CA1055491A - Process for the manufacture of benzodiazepine derivatives - Google Patents
Process for the manufacture of benzodiazepine derivativesInfo
- Publication number
- CA1055491A CA1055491A CA222,888A CA222888A CA1055491A CA 1055491 A CA1055491 A CA 1055491A CA 222888 A CA222888 A CA 222888A CA 1055491 A CA1055491 A CA 1055491A
- Authority
- CA
- Canada
- Prior art keywords
- signifies
- compound
- general formula
- formula
- defined above
- 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.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/28—Preparation including building-up the benzodiazepine skeleton from compounds containing no hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
Abstract Benzodiazepine derivatives of formula I
wherein R signifies hydrogen or alkyl, R1 signifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, halophenyl or pyridyl, and 4-oxides thereof are prepared by a novel process which comprises reacting a benzophenone of the general formula II
wherein R, R1 and R2 are as defined above with a nitroacetic acid halide, reducing the abtained nitro-acetyl compound of the general formula III
wherein R, R1 and R2 are as defined above to the corresponding hydroxylamine or amine derivative and cyclizing the product thus obtained.
Benzodiazepines of formula I and 4-oxides thereof are known compounds which are known to be useful as sedatives, anticonvulsants and muscle relaxants.
wherein R signifies hydrogen or alkyl, R1 signifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, halophenyl or pyridyl, and 4-oxides thereof are prepared by a novel process which comprises reacting a benzophenone of the general formula II
wherein R, R1 and R2 are as defined above with a nitroacetic acid halide, reducing the abtained nitro-acetyl compound of the general formula III
wherein R, R1 and R2 are as defined above to the corresponding hydroxylamine or amine derivative and cyclizing the product thus obtained.
Benzodiazepines of formula I and 4-oxides thereof are known compounds which are known to be useful as sedatives, anticonvulsants and muscle relaxants.
Description
1~55g~9~
The present invention relates to an improved process for the manufacture of benzodiazepine derivatives of the general formula ~ ~ - CO
Rl N
wherein R signifies hydrogen or alkyl with up to 7 carbon atoms, Rl s;.gnifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, and 4-oxides thereof.
The expression "halogen" includes the four halogens fluorine, chlorine, bromine and iodine.
In a preferred embodiment of the process in accordance with the invention, Rl signifies halcgen, preferably chlorin~, ., ~ .
': ', ~ ., . :' , .
~5549~
Especially preferred is the manufacture of 7-chloro-1,3-dihydro- - -l-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.
This invention relates to an improved process for the manufacture of benzodiazepine derivatives of the general formula R
~ N - C ~ I :
Rl C = N
wherein R signi~ies hydrogen or alkyl with up to 7 carbon atoms, R
signifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, and 4-oxides thereof by cyclization a compound of the general formula R
~/N-co-cH2-NH-R3 ' ' l C=O IV
R2 :1 wherein R, Rl and R2 are as defined above and R3 signifies hydrogen or :~.
hydroxy the improvement which comprises preparing the compound of formula IV by reacting a benzophenone of the general formula R
NH
Rl ~ C=O II
R2 ~. .
wherein R, Rl and R2 are as definad above with a nitroacetic acid halide and reducing the obtained nitroacetyl compound of the general formula ~ r - 3 - ~
,, : .
l~S5491 Rl ~ C=O III
wherein R, Rl and R2 are as defined above, either a) wi~h about 6 g. atom of zinc per mol. of compound III in order to obtain a compound of ~ormula IV, wherein R3 is hydroxy, or b) with about 10 g. atom of zinc per mol. of compound III or catalytically in order to obtain a compound of formula IV, wherein R3 is hydrogen.
:.
': '' ,.
: :~ .
_.. .
~' ~.;~
,: , ' ' ,.,.. : :
lC~SS~91 The reaction Or a compound o~ the general fQrmula II
with the acid halide is preferably carried out in an inert organic solvent(such as hydrocarbons, e.g. benzene, toluene and the liken chlorinated hydrocarbons such as chloroform, methylene chloride and the like, ethers such as dioxane and the like)and at temperatures from -5 to 50C.
It is expedient to use nitroacetyl chloride as the nitroacetic acid hali~e. ~his nikroacetyl chloride can be obtained expediently by the reaction of nitroacetic acid with phosphoru~ pentachloride~ whereby the mixture o~ nitroacetyl chloride and phosphorus oxyehloride can be used directly for the acylation.
~he reduction of a compound of the form~la III can be carried out~ e.g~ with zinc9 expedien~ly in acidic or neutral medium and at temperatureR rrom -20~ to 100C. Depending on the reaction condition~, i.e, the reaction time or the amount of acid and zinc used, there is obtained a hydro~lamine deri~ativ~ of the general formula 0-CH2-NH~H
Rl ~ ~ IV~
wherein R~ Rl and R2 are as de~ined above ,:
or an amine of the general formula ...
. .
i;S4~l H2-NH4~ ~Vb wherein R, Rl and R2 are as defined above.
Ilfq Amines of the formula ~ can also be obtained from the corres-ponding nitro derivatives o~ the ~ormula III by catalytic reduction, e.g. with palladiumJ platinum and the like.
The reduction of a compound of the formula III to a hydroxylamine or amine derivative is expediently effected in a solvent such as hydrocarbons, e.g. benzene, toluene, chlorinated hydrocarbons, e.g. methylene chloride, alcohols such as methanol, ethanol, ethers, glacial acetic acid, aqueous acetic acid (either alone or in admixture with other solvents, e.g. the solvents ~ust mentioned).
rme cyclisation of a hydroxylamine or amlne derivative can be ef~ecked in acidic or alkaline medium in a known manner.
~:
Compounds of the formula I~ and N~can be cyclised without isolation o~ same ~rom the reaction mixture.
~ .
Benzodiazepines of formula I and l~-oxides thereof are known compounds which are known to be userul as sedatlves, anticonvulsants and muscle relaxants.
!
.
~5549~
The following Examples illustrate the process in accor-dance with the invention. All temperatures are given in C.
Example 10.5 g (0.1 mol) of nitroacetic acid are suspended in 50 ml of dry chloroform and 23 g (0.11 mol) of phosphorus pentachloride are added at -20. The reaction mixture is stirred for 30 minutes at -20 to -10. The clear solution so-obtained~ together with 200 ml of a 15 ~ sodium carbonate solution is added dropwise at 2-5 to a strongly stirred solution of 11.6 g (0.05 mol) of 2-amino-5-chlorobenzophenone in 100 ml of chloroform. By a rapid addition of the acid chloride mixture, it is achieved that at no point in time does the reaction mixture react alkaline. After effecting the addition, the mixture is stirred at 5-10 for a further 15 ~5 minuteæ. The chloroform phase is then separated, washed with water, drled over sodium sulphate and thoroughly evaporated (~ 30 ). The orystalline residue is suspended in ether and filtered off under suction to give 2'-benzoyl-4'-chloro-2-nitroa¢etanllide of meltlng point 163-166 (decomp. and conversion into 6-chloro-~-nitro-4-phenylcarbostyril).
4 g of zinc dust are introduced in one portion into a solution of 3.2 g (0.01 mol) of 2'-benzoyl-4'-chloro-2-nitro-acetanillde in 100 ml of methylene chloride and 4 ml of .
.. ...
.. . . . .. . . . . .
~SS49~
glacial acetic acid with stirring under nitrogen. The temperature increase results in a vigorous reflux of the solvent. After cessation of the exothermal reaction, the mixture is stirred for a further 10 minutes and made alkaline with dilute ammonia. The methylene chloride phase is dried over anhydrous sodium sulphate, filtered and evaporated in vacuo. The residue is taken up in ether and there crystallises
The present invention relates to an improved process for the manufacture of benzodiazepine derivatives of the general formula ~ ~ - CO
Rl N
wherein R signifies hydrogen or alkyl with up to 7 carbon atoms, Rl s;.gnifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, and 4-oxides thereof.
The expression "halogen" includes the four halogens fluorine, chlorine, bromine and iodine.
In a preferred embodiment of the process in accordance with the invention, Rl signifies halcgen, preferably chlorin~, ., ~ .
': ', ~ ., . :' , .
~5549~
Especially preferred is the manufacture of 7-chloro-1,3-dihydro- - -l-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.
This invention relates to an improved process for the manufacture of benzodiazepine derivatives of the general formula R
~ N - C ~ I :
Rl C = N
wherein R signi~ies hydrogen or alkyl with up to 7 carbon atoms, R
signifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, and 4-oxides thereof by cyclization a compound of the general formula R
~/N-co-cH2-NH-R3 ' ' l C=O IV
R2 :1 wherein R, Rl and R2 are as defined above and R3 signifies hydrogen or :~.
hydroxy the improvement which comprises preparing the compound of formula IV by reacting a benzophenone of the general formula R
NH
Rl ~ C=O II
R2 ~. .
wherein R, Rl and R2 are as definad above with a nitroacetic acid halide and reducing the obtained nitroacetyl compound of the general formula ~ r - 3 - ~
,, : .
l~S5491 Rl ~ C=O III
wherein R, Rl and R2 are as defined above, either a) wi~h about 6 g. atom of zinc per mol. of compound III in order to obtain a compound of ~ormula IV, wherein R3 is hydroxy, or b) with about 10 g. atom of zinc per mol. of compound III or catalytically in order to obtain a compound of formula IV, wherein R3 is hydrogen.
:.
': '' ,.
: :~ .
_.. .
~' ~.;~
,: , ' ' ,.,.. : :
lC~SS~91 The reaction Or a compound o~ the general fQrmula II
with the acid halide is preferably carried out in an inert organic solvent(such as hydrocarbons, e.g. benzene, toluene and the liken chlorinated hydrocarbons such as chloroform, methylene chloride and the like, ethers such as dioxane and the like)and at temperatures from -5 to 50C.
It is expedient to use nitroacetyl chloride as the nitroacetic acid hali~e. ~his nikroacetyl chloride can be obtained expediently by the reaction of nitroacetic acid with phosphoru~ pentachloride~ whereby the mixture o~ nitroacetyl chloride and phosphorus oxyehloride can be used directly for the acylation.
~he reduction of a compound of the form~la III can be carried out~ e.g~ with zinc9 expedien~ly in acidic or neutral medium and at temperatureR rrom -20~ to 100C. Depending on the reaction condition~, i.e, the reaction time or the amount of acid and zinc used, there is obtained a hydro~lamine deri~ativ~ of the general formula 0-CH2-NH~H
Rl ~ ~ IV~
wherein R~ Rl and R2 are as de~ined above ,:
or an amine of the general formula ...
. .
i;S4~l H2-NH4~ ~Vb wherein R, Rl and R2 are as defined above.
Ilfq Amines of the formula ~ can also be obtained from the corres-ponding nitro derivatives o~ the ~ormula III by catalytic reduction, e.g. with palladiumJ platinum and the like.
The reduction of a compound of the formula III to a hydroxylamine or amine derivative is expediently effected in a solvent such as hydrocarbons, e.g. benzene, toluene, chlorinated hydrocarbons, e.g. methylene chloride, alcohols such as methanol, ethanol, ethers, glacial acetic acid, aqueous acetic acid (either alone or in admixture with other solvents, e.g. the solvents ~ust mentioned).
rme cyclisation of a hydroxylamine or amlne derivative can be ef~ecked in acidic or alkaline medium in a known manner.
~:
Compounds of the formula I~ and N~can be cyclised without isolation o~ same ~rom the reaction mixture.
~ .
Benzodiazepines of formula I and l~-oxides thereof are known compounds which are known to be userul as sedatlves, anticonvulsants and muscle relaxants.
!
.
~5549~
The following Examples illustrate the process in accor-dance with the invention. All temperatures are given in C.
Example 10.5 g (0.1 mol) of nitroacetic acid are suspended in 50 ml of dry chloroform and 23 g (0.11 mol) of phosphorus pentachloride are added at -20. The reaction mixture is stirred for 30 minutes at -20 to -10. The clear solution so-obtained~ together with 200 ml of a 15 ~ sodium carbonate solution is added dropwise at 2-5 to a strongly stirred solution of 11.6 g (0.05 mol) of 2-amino-5-chlorobenzophenone in 100 ml of chloroform. By a rapid addition of the acid chloride mixture, it is achieved that at no point in time does the reaction mixture react alkaline. After effecting the addition, the mixture is stirred at 5-10 for a further 15 ~5 minuteæ. The chloroform phase is then separated, washed with water, drled over sodium sulphate and thoroughly evaporated (~ 30 ). The orystalline residue is suspended in ether and filtered off under suction to give 2'-benzoyl-4'-chloro-2-nitroa¢etanllide of meltlng point 163-166 (decomp. and conversion into 6-chloro-~-nitro-4-phenylcarbostyril).
4 g of zinc dust are introduced in one portion into a solution of 3.2 g (0.01 mol) of 2'-benzoyl-4'-chloro-2-nitro-acetanillde in 100 ml of methylene chloride and 4 ml of .
.. ...
.. . . . .. . . . . .
~SS49~
glacial acetic acid with stirring under nitrogen. The temperature increase results in a vigorous reflux of the solvent. After cessation of the exothermal reaction, the mixture is stirred for a further 10 minutes and made alkaline with dilute ammonia. The methylene chloride phase is dried over anhydrous sodium sulphate, filtered and evaporated in vacuo. The residue is taken up in ether and there crystallises
2'-benzoyl-4'-chloro-2-hydroxylaminoace~anilide which, after recrystallisation from alcohol, melts at 125-128. This product can be converted, for example by t~eatment with alcoholic hydro-chloric acid, into 7-chloro-1,3-dihydro-5-phenyl-2H-l,~-benzo-diazepin-2-one 4-oxide of melting point 231-233.
Example 2 . .
The nitroacetic acid chloride is prepared from 10.5 g of nitroacetic acid and 23 g of phosphorus pentachloride accord-ing to the proceduro described in Example 1. This acid chloride is added dropwise at 5-10, together with 200 ml of a 15 % soda solution, ~o a strongly stirred solution o~ 12.3 g ~0.05 mol) of 5-chloro-2-methylaminobenzophenone in 50 ml of chloro~orm.
At the end of the addition, the mixture is stirred for a ~urther 20 minutes at 5-10. The chloroform phase is separated, washed with water, dried over sodium sulphate and evaporated in vacuo at 30. The residue is crystallized from ether. After recrystallisation from methylene chloride/hexane, ~J
" . . .............. , "
. .. ... , ., . , . : .
. . . . .. .. .
~La35549~
there is obtained 2'-benzoyl-4'-chloro-N-methyl-2 nitro acetanilide of melting point 120-123 (decomp. and conversion into 6-chloro-1-methyl-3-nitro-4-phenylcarbostyril of mel~ing point 212-214).
1 ml of glacial acetic acid and 2 g of zinc dust are added to a solution of lg of 2'-benzoyl-4'-chloro-N-methyl-2-nitroacetanilide in 15 ml of me~hylene chloride. After the exothermal reaction, the mixture is stirred at room temperature for a further 15 minutes. After the addition of 5 ml of conc.
ammonia, the reaction mixture is partitioned between Nater and ether. The ether phase is extracted 3 x with 2-n hydrochloric acid. The ~xtracts are washed with ether and are made alkaline by addition of ammonia. The liberated bases are extracted with methylene chlorid0. The extracts are dried over sodium sulphate and evaporated to yield a crude product~ By chromatography on 15 g of silica gel with 10 % ethyl acetate in methylene chloride -and crystallisation from ether/hexane, there is obtained 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one of m.p.
130-13~.
- ;-, q~ ' .
. . .
, ...
. .
- ,, , ,,, , ,. . ,,,, ~, ,
Example 2 . .
The nitroacetic acid chloride is prepared from 10.5 g of nitroacetic acid and 23 g of phosphorus pentachloride accord-ing to the proceduro described in Example 1. This acid chloride is added dropwise at 5-10, together with 200 ml of a 15 % soda solution, ~o a strongly stirred solution o~ 12.3 g ~0.05 mol) of 5-chloro-2-methylaminobenzophenone in 50 ml of chloro~orm.
At the end of the addition, the mixture is stirred for a ~urther 20 minutes at 5-10. The chloroform phase is separated, washed with water, dried over sodium sulphate and evaporated in vacuo at 30. The residue is crystallized from ether. After recrystallisation from methylene chloride/hexane, ~J
" . . .............. , "
. .. ... , ., . , . : .
. . . . .. .. .
~La35549~
there is obtained 2'-benzoyl-4'-chloro-N-methyl-2 nitro acetanilide of melting point 120-123 (decomp. and conversion into 6-chloro-1-methyl-3-nitro-4-phenylcarbostyril of mel~ing point 212-214).
1 ml of glacial acetic acid and 2 g of zinc dust are added to a solution of lg of 2'-benzoyl-4'-chloro-N-methyl-2-nitroacetanilide in 15 ml of me~hylene chloride. After the exothermal reaction, the mixture is stirred at room temperature for a further 15 minutes. After the addition of 5 ml of conc.
ammonia, the reaction mixture is partitioned between Nater and ether. The ether phase is extracted 3 x with 2-n hydrochloric acid. The ~xtracts are washed with ether and are made alkaline by addition of ammonia. The liberated bases are extracted with methylene chlorid0. The extracts are dried over sodium sulphate and evaporated to yield a crude product~ By chromatography on 15 g of silica gel with 10 % ethyl acetate in methylene chloride -and crystallisation from ether/hexane, there is obtained 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one of m.p.
130-13~.
- ;-, q~ ' .
. . .
, ...
. .
- ,, , ,,, , ,. . ,,,, ~, ,
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. In a process for the manufacture of benzodiasepine derivatives of the general formula I
wherein R signifies hydrogen or alkyl with up to 7 carbon atoms, R1 signifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, and 4-oxides thereof by cyclization a compound of the general formula IV
wherein R, R1 and R2 are as defined above and R3 signifies hydrogen or hydroxy the improvement which comprises preparing the compound of formula IV by reacting a benzophenone of the general formula II
wherein R, R1 and R2 are as defined above with a nitroacetic acid halide and reducing the obtained nitroacetyl compound of the general formula III
wherein R, R1 and R2 are as defined above, either a) with about 6 g. atom of zinc per mol. of compound III in order to obtain a compound of formula IV, wherein R3 is hydroxy, or b) with about 10 g. atom of zinc per mol. of compound III or catalytically in order to obtain a compound of formula IV, wherein R3 is hydrogen.
wherein R signifies hydrogen or alkyl with up to 7 carbon atoms, R1 signifies hydrogen, halogen or trifluoromethyl and R2 signifies phenyl, and 4-oxides thereof by cyclization a compound of the general formula IV
wherein R, R1 and R2 are as defined above and R3 signifies hydrogen or hydroxy the improvement which comprises preparing the compound of formula IV by reacting a benzophenone of the general formula II
wherein R, R1 and R2 are as defined above with a nitroacetic acid halide and reducing the obtained nitroacetyl compound of the general formula III
wherein R, R1 and R2 are as defined above, either a) with about 6 g. atom of zinc per mol. of compound III in order to obtain a compound of formula IV, wherein R3 is hydroxy, or b) with about 10 g. atom of zinc per mol. of compound III or catalytically in order to obtain a compound of formula IV, wherein R3 is hydrogen.
2. A process as claimed in claim 1, wherein nitroacetic acid chloride is used.
3. A process as claimed in claim 1, wherein the reduction is effected with zinc.
4. A process as claimed in claim 1, wherein R1 signifies halogen.
5. A process as claimed in claim 4, wherein R1 signifies chlorine.
6. A process as claimed in any one of claims 1 - 3, wherein R2 signifies phenyl.
7. A process as claimed in claim 1, wherein R signifies methyl.
8. A process as claimed in claim 7, wherein 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one is prepared.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH414974A CH596173A5 (en) | 1974-03-25 | 1974-03-25 | CNS Depressant 5-aryl-benzodiazepine prepn. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1055491A true CA1055491A (en) | 1979-05-29 |
Family
ID=4270728
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA222,888A Expired CA1055491A (en) | 1974-03-25 | 1975-03-24 | Process for the manufacture of benzodiazepine derivatives |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JPS50130777A (en) |
| AT (1) | AT351545B (en) |
| CA (1) | CA1055491A (en) |
| CH (1) | CH596173A5 (en) |
| DD (1) | DD118644A5 (en) |
| DK (1) | DK123675A (en) |
| ES (1) | ES435935A1 (en) |
| FI (1) | FI750380A (en) |
| NL (1) | NL7502283A (en) |
| NO (1) | NO751008L (en) |
| SE (1) | SE7503301L (en) |
| YU (1) | YU57775A (en) |
-
1974
- 1974-03-25 CH CH414974A patent/CH596173A5/en not_active IP Right Cessation
-
1975
- 1975-02-12 FI FI750380A patent/FI750380A/fi not_active Application Discontinuation
- 1975-02-26 NL NL7502283A patent/NL7502283A/en not_active Application Discontinuation
- 1975-03-10 YU YU00577/75A patent/YU57775A/en unknown
- 1975-03-20 JP JP50033118A patent/JPS50130777A/ja active Pending
- 1975-03-21 SE SE7503301A patent/SE7503301L/xx unknown
- 1975-03-24 ES ES435935A patent/ES435935A1/en not_active Expired
- 1975-03-24 NO NO751008A patent/NO751008L/no unknown
- 1975-03-24 DD DD184989A patent/DD118644A5/xx unknown
- 1975-03-24 CA CA222,888A patent/CA1055491A/en not_active Expired
- 1975-03-24 AT AT224775A patent/AT351545B/en not_active IP Right Cessation
- 1975-03-24 DK DK123675A patent/DK123675A/da not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AT351545B (en) | 1979-07-25 |
| JPS50130777A (en) | 1975-10-16 |
| SE7503301L (en) | 1975-09-26 |
| NO751008L (en) | 1975-09-26 |
| DD118644A5 (en) | 1976-03-12 |
| CH596173A5 (en) | 1978-02-28 |
| NL7502283A (en) | 1975-09-29 |
| FI750380A (en) | 1975-09-26 |
| YU57775A (en) | 1982-05-31 |
| ES435935A1 (en) | 1976-12-16 |
| DK123675A (en) | 1975-09-26 |
| ATA224775A (en) | 1979-01-15 |
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