CA1237128A - Intermediates for preparing substituted 1-piperazine- carboxamides and use thereof - Google Patents
Intermediates for preparing substituted 1-piperazine- carboxamides and use thereofInfo
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- CA1237128A CA1237128A CA000454658A CA454658A CA1237128A CA 1237128 A CA1237128 A CA 1237128A CA 000454658 A CA000454658 A CA 000454658A CA 454658 A CA454658 A CA 454658A CA 1237128 A CA1237128 A CA 1237128A
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Abstract
ABSTRACT
Intermediates which are 1-piperazinecarboxylates or the general formula I
(I) wherein R2, R3, R4, R5 are groups independently selected from hydrogen, lower alkyl having from 1 to 3 carbon atoms and phenyl, R6 is a group selected from hydrogen, F, C1, Br, lower alkoxy having from 1 to 3 carbon atoms and -CF3--groups, R1 represents either an unsubstituted or substitu-ted aryl group with good leaving group properties, suitably a phenyl or a para-nitro-phenyl group-, for producing 1-piperazinecarboxamides of the general formula II
(II) wherein R7 and R8 are groups independently selected from the group of hydrogen, alkyl straight or branched chains having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, aralkyl having from 7 to 9 carbon atoms, alkenyl having from 3 to 10 carbon atoms or R7 and R8 represents together with the adjacent nitrogen atom a 4-7 membered ring such as wherein m = 0, 1, 2, 3, n = 1 or 2, and Ra is a group selected from lower alkyl having from 1 to 3 carbon atoms, hydroxy-loweralkyl having from 2 to 4 carbon atoms and a lower alkanoyl having from 1 to 3 carbon atoms, A process for preparing the carboxamides of formula II by reacting the 1-piperazinecarboxylates of formula I with an amine of formula III
Intermediates which are 1-piperazinecarboxylates or the general formula I
(I) wherein R2, R3, R4, R5 are groups independently selected from hydrogen, lower alkyl having from 1 to 3 carbon atoms and phenyl, R6 is a group selected from hydrogen, F, C1, Br, lower alkoxy having from 1 to 3 carbon atoms and -CF3--groups, R1 represents either an unsubstituted or substitu-ted aryl group with good leaving group properties, suitably a phenyl or a para-nitro-phenyl group-, for producing 1-piperazinecarboxamides of the general formula II
(II) wherein R7 and R8 are groups independently selected from the group of hydrogen, alkyl straight or branched chains having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, aralkyl having from 7 to 9 carbon atoms, alkenyl having from 3 to 10 carbon atoms or R7 and R8 represents together with the adjacent nitrogen atom a 4-7 membered ring such as wherein m = 0, 1, 2, 3, n = 1 or 2, and Ra is a group selected from lower alkyl having from 1 to 3 carbon atoms, hydroxy-loweralkyl having from 2 to 4 carbon atoms and a lower alkanoyl having from 1 to 3 carbon atoms, A process for preparing the carboxamides of formula II by reacting the 1-piperazinecarboxylates of formula I with an amine of formula III
Description
AB Perrosan Intermediates for preparinq substituted l-piperazine-carboxamides and use thereof The present invention relates to new intermediates for preparing N,N,2,3,4,5,6-substituted-1-piperazinecarboxamides and acid addition salts thereof.
Thus the present invention relates to new intermediates which are l-piperazinecarboxylates of formula I
Rl-O- -N N(CH ) CH 1 ~ ~J (I) whe~ein R2, R3, R4, R5 are groups independently selected from hydrogen, lower alkyl having from 1 to 3 carbon atoms and phenyl, R6 is a group selected from hydrogen, F, Cl, Br, lower alkoxy :
having from 1 to 3 carbon atoms and -CF3-groups, R1 represents ei.ther an unsubstituted or substituted aryl group with good leaving group properties, suitably a phenyl or a para-nitro-phenyl group, for producing l-piperazinecarboxamides of the general formula II
R ~ R6 R7 I C N\ N(CH2)3CH ~ (Il) R4R; R6 , ~;Z 37~2~3 wherein R7 and R8 are groups independently selected from the group of hydrogen, alkyl straight or branched chains having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, aralkyl having from 7 to 9 carbon atoms, alkenyl having from 3 to 10 carbon atoms or R7 and R8 represents together with the adjacent nitrogen atom a 4-7-membered ring such as [~ ( CH2 ) m ~ N~ ~ N' ( CH2 ) n I
Ra wherein m = O, 1, 2, 3, n = 1 or 2, and Ra is a group selected from lower alkyl having from 1 to 3 carbon atoms, hydroxy-loweralkyl having from
Thus the present invention relates to new intermediates which are l-piperazinecarboxylates of formula I
Rl-O- -N N(CH ) CH 1 ~ ~J (I) whe~ein R2, R3, R4, R5 are groups independently selected from hydrogen, lower alkyl having from 1 to 3 carbon atoms and phenyl, R6 is a group selected from hydrogen, F, Cl, Br, lower alkoxy :
having from 1 to 3 carbon atoms and -CF3-groups, R1 represents ei.ther an unsubstituted or substituted aryl group with good leaving group properties, suitably a phenyl or a para-nitro-phenyl group, for producing l-piperazinecarboxamides of the general formula II
R ~ R6 R7 I C N\ N(CH2)3CH ~ (Il) R4R; R6 , ~;Z 37~2~3 wherein R7 and R8 are groups independently selected from the group of hydrogen, alkyl straight or branched chains having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, aralkyl having from 7 to 9 carbon atoms, alkenyl having from 3 to 10 carbon atoms or R7 and R8 represents together with the adjacent nitrogen atom a 4-7-membered ring such as [~ ( CH2 ) m ~ N~ ~ N' ( CH2 ) n I
Ra wherein m = O, 1, 2, 3, n = 1 or 2, and Ra is a group selected from lower alkyl having from 1 to 3 carbon atoms, hydroxy-loweralkyl having from
2 to 4 carbon atoms and a lower alkanoyl having from 1 to 3 carbon atoms. R2, ~3, R~, R5 and R6 are as defined above.
Said compounds of formula II have a therapeutic activity in the central nervous system having a new pharmacological mode of action not seen in any compound described earlier. If given for example to male mice made aggressive by isolation they induce a potent and longlasting inhibition of this aggressive behaviour without causing any ataxia or catalepsy. In contrast to known neuroleptics the new compo~nds of formula II do not inhibit apomorphine or amphetamine induced stereotypies. The compounds decrease exploratory behaviour and have influence on condition avoidance response. These and other findings suggest that the compounds have antipsychotic properties with a low incidence of unwanted side-effects, e.g. e~trapyramidal side-effects. The compounds induce behavioural effects in monkeys which are similar to what is seen after antidepressants. This means that the compounds may be useful in the treatment of depressions. Furthermore, the new compounds show valuable analgesic properties, which are not reversed by naloxone.
Contrary to morphine the compounds have not been found to create physical dependence on chronic administration.
~23~1L2~
The antianxiety and the protecting effect against induced s-tress shown by the compounds of formula II may be of value in the treatment o psychosomatic disorders and of ulcus in man.
Based on these findings it is concluded that the com-pounds of formula II will be useful in the treatment of mental disorders in man as well as in animals although their pharmacolog-ical activities are different from those of the neuroleptics, antidepressants and anxiolytics now used in the clinic. The pro-file of action of the compounds of formula II suggests an influence on limbic, hypothalamic and pituital areas of the brain.
The compounds of formula II seem to be useful in the treatment of aggressive behaviour in animals, especially in pigs, in promoting without bursts of aggression the development of a natural hierarchy in groups of animals and in calming of anxious and stressed animals.
The compounds of formula II are described in our British patent 2,037,745. Compounds of the general formula I are described in our European patent application 80,922 (published June 8, 1983) and are useful in human and veterinary medicine for treatment of mental disorders such as aggression and psychosis in mammals.
According to the present invention it has been found that compounds of the general formula I can be used as intermedi-ates for the preparation of the compounds of the general formula II.
~ ~ l - 3 -
Said compounds of formula II have a therapeutic activity in the central nervous system having a new pharmacological mode of action not seen in any compound described earlier. If given for example to male mice made aggressive by isolation they induce a potent and longlasting inhibition of this aggressive behaviour without causing any ataxia or catalepsy. In contrast to known neuroleptics the new compo~nds of formula II do not inhibit apomorphine or amphetamine induced stereotypies. The compounds decrease exploratory behaviour and have influence on condition avoidance response. These and other findings suggest that the compounds have antipsychotic properties with a low incidence of unwanted side-effects, e.g. e~trapyramidal side-effects. The compounds induce behavioural effects in monkeys which are similar to what is seen after antidepressants. This means that the compounds may be useful in the treatment of depressions. Furthermore, the new compounds show valuable analgesic properties, which are not reversed by naloxone.
Contrary to morphine the compounds have not been found to create physical dependence on chronic administration.
~23~1L2~
The antianxiety and the protecting effect against induced s-tress shown by the compounds of formula II may be of value in the treatment o psychosomatic disorders and of ulcus in man.
Based on these findings it is concluded that the com-pounds of formula II will be useful in the treatment of mental disorders in man as well as in animals although their pharmacolog-ical activities are different from those of the neuroleptics, antidepressants and anxiolytics now used in the clinic. The pro-file of action of the compounds of formula II suggests an influence on limbic, hypothalamic and pituital areas of the brain.
The compounds of formula II seem to be useful in the treatment of aggressive behaviour in animals, especially in pigs, in promoting without bursts of aggression the development of a natural hierarchy in groups of animals and in calming of anxious and stressed animals.
The compounds of formula II are described in our British patent 2,037,745. Compounds of the general formula I are described in our European patent application 80,922 (published June 8, 1983) and are useful in human and veterinary medicine for treatment of mental disorders such as aggression and psychosis in mammals.
According to the present invention it has been found that compounds of the general formula I can be used as intermedi-ates for the preparation of the compounds of the general formula II.
~ ~ l - 3 -
3~7~LZB
The compounds of general formula II are obtained by reacting l-piperazinecarboxylates o~ formula I wi-th an amine of the general formula III
R7 - NH (III) wherein R7 and R8 are as defined above.
~ ~ - 3a -~23~Z~ 4 Thus, the compound of formula I is reac-ted with the amine of formula III in a suitable solvent, e.g. the amine in excess or an aromatic hydrocarbon such as benzene, toluene or xylene and the like or in a lower allcanol such as ethanol, propanol or butanol, i~ desired, in the presence of an appropriate base, e.g. an suitable alkali metal alkoxide to yield the compound of formula II. Heating may facilitate the reaction.
The present invention relates to the use of the compounds of formula I for preparing a compound of formula II.
The following examples are intended to illustrate the intermediates of the present invention and their use in preparing compounds of formula II without limiting the scope thereof.
The compounds of general formula II are obtained by reacting l-piperazinecarboxylates o~ formula I wi-th an amine of the general formula III
R7 - NH (III) wherein R7 and R8 are as defined above.
~ ~ - 3a -~23~Z~ 4 Thus, the compound of formula I is reac-ted with the amine of formula III in a suitable solvent, e.g. the amine in excess or an aromatic hydrocarbon such as benzene, toluene or xylene and the like or in a lower allcanol such as ethanol, propanol or butanol, i~ desired, in the presence of an appropriate base, e.g. an suitable alkali metal alkoxide to yield the compound of formula II. Heating may facilitate the reaction.
The present invention relates to the use of the compounds of formula I for preparing a compound of formula II.
The following examples are intended to illustrate the intermediates of the present invention and their use in preparing compounds of formula II without limiting the scope thereof.
4-~4,4-bis(~-fluoro~henyl)-buty~ -l-carbo-l~-nitrophenoxy)-~iperazine 33.0 g (0.1 mole) of 1-[4,4-bis(p-fluorophenyl~-butyl]-piperazine was dissolved in 500 ml ether. 20 g MgO in 250 ml H2O was added.
The mixture was stirred vigorously at 0C and 20.0 g (0.1 mole) of p-nitrophenyl-chloroformate was added during 1 h. The mixture was allowed to reach room temperature, filtered and the phases were separated. The organic layer was extracted with lN NaOH and saturated NaCl-solution, dried and the solvents evaporated. Ligroin was added and 29.1 g of 4-~4,4-bis(p-fluorophenyl)butyl~-1-carbo-(p-nitrophenoxy)--piperazine was collected by filtration. Melting point after recrystallization from ethanol/ethyl acetate 112-13C.
N-But~yl-4-~4-bis(~-fluorophenyl)butyl]-l-~i~erazinecarboxa-mide hydrochlori~e 3.0 g (6.1 mmole) of 4-r4,4-bis(p-fluorophenyl)-butyl~-1-carbo--(p-nitrophenoxy)-piperazine was dissolved in 30 ml butylamine, and ~;~37~8 5 stirred for 2 h at room tempera-ture. The mlxture was partitioned between H2O and cyclohexane-ether. The organic layer was washed with NaOH and H2O. After drying the solvent was evaporated under reriuced pressure. The residue was dlssolved in ethanol-ether and the hydrochloride was precipitated with ethanolic HCl. The solid was collected by filtration and recrystallised from ethanol-ether to give 2.0 g of N-butyl-4-[4,4-bis-p-fluorophenyl)butyl]-1--piperazinecarboxamide hydrochloride. Melting point 185-187C.
The title compound was identical to that previously described in British patent 2.037.745.
The reaction of ~-~4,4-bis(p-fluorophenyl)-butyl~-1-carbophenoxy--piperazine with butylamine requires somewhat higher reaction temperatures and longer reaction time.
l-(Morpholinocarbonyl)-4-r4Ld-bls(p-fluorophenyl)butyll-pipera~ine oxalate 4.8 g (9.7 mmole) of 4-r4,4-bis(p-fluorophenyl)-butyl~-1-carbo--(p-nitrophenoxy)-piperazine and excess morpholine (~3 eq.) were dissolved in 30 ml dry toluene, and refluxed until TLC indicated the disappearance of all starting material. The reaction mixture was cooled and extracted with 1 x NaOH, 3 x NaCl solution. After drying with Na2SO4 and evaporation of the solvents the residue was dissolved in ether and precipitated with excess oxalic acid in ether.
After filtration most of the material was dissolved in EtOH/H20 (~200 ml). Undissolved material was filtered off, and subsequent evaporation of most of the ethanol yielded 3.2 g of l-(morpholino-carbonyl)-4-r4,4-bis(p-fluorophenyl)butyl]-piperazine oxalate.
Melting point 213-15C.
In the same manner the following compounds of formula II can be prepared by reacting the appropriate l-piperazinecarboxylate of formula I with the appropriate amine of the formula III:
~;~37 ILZ~
N-Ethyl-4-~4,4-bis(p-~luorophenyi)butyl -1-piperazinecarboxamide hydrochloride, melting point 177-78C.
N-Methyl-4-'4,4-bis(p-fluorophenyl)bu-tyll-1-piperazinecarboxamide, melting point 160-62C.
trans-2,5-Dimethyl-N-methyl-4-~4,4-bis(p-fluorophenyl)butyl~--l-piperazinecarboxamide oxalate, melting point 153-55C.
4-r4,4-bis(p-Fluorophenyl)butyl~ -l-piperazinecarboxamide hydrochloride, melting point 195-97C.
N-Fthyl-4- 4,4-bis(phenyl)butyl! -l-piperazinecarboxamide hydrochloride, melting point 191-92C.
In the same manner compounds having the following formula can be prepared:
R ~ ~F
¦ 8 R7 - N - C - N N ~ CH2CH2CH2CH ~
, .
~.237~ 7 R7 R8 R2 R5 C S~lt CI~3 CH3 H H 129-31 HCl CH3 C2H5 H H 152-53 HCl C2H5 2 5 ~ 203-05 oxal~te C2H5 H CH3 ) CH3 ) 184-86 HCl 3 7 H H H 190-92 HCl iso-C3H7 H H H 206-08 HCl iso-C H H CH3b) CH3b) 184-86 HCl cyclo-C3H5 H H H 192-94 HCl cyclo-C3H5 H CH3 ) CH3 ) 172-75 HCl tert-C4Hg H H H 191-93 HCl CH2-cyclo-C3H5 H H H 196-98 HCl n C5Hll H H H 172-74 HCl cyclo-C H H H H 172-73 HClC) n C8H17 H H H 187-89 HCl CH2=CHCH2 H H H 187-89 HCl CH -C H H H H 185-87 HCl 2 2 6 5 H H H 139-41 HCl ., .
.~
~L~23'~ 8 R7 -~ R8 R2 R5 C Salt I H H 202-03 oxalate ~, \
H H 172-74 HCl O H H 134-35 HCI ) /~ .
OH H H 203-05 ca 1.5 oxalate (decomp) NH H H 187-88 2 fumarate N-CH3 H H >250 2HCl N ~ CH3 H H 210-12 HCl a) Melting points are uncorrected b) trans-2,5~dimethyl --c) Hydrate (about one H2O)
The mixture was stirred vigorously at 0C and 20.0 g (0.1 mole) of p-nitrophenyl-chloroformate was added during 1 h. The mixture was allowed to reach room temperature, filtered and the phases were separated. The organic layer was extracted with lN NaOH and saturated NaCl-solution, dried and the solvents evaporated. Ligroin was added and 29.1 g of 4-~4,4-bis(p-fluorophenyl)butyl~-1-carbo-(p-nitrophenoxy)--piperazine was collected by filtration. Melting point after recrystallization from ethanol/ethyl acetate 112-13C.
N-But~yl-4-~4-bis(~-fluorophenyl)butyl]-l-~i~erazinecarboxa-mide hydrochlori~e 3.0 g (6.1 mmole) of 4-r4,4-bis(p-fluorophenyl)-butyl~-1-carbo--(p-nitrophenoxy)-piperazine was dissolved in 30 ml butylamine, and ~;~37~8 5 stirred for 2 h at room tempera-ture. The mlxture was partitioned between H2O and cyclohexane-ether. The organic layer was washed with NaOH and H2O. After drying the solvent was evaporated under reriuced pressure. The residue was dlssolved in ethanol-ether and the hydrochloride was precipitated with ethanolic HCl. The solid was collected by filtration and recrystallised from ethanol-ether to give 2.0 g of N-butyl-4-[4,4-bis-p-fluorophenyl)butyl]-1--piperazinecarboxamide hydrochloride. Melting point 185-187C.
The title compound was identical to that previously described in British patent 2.037.745.
The reaction of ~-~4,4-bis(p-fluorophenyl)-butyl~-1-carbophenoxy--piperazine with butylamine requires somewhat higher reaction temperatures and longer reaction time.
l-(Morpholinocarbonyl)-4-r4Ld-bls(p-fluorophenyl)butyll-pipera~ine oxalate 4.8 g (9.7 mmole) of 4-r4,4-bis(p-fluorophenyl)-butyl~-1-carbo--(p-nitrophenoxy)-piperazine and excess morpholine (~3 eq.) were dissolved in 30 ml dry toluene, and refluxed until TLC indicated the disappearance of all starting material. The reaction mixture was cooled and extracted with 1 x NaOH, 3 x NaCl solution. After drying with Na2SO4 and evaporation of the solvents the residue was dissolved in ether and precipitated with excess oxalic acid in ether.
After filtration most of the material was dissolved in EtOH/H20 (~200 ml). Undissolved material was filtered off, and subsequent evaporation of most of the ethanol yielded 3.2 g of l-(morpholino-carbonyl)-4-r4,4-bis(p-fluorophenyl)butyl]-piperazine oxalate.
Melting point 213-15C.
In the same manner the following compounds of formula II can be prepared by reacting the appropriate l-piperazinecarboxylate of formula I with the appropriate amine of the formula III:
~;~37 ILZ~
N-Ethyl-4-~4,4-bis(p-~luorophenyi)butyl -1-piperazinecarboxamide hydrochloride, melting point 177-78C.
N-Methyl-4-'4,4-bis(p-fluorophenyl)bu-tyll-1-piperazinecarboxamide, melting point 160-62C.
trans-2,5-Dimethyl-N-methyl-4-~4,4-bis(p-fluorophenyl)butyl~--l-piperazinecarboxamide oxalate, melting point 153-55C.
4-r4,4-bis(p-Fluorophenyl)butyl~ -l-piperazinecarboxamide hydrochloride, melting point 195-97C.
N-Fthyl-4- 4,4-bis(phenyl)butyl! -l-piperazinecarboxamide hydrochloride, melting point 191-92C.
In the same manner compounds having the following formula can be prepared:
R ~ ~F
¦ 8 R7 - N - C - N N ~ CH2CH2CH2CH ~
, .
~.237~ 7 R7 R8 R2 R5 C S~lt CI~3 CH3 H H 129-31 HCl CH3 C2H5 H H 152-53 HCl C2H5 2 5 ~ 203-05 oxal~te C2H5 H CH3 ) CH3 ) 184-86 HCl 3 7 H H H 190-92 HCl iso-C3H7 H H H 206-08 HCl iso-C H H CH3b) CH3b) 184-86 HCl cyclo-C3H5 H H H 192-94 HCl cyclo-C3H5 H CH3 ) CH3 ) 172-75 HCl tert-C4Hg H H H 191-93 HCl CH2-cyclo-C3H5 H H H 196-98 HCl n C5Hll H H H 172-74 HCl cyclo-C H H H H 172-73 HClC) n C8H17 H H H 187-89 HCl CH2=CHCH2 H H H 187-89 HCl CH -C H H H H 185-87 HCl 2 2 6 5 H H H 139-41 HCl ., .
.~
~L~23'~ 8 R7 -~ R8 R2 R5 C Salt I H H 202-03 oxalate ~, \
H H 172-74 HCl O H H 134-35 HCI ) /~ .
OH H H 203-05 ca 1.5 oxalate (decomp) NH H H 187-88 2 fumarate N-CH3 H H >250 2HCl N ~ CH3 H H 210-12 HCl a) Melting points are uncorrected b) trans-2,5~dimethyl --c) Hydrate (about one H2O)
Claims (6)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for producing 1-piperazinecarboxamides of the general formula II
(II) wherein R2, R3, R4, R5 are groups independently selected from hydrogen, lower alkyl having from 1 to 3 carbon atoms and phenyl, R6 is a group selected from hydrogen, F, Cl, Br, lower alkoxy having from 1 to 3 carbon atoms and -CF3-groups, R7 and R8 are groups independently selected from the group of hydrogen, alkyl straight or branched chains having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, aralkyl having from 7 to 9 carbon atoms, alkenyl having from 3 to 10 carbon atoms or R7 and R8 represents together with the adjacent nitrogen atom a 4-7-membered ring, chosen from wherein m = O, 1, 2, 3, n = 1 or 2, and Ra is a group selected from lower alkyl having from 1 to 3 carbon atoms, hydroxy-lower-alkyl having from 2 to 4 carbon atoms and a lower alkanoyl having from 1 to 3 carbon atoms, characterized by reacting a 1-piper-azinecarboxylate of formula I
(I) wherein R2, R3, R4, R5 and R6 are as defined above, R1 represents either an unsubstituted or substituted aryl group with good leaving group properties, with an amine of the general formula III
(III) wherein R7 and R8 are as defined above, in an inert solvent.
(II) wherein R2, R3, R4, R5 are groups independently selected from hydrogen, lower alkyl having from 1 to 3 carbon atoms and phenyl, R6 is a group selected from hydrogen, F, Cl, Br, lower alkoxy having from 1 to 3 carbon atoms and -CF3-groups, R7 and R8 are groups independently selected from the group of hydrogen, alkyl straight or branched chains having from 1 to 10 carbon atoms, cycloalkyl having from 3 to 8 carbon atoms, aralkyl having from 7 to 9 carbon atoms, alkenyl having from 3 to 10 carbon atoms or R7 and R8 represents together with the adjacent nitrogen atom a 4-7-membered ring, chosen from wherein m = O, 1, 2, 3, n = 1 or 2, and Ra is a group selected from lower alkyl having from 1 to 3 carbon atoms, hydroxy-lower-alkyl having from 2 to 4 carbon atoms and a lower alkanoyl having from 1 to 3 carbon atoms, characterized by reacting a 1-piper-azinecarboxylate of formula I
(I) wherein R2, R3, R4, R5 and R6 are as defined above, R1 represents either an unsubstituted or substituted aryl group with good leaving group properties, with an amine of the general formula III
(III) wherein R7 and R8 are as defined above, in an inert solvent.
2. A process according to claim 1 wherein the group R1 is a phenyl or para-nitro-phenyl group.
3. A process according to claim 1 wherein a base is also present.
4. A process according to claim 3 wherein the base is an alkali metal alkoxide.
5. A process according to claim 1 wherein the solvent is chosen from an aromatic hydrocarbon or a lower alkanol.
6. A process according to claim 1 wherein the solvent is chosen from benzene, toluene, xylene, ethanol, propanol or butanol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8302886-0 | 1983-05-20 | ||
| SE8302886A SE8302886D0 (en) | 1983-05-20 | 1983-05-20 | INTERMEDIATES FOR PREPARING SUBSTITUTED 1-PIPERAZINE CARBOXAMIDES AND CARBOTHIOAMIDES AND USE THEREOF |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1237128A true CA1237128A (en) | 1988-05-24 |
Family
ID=20351277
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000454658A Expired CA1237128A (en) | 1983-05-20 | 1984-05-18 | Intermediates for preparing substituted 1-piperazine- carboxamides and use thereof |
Country Status (4)
| Country | Link |
|---|---|
| CA (1) | CA1237128A (en) |
| DK (1) | DK159312C (en) |
| FI (1) | FI86179C (en) |
| SE (1) | SE8302886D0 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5574031A (en) * | 1992-07-31 | 1996-11-12 | Pharmacia Aktiebolag | Piperazine carboxamides |
-
1983
- 1983-05-20 SE SE8302886A patent/SE8302886D0/en unknown
-
1984
- 1984-05-17 DK DK246384A patent/DK159312C/en not_active IP Right Cessation
- 1984-05-18 CA CA000454658A patent/CA1237128A/en not_active Expired
- 1984-05-18 FI FI842011A patent/FI86179C/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5574031A (en) * | 1992-07-31 | 1996-11-12 | Pharmacia Aktiebolag | Piperazine carboxamides |
Also Published As
| Publication number | Publication date |
|---|---|
| FI86179B (en) | 1992-04-15 |
| DK246384D0 (en) | 1984-05-17 |
| DK246384A (en) | 1984-11-21 |
| FI86179C (en) | 1992-07-27 |
| SE8302886D0 (en) | 1983-05-20 |
| DK159312B (en) | 1990-10-01 |
| DK159312C (en) | 1991-03-25 |
| FI842011A0 (en) | 1984-05-18 |
| FI842011A (en) | 1984-11-21 |
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