CA1055492A - Piperazine-and homopiperazine-monoalkanol esters and a process of production thereof - Google Patents
Piperazine-and homopiperazine-monoalkanol esters and a process of production thereofInfo
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- CA1055492A CA1055492A CA189,574A CA189574A CA1055492A CA 1055492 A CA1055492 A CA 1055492A CA 189574 A CA189574 A CA 189574A CA 1055492 A CA1055492 A CA 1055492A
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- 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
- C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—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 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
- C07D295/088—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 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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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
A B S T R A C T
Piperazine - or homopiperazine - monoalkanol esters are disclosed which are represented by the formula:
where R represents a phenyl group which may be substituted with a lower alkyl group, a lower alkoxy group or a halogen atom, or a styrylgroup or a 2-,3- or 4- pyridyl group which may be substituted with a lower alkoxy group or a salt thereof.
The above compound is prepared by reacting a piperazine- or homopiperazine- monoalkanol represented by the formula:
Piperazine - or homopiperazine - monoalkanol esters are disclosed which are represented by the formula:
where R represents a phenyl group which may be substituted with a lower alkyl group, a lower alkoxy group or a halogen atom, or a styrylgroup or a 2-,3- or 4- pyridyl group which may be substituted with a lower alkoxy group or a salt thereof.
The above compound is prepared by reacting a piperazine- or homopiperazine- monoalkanol represented by the formula:
Description
Si4~Z
NOVEL PIPERAZINE - ~ND HOMOPIPERAZINE-MONOALKANOL
ESTERS AND A PROCESS OF PRODUCTION THEREOF
The present invention relates to a process of producing a piperazine-or homopiperazine-monoalkanol ester represented by the formula: -R
H~ ~ _ (CH2) - O - C - R
where R is a phenyl group which may be substituted with a lower alkyl group, a lower alkoxy group or a halogen atom, or a styryl group or 2-, 3- or 4- pyridyl group which may be substituted with a lower alkoxy group; and n and m are 2 or 3, respectively, and a salt thereof.
According to the present invention, the compound represen-ted by the formula (I) above can be produced by esterificationo~ a piperazine- or homopiperazine-monoalkanol represented by the formula: ~
H\ ~ _ (CH2) - OH (II) (C 2)n where n and m each represents 2 or 3, or a salt thereof, with a benzoic acid which may be substituted with a lower alkyl group, a lower alkoxy group or a halogen atom, or a cinnamic acid or a nicotine acid compound including nicotinic acid, isonicotinic acid and picolinic acid which may be substituted with a lower alkoxy group.
The esterification in accordance with the present invention proceeds successfully in the presence of a dehydrating agent. Spe-cific examples of dehydrating agent include hydrochloric acid, sul-furic acid, p-toluene sulfonic acid, N,N dicyclohexylcarbodiim-ide, etc. Among these, p-toluene sulfonic acid is most preferred.
-1- ~ ' "
.
s~y~
Any solvents can be employed in the esterification in accordance with the present invention unless the solvents prevent the reaction.
Typical examples of solvents are ben2ene, toluene, xylene, dioxanr chloroform, tetrahydrofuran,e-tc., preferably benzene or dioxane is employed. The preferred reaction temperature is, in general, above room temperature, more preferably, near a boiling point of the solvents employedO
The product (I) produced in accordance with the present invention can be converted into the corresponding salt using an inorganic or organic acid in a conventional manner. Typical examples of inorganic acids include hydrohalic acid (hydrochloric acid, hydrobromic acid), sulfuric acid, phosphoric acid, etc.
The organic acids which can be employed in the present invention are typified by lactic acid, maleic acid, succinic acid, tartaric acid, salicylic acid, oxalic acid, citric acid, benzoic acid,etc.
The novel compound (I) in accordance with the present invention exhibits analgetic, coronary vasodilative, anti-convulsant, blood pressure decreasing properties, which is par-ticularly useful for therapeutic agents for circulation diseases and is further useful for an intermediate ~or other therapeutic agents.
The following examples are merely illustrative and are not to be considered as limiting the invention.
EX~MPLE I
In 150 ml of absolute benzene there were dissolved 2.6g of l-piperazineethanol, 5.5 g of 2, 3, 4-trimethoxybenzoic acid and 19 g of p-toluene sulfonic acid. The solution was heated for 15 hours to reflu~ while removing the formed water. After the reaction liquid was cooled, the reaction li~uid was washed with 15% potassium carbonate and then extracted with 10% hydrochloric -~
, :,~ ' '~ -' ', . , ' '' , ' ' : ,, . ,' , , :. . , : . . .: .: . . , , ' . - : , . , s~
acid After washing the aqueous layer with ether, the system was rendered alkaline with pota~sium carbonate to extract with ~ -ether. The ethereal layer was dehydrated with a Glauber ' 6 salt and then the ether was removed by distillationO The resultant residue was subjected:to chromatography using silica gel to give a colorless transparent liquid. The liquid was treated in a con-ventional manner to convert into the maleic acid salt thereof.
Upon crystallization from ethanol, l-piperazineethanol 2, 3, ~-trimethoxybenzoate maleate was obtained, a melting point of which was 140-141~Co The Y~~eld was 46%.
Elemental Analysis: as C H ~ o .2(C H o ) H o 16 2~ 2 5 4 4 4 2 Calculated: C:50O 49 H:5O98 ~:5.00 Found: C: 50.37 H:5097 ~:4.88 EX~MPLE 2 In 150 ml of absolute dioxane there were dissolved 2 88 g .
of l-piperazinepropanol, 3.64 g of p-fluorobenzoic acid and 19 g of p-toluene sulfonic acid. While removing the formed water, the solution was heated ~or 16 hours to refluxO A~ter the dioxane ; ~:~was removed from the reaction liquid, ether was added to the .
residue~ The system was extracted with 10% hydrochloric acidO :
The aqueous layer was rendered alkaline using potassium carbonate and then extracted with ether. The ethereal layer was dehydrated with a Glauber's salt. The ether was removed from the system by distillation. rrhe resultant residue was subjected to chrom-atography using silica gel to give a colorless transparent liquid.
The liqul~d was converted into the hydrochloride thereof in accordance with a conventional manner. Upon recrystallization from ethanol, l-piperazinepropanol p-fl~robenzoate hydrochloride was obtained, a melting point of which was 196-199C. r~he Yield was 56%.
,~ .
", "
5S~
Elemental Analysis: as Cl~HlgN202F.2HCl-H20 Calculated: C : 47.07 H : 6.49 N : 7.84 Found C : 46.83 H : 6.56 N : 7.84 In 150 ml of absolute benzene there were dissolved 1.44 g of l-homopiperazineethanol and 9.5 g of p-toluene sulfonic acid.
To the solution 2.75 g of 2,3,4-trimethoxybenzoic acid was added.
The system was heated for 16 hours to reflux while removing the formed water. The reaction liquid was co~led, washed with 15%
potassium carbonate and then extracted with 10% HCl. After the aqueous layer was washed with ether and then rendered alkaline with potassium carbonate, the solution was extracted with ether.
After the ethereal layer was dehydrated with a Glauber's salt, the ether was distilled off. The resultant residue was subjected to chro-matography using silica gel to obtain a colorless transparent liquid.
The liquid was converted into the maleic acid salt thereof in accor- -dance with a conventional manner. Upon recrystallization from ethanol, l-homopiperazineethanol 2,3,4-trimethoxybenzoate maleate ~ ... . ..
was obtained, a melting point of which was 112~113C. The yield was 59%. Elemental Analysis: as C17~126N205 2 (C4H404) 2 Calculated: C : 51.02 H : 6.17 N : 4.76 Found: C : 50.91 H : 6.25 N : 4.71 _XAMPLE 4 In 150 ml of absolute benzene there were dissolved 2.83 g of l-piperazinepropanol, 3.2 g of isonicotinic acid and 30.4 g of p-toluene sulfonic acid. The solution was heated for ]5 hours to reflux while removing the formed water. The reaction liquid was cooled, washed with 15% potassium carbonate and then extracted with 10% hydrochloric acid. After the a~ueous layer was washed .
,, ~' . ' ' ' ' . ' ' . , ': ' with ether) the system was rendered alkaline with potas~ium carbonate and then extracted with ether. After the ethereal layer was dehydrated with a Glauber's salt, the ether was distilled off. The resultant residue was sub~ected to chrom-atography using silica gel to obtain a colorless transparentliquid. After the liquid was converted into the hydrochlDride thereof in accordance with a conventional manner. It was re-crystallized from ethanol to give l-piperazinepropanol isoni-cotinate hydrochloride. The melting point thereof was 201-202~.
The Yield was 66%.
Elemental Analysis: as C H N 0 .2HCl .H O.
Calculated: C : 45O89 H : ~.81 M : 12.35 Found: C : 45.75 H : 6.92 N : 12.31 In 150 ml of absolute benzene there were dissolved 3.04 g of l-homopiperazinepropanol, 2.85 g of picolinic acid and 2.73 g of p-toluene sulfonic acid. The solution was heated for 16 hours to reflux while removing the formed water. The reaction liquid was cooled, washed with 15% potassium carbonate and then extracted with 10% hydrochloric acid. The aqueous layer was washed with ether and then rendered alkaline with potassium carbonate to extract with ether. After the ethexeal layer was dehydrated over a ~lauber's salt, the ether was distilled off. The resultant residue was subject to chromatography using silica gel to give a colorless transparent liquid. The liquid was converted into the maleic acid salt thereof in accordance with a conventional manner.
Upon recrystallizaiion of the maleic acid salt from ethanol, 1-homopiperazinepropanol picolinate maleate was obtained, a melting point of which was 105~107C. ~he Yield was 47%.
El~mental Analysis: as C14H21N3O2 4 4 4 2 Calculated: C : 51.46 H 6.09 N : 8.18 Found: C : 51.30 H : 6.22 N : 8.14 Example 6 In 150 ml of absolute benzene there were clissolved 1.95 g of l-piperazineethanol and 14.2 g of p-toluene sulfonic acid. To the solution 2.89 g of cinn~nic acid was added. The ~ystem was heated for 16 hours to reflux while removing the formed water. The reac-tion liquid was cooled, washed with 15% potassium carbonate and ;
then extracted with 10% hydrochloric acid. After the aqueous layer was washed with ether, the system was rendered alkaline to extract with ether. After the ethereal layer was dehydrated over a Glauber's salt, the ether was distilled off. The resultant resi-due was subjected to chromatography using silica gel to give a colorless transparent liquid. The liquid was converted into the hydrochloride thereof. Upon recrystallization from ethanol, 1-piperazineethanol cinnamate hydrochloride was obtained. The mel-ting point thereof 184-1~7 C. The yield was 53%. ~ -Elemental Analysis: as C15H20N202 .2HCl H20 Calculated: C : 48.66 H : 6.53 N : 7.56 Found: C : 48.61 H : 6.60 N : 7.48 Ex~mple 7 In 1.50 ml o~ absolute benzene there were dissolved 1.58 g of 1-homopiperazinepropanol, 3.09 g of 2,3,4-trimethoxycinnamic acid and 9.5 g of p-toluene sulfonic acid. The solution was hea-ted for 16 hours to reflux while removing the formed water. The 25 reaction liquid was cooled, washed with 15% potassium carbonate and -then extracted with l~/o hydrochloric acid. After the aqueous layer was washed with ether, the system was rendered alkaline with pot-assium carbonate to extract with ether. After the ethereal layer was dehydrated over a Glauber's sa]t, the ether was distilled off.
The resultant residue was subjected to chromatography using silica gel to obtain a colorless transpar~nt liquid. I~e liquid was con~er~d . .
... , .. . . ~ , . . . . . .
'", , ,'' ' " '. ' " ., ",' ' ,"' ' ' ' ', ', '"' ', ' ~ '; ' " . ' ' . . . .
S5~
into the oxala-te thereof in accordallce with conventiorlal manner.
Upon recrystallization from methanol, l-homopiperazinepropanol
NOVEL PIPERAZINE - ~ND HOMOPIPERAZINE-MONOALKANOL
ESTERS AND A PROCESS OF PRODUCTION THEREOF
The present invention relates to a process of producing a piperazine-or homopiperazine-monoalkanol ester represented by the formula: -R
H~ ~ _ (CH2) - O - C - R
where R is a phenyl group which may be substituted with a lower alkyl group, a lower alkoxy group or a halogen atom, or a styryl group or 2-, 3- or 4- pyridyl group which may be substituted with a lower alkoxy group; and n and m are 2 or 3, respectively, and a salt thereof.
According to the present invention, the compound represen-ted by the formula (I) above can be produced by esterificationo~ a piperazine- or homopiperazine-monoalkanol represented by the formula: ~
H\ ~ _ (CH2) - OH (II) (C 2)n where n and m each represents 2 or 3, or a salt thereof, with a benzoic acid which may be substituted with a lower alkyl group, a lower alkoxy group or a halogen atom, or a cinnamic acid or a nicotine acid compound including nicotinic acid, isonicotinic acid and picolinic acid which may be substituted with a lower alkoxy group.
The esterification in accordance with the present invention proceeds successfully in the presence of a dehydrating agent. Spe-cific examples of dehydrating agent include hydrochloric acid, sul-furic acid, p-toluene sulfonic acid, N,N dicyclohexylcarbodiim-ide, etc. Among these, p-toluene sulfonic acid is most preferred.
-1- ~ ' "
.
s~y~
Any solvents can be employed in the esterification in accordance with the present invention unless the solvents prevent the reaction.
Typical examples of solvents are ben2ene, toluene, xylene, dioxanr chloroform, tetrahydrofuran,e-tc., preferably benzene or dioxane is employed. The preferred reaction temperature is, in general, above room temperature, more preferably, near a boiling point of the solvents employedO
The product (I) produced in accordance with the present invention can be converted into the corresponding salt using an inorganic or organic acid in a conventional manner. Typical examples of inorganic acids include hydrohalic acid (hydrochloric acid, hydrobromic acid), sulfuric acid, phosphoric acid, etc.
The organic acids which can be employed in the present invention are typified by lactic acid, maleic acid, succinic acid, tartaric acid, salicylic acid, oxalic acid, citric acid, benzoic acid,etc.
The novel compound (I) in accordance with the present invention exhibits analgetic, coronary vasodilative, anti-convulsant, blood pressure decreasing properties, which is par-ticularly useful for therapeutic agents for circulation diseases and is further useful for an intermediate ~or other therapeutic agents.
The following examples are merely illustrative and are not to be considered as limiting the invention.
EX~MPLE I
In 150 ml of absolute benzene there were dissolved 2.6g of l-piperazineethanol, 5.5 g of 2, 3, 4-trimethoxybenzoic acid and 19 g of p-toluene sulfonic acid. The solution was heated for 15 hours to reflu~ while removing the formed water. After the reaction liquid was cooled, the reaction li~uid was washed with 15% potassium carbonate and then extracted with 10% hydrochloric -~
, :,~ ' '~ -' ', . , ' '' , ' ' : ,, . ,' , , :. . , : . . .: .: . . , , ' . - : , . , s~
acid After washing the aqueous layer with ether, the system was rendered alkaline with pota~sium carbonate to extract with ~ -ether. The ethereal layer was dehydrated with a Glauber ' 6 salt and then the ether was removed by distillationO The resultant residue was subjected:to chromatography using silica gel to give a colorless transparent liquid. The liquid was treated in a con-ventional manner to convert into the maleic acid salt thereof.
Upon crystallization from ethanol, l-piperazineethanol 2, 3, ~-trimethoxybenzoate maleate was obtained, a melting point of which was 140-141~Co The Y~~eld was 46%.
Elemental Analysis: as C H ~ o .2(C H o ) H o 16 2~ 2 5 4 4 4 2 Calculated: C:50O 49 H:5O98 ~:5.00 Found: C: 50.37 H:5097 ~:4.88 EX~MPLE 2 In 150 ml of absolute dioxane there were dissolved 2 88 g .
of l-piperazinepropanol, 3.64 g of p-fluorobenzoic acid and 19 g of p-toluene sulfonic acid. While removing the formed water, the solution was heated ~or 16 hours to refluxO A~ter the dioxane ; ~:~was removed from the reaction liquid, ether was added to the .
residue~ The system was extracted with 10% hydrochloric acidO :
The aqueous layer was rendered alkaline using potassium carbonate and then extracted with ether. The ethereal layer was dehydrated with a Glauber's salt. The ether was removed from the system by distillation. rrhe resultant residue was subjected to chrom-atography using silica gel to give a colorless transparent liquid.
The liqul~d was converted into the hydrochloride thereof in accordance with a conventional manner. Upon recrystallization from ethanol, l-piperazinepropanol p-fl~robenzoate hydrochloride was obtained, a melting point of which was 196-199C. r~he Yield was 56%.
,~ .
", "
5S~
Elemental Analysis: as Cl~HlgN202F.2HCl-H20 Calculated: C : 47.07 H : 6.49 N : 7.84 Found C : 46.83 H : 6.56 N : 7.84 In 150 ml of absolute benzene there were dissolved 1.44 g of l-homopiperazineethanol and 9.5 g of p-toluene sulfonic acid.
To the solution 2.75 g of 2,3,4-trimethoxybenzoic acid was added.
The system was heated for 16 hours to reflux while removing the formed water. The reaction liquid was co~led, washed with 15%
potassium carbonate and then extracted with 10% HCl. After the aqueous layer was washed with ether and then rendered alkaline with potassium carbonate, the solution was extracted with ether.
After the ethereal layer was dehydrated with a Glauber's salt, the ether was distilled off. The resultant residue was subjected to chro-matography using silica gel to obtain a colorless transparent liquid.
The liquid was converted into the maleic acid salt thereof in accor- -dance with a conventional manner. Upon recrystallization from ethanol, l-homopiperazineethanol 2,3,4-trimethoxybenzoate maleate ~ ... . ..
was obtained, a melting point of which was 112~113C. The yield was 59%. Elemental Analysis: as C17~126N205 2 (C4H404) 2 Calculated: C : 51.02 H : 6.17 N : 4.76 Found: C : 50.91 H : 6.25 N : 4.71 _XAMPLE 4 In 150 ml of absolute benzene there were dissolved 2.83 g of l-piperazinepropanol, 3.2 g of isonicotinic acid and 30.4 g of p-toluene sulfonic acid. The solution was heated for ]5 hours to reflux while removing the formed water. The reaction liquid was cooled, washed with 15% potassium carbonate and then extracted with 10% hydrochloric acid. After the a~ueous layer was washed .
,, ~' . ' ' ' ' . ' ' . , ': ' with ether) the system was rendered alkaline with potas~ium carbonate and then extracted with ether. After the ethereal layer was dehydrated with a Glauber's salt, the ether was distilled off. The resultant residue was sub~ected to chrom-atography using silica gel to obtain a colorless transparentliquid. After the liquid was converted into the hydrochlDride thereof in accordance with a conventional manner. It was re-crystallized from ethanol to give l-piperazinepropanol isoni-cotinate hydrochloride. The melting point thereof was 201-202~.
The Yield was 66%.
Elemental Analysis: as C H N 0 .2HCl .H O.
Calculated: C : 45O89 H : ~.81 M : 12.35 Found: C : 45.75 H : 6.92 N : 12.31 In 150 ml of absolute benzene there were dissolved 3.04 g of l-homopiperazinepropanol, 2.85 g of picolinic acid and 2.73 g of p-toluene sulfonic acid. The solution was heated for 16 hours to reflux while removing the formed water. The reaction liquid was cooled, washed with 15% potassium carbonate and then extracted with 10% hydrochloric acid. The aqueous layer was washed with ether and then rendered alkaline with potassium carbonate to extract with ether. After the ethexeal layer was dehydrated over a ~lauber's salt, the ether was distilled off. The resultant residue was subject to chromatography using silica gel to give a colorless transparent liquid. The liquid was converted into the maleic acid salt thereof in accordance with a conventional manner.
Upon recrystallizaiion of the maleic acid salt from ethanol, 1-homopiperazinepropanol picolinate maleate was obtained, a melting point of which was 105~107C. ~he Yield was 47%.
El~mental Analysis: as C14H21N3O2 4 4 4 2 Calculated: C : 51.46 H 6.09 N : 8.18 Found: C : 51.30 H : 6.22 N : 8.14 Example 6 In 150 ml of absolute benzene there were clissolved 1.95 g of l-piperazineethanol and 14.2 g of p-toluene sulfonic acid. To the solution 2.89 g of cinn~nic acid was added. The ~ystem was heated for 16 hours to reflux while removing the formed water. The reac-tion liquid was cooled, washed with 15% potassium carbonate and ;
then extracted with 10% hydrochloric acid. After the aqueous layer was washed with ether, the system was rendered alkaline to extract with ether. After the ethereal layer was dehydrated over a Glauber's salt, the ether was distilled off. The resultant resi-due was subjected to chromatography using silica gel to give a colorless transparent liquid. The liquid was converted into the hydrochloride thereof. Upon recrystallization from ethanol, 1-piperazineethanol cinnamate hydrochloride was obtained. The mel-ting point thereof 184-1~7 C. The yield was 53%. ~ -Elemental Analysis: as C15H20N202 .2HCl H20 Calculated: C : 48.66 H : 6.53 N : 7.56 Found: C : 48.61 H : 6.60 N : 7.48 Ex~mple 7 In 1.50 ml o~ absolute benzene there were dissolved 1.58 g of 1-homopiperazinepropanol, 3.09 g of 2,3,4-trimethoxycinnamic acid and 9.5 g of p-toluene sulfonic acid. The solution was hea-ted for 16 hours to reflux while removing the formed water. The 25 reaction liquid was cooled, washed with 15% potassium carbonate and -then extracted with l~/o hydrochloric acid. After the aqueous layer was washed with ether, the system was rendered alkaline with pot-assium carbonate to extract with ether. After the ethereal layer was dehydrated over a Glauber's sa]t, the ether was distilled off.
The resultant residue was subjected to chromatography using silica gel to obtain a colorless transpar~nt liquid. I~e liquid was con~er~d . .
... , .. . . ~ , . . . . . .
'", , ,'' ' " '. ' " ., ",' ' ,"' ' ' ' ', ', '"' ', ' ~ '; ' " . ' ' . . . .
S5~
into the oxala-te thereof in accordallce with conventiorlal manner.
Upon recrystallization from methanol, l-homopiperazinepropanol
2,3,4-trimethoxycinnamate oxalate was obtained, a melting point of which was 156-158 C. The yield was 48%.
Elemental analysis: as C20H28N2O5-2C2H2O4 H2O
calculated: C : 50.17 H : 5.97 N : 4.88 C : 50.03 H : 6.18 ~ : 4.75 The following compounds shown in the table below were ob- -~tained in a similar manner to those of Example 1 - Example 7.
TABLE
No. R n m Salt Melting Point( C) -~
1. OCH 2 2 Maleate 150-151.5 - ~ OCH3 2. " 3 2 " 139-141
Elemental analysis: as C20H28N2O5-2C2H2O4 H2O
calculated: C : 50.17 H : 5.97 N : 4.88 C : 50.03 H : 6.18 ~ : 4.75 The following compounds shown in the table below were ob- -~tained in a similar manner to those of Example 1 - Example 7.
TABLE
No. R n m Salt Melting Point( C) -~
1. OCH 2 2 Maleate 150-151.5 - ~ OCH3 2. " 3 2 " 139-141
3. " 2 3 " 156.5-158.5
4. " 3 3 " 146-148
5-- ~ oOCH33 2 3 " 141-143
6. " 3 3 " 1~4.5-145.5
7-~ OCH3 2 3 Hydxochloride 204-206
8. " 3 3 Maleate 154-156
9. ~ 2 3 Hydrochloride 180-183
10. " 3 3 Maleate 146-148 ~. . . . .
: ,. ... . . ... . . . . .
. . .
c ]~
2 3 Maleate 149-150 12. " 3 3 " 122-123.5 13.- ~ F 3 3 Hydrochloride 175-177 14. ~ 2 3 " 178.5-181 15. " 3 3 Maleate 133-134 16. ~ 2 2 1l 127-12~3 N
17. " 2 3 " 138-140 .' :' 15 18. ~ 2 2 " 137-138 N
19. " 2 3 " 158-159 20. " 3 2 " 119-121 21. " 3 3 " 148-149 20 22._ ~ 2 2 " 146-147 ~ N
23. " 3 2 " 112-115 24. " 3 3 " 127-130 25 25.-CH=CH - ~ 2 3 Hydrochloride 198-200 26. " 3 2 Maleate 138-141 27. " 3 3 " 139-140 OCH
30 28.-CH=CH - ~ OCH3 2 2 " 127-128 OCH3 ~ 8 - :
:
,. ,.,.. ,: . .;, ;, . . . . .
, ,,.: . ,, . ,, .. , ' , :
.
i5fl ~
29. " 2 3 .Maleate ~34-135 30. " 3 2 Oxalate 150-151 31. " 3 3 Maleate 108-110 OCH OCH
32. 3 ~ ~ 3 2 2 " 123-124.5 - CH=CH-~ OCH3 33. " 2 3 " 134-135.
34. " 3 2 Oxalate 158-161 ' " ' While the invention has been described in detail and with reference to speciEic embodiments thereo:E, it will be apparent to one skilled in the art that various changes and modification.s can be made therein without departing from the spirit and scope thereoE.
,, .
~ g _ .
. .
' "."'"' ' " ' ~,', ' ,, ',' , " " ' ' ' ' ;
: ,. ... . . ... . . . . .
. . .
c ]~
2 3 Maleate 149-150 12. " 3 3 " 122-123.5 13.- ~ F 3 3 Hydrochloride 175-177 14. ~ 2 3 " 178.5-181 15. " 3 3 Maleate 133-134 16. ~ 2 2 1l 127-12~3 N
17. " 2 3 " 138-140 .' :' 15 18. ~ 2 2 " 137-138 N
19. " 2 3 " 158-159 20. " 3 2 " 119-121 21. " 3 3 " 148-149 20 22._ ~ 2 2 " 146-147 ~ N
23. " 3 2 " 112-115 24. " 3 3 " 127-130 25 25.-CH=CH - ~ 2 3 Hydrochloride 198-200 26. " 3 2 Maleate 138-141 27. " 3 3 " 139-140 OCH
30 28.-CH=CH - ~ OCH3 2 2 " 127-128 OCH3 ~ 8 - :
:
,. ,.,.. ,: . .;, ;, . . . . .
, ,,.: . ,, . ,, .. , ' , :
.
i5fl ~
29. " 2 3 .Maleate ~34-135 30. " 3 2 Oxalate 150-151 31. " 3 3 Maleate 108-110 OCH OCH
32. 3 ~ ~ 3 2 2 " 123-124.5 - CH=CH-~ OCH3 33. " 2 3 " 134-135.
34. " 3 2 Oxalate 158-161 ' " ' While the invention has been described in detail and with reference to speciEic embodiments thereo:E, it will be apparent to one skilled in the art that various changes and modification.s can be made therein without departing from the spirit and scope thereoE.
,, .
~ g _ .
. .
' "."'"' ' " ' ~,', ' ,, ',' , " " ' ' ' ' ;
Claims (6)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for producing a novel piperazine or homopip-erazine-monoalkanol ester represented by the formula:
(I) where when m is 3, R is selected from the group of substit-uents consisting of a phenyl group, a phenyl group substit-uted with a member selected from the group consisting of a lower alkyl group, a lower alkoxy group and a halogen atom, a styryl group which may be substituted with a lower alkoxy group, and a 2-, 3- or 4-pyridyl group which may be substit-uted with a lower alkoxy group; and pharmaceutically acceptable salts thereof; and when m is 2, R is selected from the group of substituents consisting of a styryl group which may be substituted with a lower alkoxy group and a 2-, 3 or 4-pyridyl group which may be substituted with a lower alkoxy group;
and pharmaceutically acceptable salts thereof; which comprises reacting a piperazine- or homopiperazine-mono-alkanol repre-sented by the formula:
(II) wherein n and m are each 2 or 3, or pharmaceutically acceptable salt thereof, with a benzoic acid which may be substituted with a member selected from the group consisting of a lower alkyl group, a lower alkoxy group and a halogen atom, or with a cinnamic acid which may be substituted with a lower alkoxy group to produce a styryl group for R, or with a nicotinic acid which may be substituted with a lower alkoxy group to produce pyridyl group for R; wherein such reaction n is 2 or 3 and m is 2 or 3 in Formula (II).
(I) where when m is 3, R is selected from the group of substit-uents consisting of a phenyl group, a phenyl group substit-uted with a member selected from the group consisting of a lower alkyl group, a lower alkoxy group and a halogen atom, a styryl group which may be substituted with a lower alkoxy group, and a 2-, 3- or 4-pyridyl group which may be substit-uted with a lower alkoxy group; and pharmaceutically acceptable salts thereof; and when m is 2, R is selected from the group of substituents consisting of a styryl group which may be substituted with a lower alkoxy group and a 2-, 3 or 4-pyridyl group which may be substituted with a lower alkoxy group;
and pharmaceutically acceptable salts thereof; which comprises reacting a piperazine- or homopiperazine-mono-alkanol repre-sented by the formula:
(II) wherein n and m are each 2 or 3, or pharmaceutically acceptable salt thereof, with a benzoic acid which may be substituted with a member selected from the group consisting of a lower alkyl group, a lower alkoxy group and a halogen atom, or with a cinnamic acid which may be substituted with a lower alkoxy group to produce a styryl group for R, or with a nicotinic acid which may be substituted with a lower alkoxy group to produce pyridyl group for R; wherein such reaction n is 2 or 3 and m is 2 or 3 in Formula (II).
2. A process of claim 1 for preparing wherein a compound of formula (II) having n=2 and m=2, is reacted with methoxy substituted cinnamic acid of the formula
3. A process of claim 1 for preparing wherein a compound of formula (II) having n=2 and m=3 is reacted with methoxy substituted benzoic acid of the formula
4. A novel piperazine or homopiperazine-monoalkanol ester represented by the formula (I) as defined in claim 1 when prepared by the process of claim 1.
5. A compound of the formula when prepared by the process of claim 2.
6. A compound of the formula when prepared by the process of claim 3.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP47111219A JPS5210877B2 (en) | 1972-11-08 | 1972-11-08 | |
| JP48112289A JPS5224031B2 (en) | 1972-11-08 | 1973-10-08 | |
| JP11229173A JPS5224032B2 (en) | 1973-10-08 | 1973-10-08 | |
| JP11229073A JPS5246235B2 (en) | 1973-10-08 | 1973-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1055492A true CA1055492A (en) | 1979-05-29 |
Family
ID=27469891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA189,574A Expired CA1055492A (en) | 1972-11-08 | 1974-01-07 | Piperazine-and homopiperazine-monoalkanol esters and a process of production thereof |
Country Status (10)
| Country | Link |
|---|---|
| JP (2) | JPS5210877B2 (en) |
| AT (1) | AT333287B (en) |
| BE (1) | BE807031A (en) |
| CA (1) | CA1055492A (en) |
| CH (1) | CH591465A5 (en) |
| DE (1) | DE2355420A1 (en) |
| FR (1) | FR2205515B1 (en) |
| GB (1) | GB1416412A (en) |
| NL (1) | NL7400278A (en) |
| SE (1) | SE398502B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU173380B (en) * | 1977-02-25 | 1979-04-28 | Richter Gedeon Vegyeszet | Process for producing new pyridyl-piperazine derivatives and acid additional salts thereof |
| JPS53144591A (en) * | 1977-05-20 | 1978-12-15 | Asutaabueruke Ag Chem Fuaburii | Process for preparing homopirerazine |
| DE3403778A1 (en) * | 1984-02-03 | 1985-08-08 | Degussa Ag, 6000 Frankfurt | CYANOMETHYL- (2-CYANO-ETHYL) - (3-HYDROXY-PROPYL) -AMINE HIS USE FOR PRODUCING 1- (3-HYDROXY-PROPYL) -1,4-DIAZEPANE AND 1,4-BIS (3- (3rd , 4,5-TRIMETHOXYBENZOYLOXY) -PROPYL) -DIAZEPAN |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2088018A1 (en) * | 1970-05-03 | 1972-01-07 | Rabot Ets David | Vasodilatory, substd nicotinic acid amino ester derivs |
| FR2088019A1 (en) * | 1970-05-08 | 1972-01-07 | Rabot Ets David | Esters of 2 and 6-substituted nicotinic acids - with vasomotor active |
| FR2134121A1 (en) * | 1971-04-20 | 1972-12-08 | Penciolelli Madeleine | Piperazino ethyl phloroglucates prepn - useful as vasodilators |
-
1972
- 1972-11-08 JP JP47111219A patent/JPS5210877B2/ja not_active Expired
-
1973
- 1973-10-08 JP JP48112289A patent/JPS5224031B2/ja not_active Expired
- 1973-11-06 DE DE19732355420 patent/DE2355420A1/en not_active Ceased
- 1973-11-07 FR FR7340568A patent/FR2205515B1/fr not_active Expired
- 1973-11-07 BE BE137507A patent/BE807031A/en unknown
-
1974
- 1974-01-07 CA CA189,574A patent/CA1055492A/en not_active Expired
- 1974-01-07 GB GB58874A patent/GB1416412A/en not_active Expired
- 1974-01-08 SE SE7400215A patent/SE398502B/en unknown
- 1974-01-09 NL NL7400278A patent/NL7400278A/en not_active Application Discontinuation
- 1974-01-09 AT AT13574*#A patent/AT333287B/en not_active IP Right Cessation
- 1974-02-12 CH CH191374A patent/CH591465A5/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2205515B1 (en) | 1978-11-17 |
| CH591465A5 (en) | 1977-09-15 |
| SE7400215L (en) | 1975-04-16 |
| NL7400278A (en) | 1975-04-10 |
| JPS5062983A (en) | 1975-05-29 |
| AT333287B (en) | 1976-11-10 |
| JPS5210877B2 (en) | 1977-03-26 |
| SE398502B (en) | 1977-12-27 |
| DE2355420A1 (en) | 1974-07-04 |
| GB1416412A (en) | 1975-12-03 |
| FR2205515A1 (en) | 1974-05-31 |
| ATA13574A (en) | 1976-03-15 |
| JPS49132088A (en) | 1974-12-18 |
| BE807031A (en) | 1974-03-01 |
| JPS5224031B2 (en) | 1977-06-28 |
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