimsthoxyphenylpropyl) -4- (3 ", 4", R "-tr ime thoxybenzoy1-

pi per azin-2 HCl ' Fn l-9.r6(Zers·)pi per azin-2 HCl 'Fn l-9. r6 (dec)

0 Q 9 8 4 Λ / 1 B 9 8 _ 60 Q 9 8 4 Λ / 1 B 9 8 _ 6 "

BADOBIGiNAl.BADOBIGiNAl.

Ref. 2769Ref. 2769

' 11.) l-(3l f4I-Diicethoxyphenylpropy.l)-4-(311 #4",5"-triraetlioxybenzoyl- jf -oxypropyi)-p-iperazin-2 HCl Fp 21O° (Zers.)11.) l- (3 l f 4 I -diicethoxyphenylpropy.l) -4- (3 11 # 4 ", 5" -triraetlioxybenzoyl- jf -oxypropyi) -p-iperazine-2 HCl mp 210 ° (decomp.)

12.) 1-(3',4f -Diracithoxyphenylpropyl) -4-(3" ,4",5"-trimethoxybenzoylß-oxypropyl)-piperazin-2 HCl Fp 208° (Zers.)12.) 1- (3 ', 4 f -Diracithoxyphenylpropyl) -4- (3 ", 4", 5 "-trimethoxybenzoylß-oxypropyl) -piperazine-2 HCl mp 208 ° (dec.)

13.) 1-C31 f4t-Dimethoxyphenylpropyl)-4-(3",4"#5"-trimefhoxybenzoyljT-oxybutyl)-piper azin-2 HCl Fp 217° (Zers.)13.) 1-C3 1 f 4 t -Dimethoxyphenylpropyl) -4- (3 ", 4"# 5 "-trimefhoxybenzoyljT-oxybutyl) -piper azine-2 HCl mp 217 ° (dec.)

.) 1—( 3', 4 * -D imethoxyphenyl isopropyl) -4 - ( 3 " ,4 ", 5 " -tr imethoxybenzoyl -.) 1- (3 ', 4 * -D imethoxyphenyl isopropyl) -4 - (3 ", 4", 5 "-tr imethoxybenzoyl -

ß-oxyäthyl)-piperazin-2 HCl Fp 222° (Zers.)ß-oxyethyl) piperazine-2 HCl mp 222 ° (decomp.)

.) l-(3f /4l-Dimethoxyphenylisopropyl)-4-(3I1,4",5"-trimethoxybenzoyl-.) l- (3 f / 4 l -Dimethoxyphenylisopropyl) -4- (3 I1 , 4 ", 5" -trimethoxybenzoyl-

£"~oxypropyl)-piper azin-2 HCl Fp 220° (Zers.)£ "~ oxypropyl) -piper azine-2 HCl mp 220 ° (decomp.)

16.) l-(3f #4'-D.imethoxyplienylisopropyl)-4-(3I'f4H #5u-trimetTioxybenzoylß-oxypropyl)-piperazin-2 HCl Fp 222° (Zers.)16.) 1- (3 f # 4'-D.imethoxyplienylisopropyl) -4- (3 I ' f 4 H # 5 u -trimet-dioxybenzoylß-oxypropyl) -piperazine-2 HCl mp 222 ° (dec.)

17.) l-(3· ,4l-Bimefchoxyphenyli3opropyl·)-4-ί3ll,4"l,5ll-trimetlloxybenzoylys-oxybutyl)-piperazin-2 HCl Fp 234° (Zers.)17.) l- (3 ·, 4 l -Bimefchoxyphenyli3opropyl ·) -4-ί3 ll , 4 " l , 5 ll -trimetlloxybenzoyly s -oxybutyl) -piperazine-2 HCl mp 234 ° (dec.)

18.) l-(2' ,3' ,4· -Trimethoxyphenäthyl) ^-^"^"^"-trimethoXybenZoylß-oxyäthyl)-piperazin-2 HCl Fp 211° (Zers.)18.) 1- (2 ', 3', 4 · -trimethoxyphenethyl) ^ - ^ "^" ^ "- trimethoXybenZoylß-oxyethyl) -piperazine-2 HCl mp 211 ° (decomp.)

19.) l-(2e f3G ,4*-Trimethoxyptienäthyl)-4-(3",4"f 5 "-tr imetlioxybenzoyl-%—oxypropyl)-piperäzin-2 HCl Fp 227° (Zers.)19.) 1- (2 e f 3 G , 4 * -trimethoxyptienethyl) -4- (3 ", 4" f 5 "-tr imetlioxybenzoyl- % -oxypropyl) -piperazine-2 HCl mp 227 ° (decomp.)

20.) 1-(2·,3 ·,4' -Trimethoxyphenäthyl) -4-(3",4",5"-trimethoxybenzoyl-Jj-oxybutyl)-piperazin-2 HCl Fp 224° (Zers.)20.) 1- (2 ·, 3 ·, 4 '-trimethoxyphenethyl) -4- (3 " , 4", 5 "-trimethoxybenzoyl-Jj-oxybutyl) -piperazine-2 HCl mp 224 ° (dec.)

21.) l-(2· ,3' ,4l-Trimethöxyphenylpropyl)-4-(3",4",5"-trimethoxybenzoylß-oxyäthyl)-piperazin-2 HCl Fp 188° (Zers.)21.) 1- (2 ·, 3 ', 4 l -trimethoxyphenylpropyl) -4- (3 ", 4", 5 "-trimethoxybenzoylß-oxyethyl) -piperazine-2 HCl mp 188 ° (decomp.)

22.)l-(2r ,3' ,4*-Trimethoxyphenylpropyl)-4-(-3",4",5"-trimethoxybenzoyl- ^oxypropyl)-piperazin-2 HCl Fp 2O5Q (Zers.)22.) 1- (2 r , 3 ', 4 * -trimethoxyphenylpropyl) -4 - (- 3 ", 4", 5 "-trimethoxybenzoyl- ^ oxypropyl) -piperazine-2 HCl mp 2O5 Q (dec.)

23.) l-(2·,31 /4t-Trimethoxyphenylpropyl)-4-(3ll f4",FM-trimethoxybenzoyl-ß-oxypropyl)-piperazin-2 HCl Fp 2O3° (Zers.)23) l- (2 x 3 1/4 -Trimethoxyphenylpropyl) -4- (3 f ll t 4 ", F M -trimethoxybenzoyl-ß-oxopropyl) piperazine-2 HCl mp 2O3 ° (dec.)

24.) l-(2' ,31 f4r-Triraethoxyphenylpropyl)-4-(3"i4ll,511-trimethoxybeB2oyl-2f-oxybutyl)-piperazin-2 HCl Fp 218° (Zers.)24.) 1- (2 ', 3 1 f 4 r -triraethoxyphenylpropyl) -4- (3 " i 4 ll , 5 11 -trimethoxybeB2oyl-2f-oxybutyl) -piperazine-2 HCl mp 218 ° (decomp.)

25.) l-(2' f 31 r4t-Trimethoxyphenylisopropyl)-4-(3"f4II,5"-trimetlioxybenzoi ß-oxyathyi)-piperazin-2 HCl Fp 225° (Zers.)25.) l- (2 ' f 3 1 r 4 t -trimethoxyphenylisopropyl) -4- (3 " f 4 II , 5" -trimetlioxybenzoi ß-oxyathyi) -piperazine-2 HCl mp 225 ° (dec.)

26.) l-(2l,al,4l-Trimethoxyphenylisopropyl)-4-(3M f.4",5"-trimethoxybenzoyl-Jf-oxypropyl)-piperazin-2 HCL Fp 226° (Zers.)26.) 1- (2 l , a l , 4 l -trimethoxyphenylisopropyl) -4- (3 M f .4 ", 5" -trimethoxybenzoyl-Jf-oxypropyl) -piperazine-2 HCl melting point 226 ° (decomp.)

27.) l-(2l,3t,4l-Trimethoxyph?pylisopropyl>-4-(3li f4M,5II-triTnethoxybenzoyl-jr-Tpxyb\ityl)-pipera2in-2 HCl Fp 216° (Zers.)27.) l- (2 l , 3 t , 4 l -trimethoxyph? Pylisopropyl> -4- (3 li f 4 M , 5 II -triTnethoxybenzoyl-jr-Tpxyb \ ityl) -pipera2in-2 HCl mp 216 ° (dec .)

009844/1898 BAD öR "7"009844/1898 BAD öR " 7 "

Claims (1)

- 7 - Ref. 2769- 7 - Ref. 2769 PatentanspruchClaim Verfahren zur Herstellung von Derivaten des Piperazine der allgemeinen FormelProcess for the preparation of derivatives of piperazine of the general formula ROR1 ROR 1 in der R einen Alkylrest mit 1 oder 2 C-Atomen, R, Wasserstoff oder einen Alkoxyrest mit 1 oder 2 C-Atomen und A.. und A2 gerad- oder verzweigkettige Alkylenreste mit 1 bis 4 C-Atomen bedeuten, dadurch gekennzeichnet, daß man nach an sich bekannten Methoden entwederin which R is an alkyl radical with 1 or 2 carbon atoms, R is hydrogen or an alkoxy radical with 1 or 2 carbon atoms and A .. and A are 2 straight or branched alkylene radicals with 1 to 4 carbon atoms, characterized in that, that one according to methods known per se either a) eine Trxalkoxybenzoesaure der allgemeinen Formela) a trxalkoxybenzoic acid of the general formula HOOC-4 7>—ORHOOC-4 7 > -OR 'OR'OR bzw. deren funktioneile Derivate mit einem Alkohol der allgemeinen Formelor their functional derivatives with an alcohol of the general formula gegebenenfalls in Anwesenheit eines säurebindenden Mittels umsetzt, oder daß manoptionally reacted in the presence of an acid-binding agent, or that one b) einen Trialkoxybenzoesäurehalogenalkylester der allgemeinen Formelb) a trialkoxybenzoic acid haloalkyl ester of the general formula COO-A2-HaI,COO-A 2 -HaI, in der Hai ein Halogenatom ist, mit einem Piperazinderivat der allgemeinen Formelin which Hai is a halogen atom with a piperazine derivative the general formula ■ - 8 -■ - 8 - OQ9844/1898OQ9844 / 1898 BAD ORIGINALBATH ORIGINAL Ref. 276 9Ref. 276 9 Aj - N NF,Aj - N NF, gegebenenfalls ir> Anwesenheit eines säurebindenrien f xttels, kondensier·1-, oder diß manif necessary, in the presence of an acid-binding agent, condensation 1 -, or one c) ein Λ13 -iljo?]z eiriei- Tr.'allcox/bGnjines^ure der allgemeinen Formelc) a Λ13 -iljo?] z eiriei- Tr.'allcox / bGnjines ^ ure of the general formula . O.U. O.U HOGC-HOGC mit einen Piperazinderi^t der c] ?geH:eir.en Tormelwith a Piperazinderi ^ t of the c]? geH: eir.en Tormel umsetze.implement. S - A0 - HaiS - A 0 - shark 009844/1898009844/1898 BAD ORJGiNALBAD ORJGiNAL
DE19661670360 1966-07-02 1966-07-02 Process for the preparation of derivatives of piperazine Pending DE1670360A1 (en)

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BE (1) BE700811A (en)
CH (1) CH489509A (en)
DE (1) DE1670360A1 (en)
DK (1) DK120133B (en)
ES (1) ES342460A1 (en)
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2807169A1 (en) * 1977-02-25 1978-09-14 Richter Gedeon Vegyeszet A NEW PYRIDYL PIPERAZINE DERIVATIVE AND METHOD FOR THE PRODUCTION THEREOF

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2280634A2 (en) * 1974-07-31 1976-02-27 Synthelabo 4-Phenyl-piperazino-alkyl anthranilate deriv prepn. - from 2-nitro-benzoic acid via acid halide or salts, condensation with phenyl-piperazino-alkyl radical and reduction
JPS53112887A (en) * 1977-03-12 1978-10-02 Nippon Shinyaku Co Ltd Production of n-substituted trialkoxybenzylpiperazine derivative
JPS53112886A (en) * 1977-03-12 1978-10-02 Nippon Shinyaku Co Ltd Production of n-substituted trialkoxybenzylpiperazine derivative
CN117100751A (en) * 2017-06-20 2023-11-24 安布里亚制药公司 Compositions and methods for improving cardiac metabolic efficiency

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2807169A1 (en) * 1977-02-25 1978-09-14 Richter Gedeon Vegyeszet A NEW PYRIDYL PIPERAZINE DERIVATIVE AND METHOD FOR THE PRODUCTION THEREOF

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IL28197A (en) 1971-05-26
GB1127993A (en) 1968-09-25
AT272354B (en) 1969-07-10
FR1530040A (en) 1968-06-21
FR7173M (en) 1969-08-11
CH489509A (en) 1970-04-30
ES342460A1 (en) 1968-09-16
BE700811A (en) 1968-01-02
AT271481B (en) 1969-06-10
NL6708818A (en) 1968-01-03

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