CA1178289A - Process for the preparation of n-¬2-¬¬¬5- (dimethylamino)-methyl-2- furanyl|methyl|thio|ethyl|-n'-methyl-2-nitro- 1,1-ethenediamine - Google Patents
Process for the preparation of n-¬2-¬¬¬5- (dimethylamino)-methyl-2- furanyl|methyl|thio|ethyl|-n'-methyl-2-nitro- 1,1-ethenediamineInfo
- Publication number
- CA1178289A CA1178289A CA000429775A CA429775A CA1178289A CA 1178289 A CA1178289 A CA 1178289A CA 000429775 A CA000429775 A CA 000429775A CA 429775 A CA429775 A CA 429775A CA 1178289 A CA1178289 A CA 1178289A
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- Prior art keywords
- methyl
- nitro
- formula
- thio
- dimethylamino
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
ABSTRACT
A new process for the preparation of N-[2-[[[5-(dimethyl-amino)-methyl-2-furanyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine (ranitidine) of the formula an its phsiologically acceptable acid addition salts is described, wherein 2-[[[5-(dimethylamino)methyl-2-furanyl]-methyl]thio]ethane-amine of the formula is reacted with 1-nitro-3-methyl-keteneimine of the formula CH3N=C=CHNO2 to give the desired compound. 1-nitro-3-methyl-keteneimine is formed in situ by reacting 1-methylthio-1-methylamino-2-nitroethane of the formula in a polar organic solvent, such as methanol or acetonitrile, with a salt of a heavy metal, such as AgNO3, CuCl, dissolved in the same solvent, in the presence of a proton acceptor, such as tri-ethylamine, at room temperature.
Ranitidine is a valuable medicine in the treatment of ulcer diseases. Owing to a very simple course of the reaction and an extrodinary short reaction time, the process is excellently suitable for the industrial scale production.
A new process for the preparation of N-[2-[[[5-(dimethyl-amino)-methyl-2-furanyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine (ranitidine) of the formula an its phsiologically acceptable acid addition salts is described, wherein 2-[[[5-(dimethylamino)methyl-2-furanyl]-methyl]thio]ethane-amine of the formula is reacted with 1-nitro-3-methyl-keteneimine of the formula CH3N=C=CHNO2 to give the desired compound. 1-nitro-3-methyl-keteneimine is formed in situ by reacting 1-methylthio-1-methylamino-2-nitroethane of the formula in a polar organic solvent, such as methanol or acetonitrile, with a salt of a heavy metal, such as AgNO3, CuCl, dissolved in the same solvent, in the presence of a proton acceptor, such as tri-ethylamine, at room temperature.
Ranitidine is a valuable medicine in the treatment of ulcer diseases. Owing to a very simple course of the reaction and an extrodinary short reaction time, the process is excellently suitable for the industrial scale production.
Description
~7~
A PROCESS FOR THE PREPARATION OF N-[2-[Lr5-~DIM~THYL~MINO)~METHYL-
A PROCESS FOR THE PREPARATION OF N-[2-[Lr5-~DIM~THYL~MINO)~METHYL-
2-FURANY~ METHYL~ THIO]ETHYL]-N'~METHYL-2--NITRO~1, 1-ETHENEDIAMINE
The present invention relates to a new process for the preparation of N-~2-[[[5-(dimethylamino)-methyl~2~furanyl~ -methyl]
thio~ ethyl]-N'-methyl~2-nitro~ ethenediamine of the formula
The present invention relates to a new process for the preparation of N-~2-[[[5-(dimethylamino)-methyl~2~furanyl~ -methyl]
thio~ ethyl]-N'-methyl~2-nitro~ ethenediamine of the formula
3)2NCH2 ~ / ~ ,, CH2scH2cH2NHcNHcH3 and physiologically acceptable acicl addition salts thereof, such as hydrochloride, hydrobromide. The compouncl is known under the generic name ranitidine~ Ranitidine was first described in the German Publication 27 34 070 as a selective H2-antagonist, i.e. a compound which inhibits the secretion of gastric acidr which is stimulated by the histamine-H2-receptors. Ranitidine represents, preferably in the form of its hydrochloride, a valuable medicine for the treatment of ulcer diseases.
The above stated German Publication also describes several methods for the synthesis of ranitidine. In the most advantageous synthesis as starting compound there was used 5-(N,N-dimethylamino)-methyl-2-hydroxy-methylfuran of the formula (CH3)2NCH2 \ ~ ~ / CH2 1~1 a known compound which can be obtained in good yield (70%)from 2-furan-methanol (furfuryl alcohol) by means of Mannich's reaction in the manner described by Gill and Ing., J. Chem. Soc. 4728-4731 (195~).
~; 1 ~ .~
5-(N,N-dimethylamino~methyl-2-hydroxy-methylfuran was then reacted with cysteamine hydrochloride to 2-L[[5~dimethylamino)-methyl-2-furany~ methyl~ thio] ethaneamine (Example A of the stated German Publication, yield 54%) of the formula ( 3)2 2 ~ \ ,-CH2SCH2CH2NH2 which is a valuable intermediate in the synthesis of ranitidine.
1~ This intermediate can then`~e reacted with l-methyl-thio-l-methyl-amino-2-nitroet~lene of t~le formula CH3S-C-N~IC~I
to give ranitidine (Example 15 of the mentioned German publication?~
On the other hand the intermecliate compo~d can also be first reacted with l,l-bis(methyl~hio)-2-nitroethene of the formula ~CH3S)2C=C~INO2 to give N-[2-[l[5-(dimethylamino)methyl-2-furanyl~ methyl~ thi~ ethy~
-N'-methyl-thiourea, which is then reacted with methylamine to the desired compound.
The disadvantages of the prior art processes are the necessity to use an expensive chemical (cysteamine hydrochloride) in the step of the preparation of the intermediate compound as well as poor yields in this step. In the last step of the reaction of the intermediate compound to give ranitidine, the toxic, malodorous and polluting methyl mercaptan is formed. Additionally, the re-action takes up quite a long period of time~
A more recent German Publication 31 00 364 describes the substitution or less expensive 2-chloroethylamine hydrochloride or ethyleneimine for the expensive cysteamine as the key compound in the synthesis of ranitidine. In this reaction, however, the ~ ~ 7~
starting compound 5~(N,N-dimethylamino~methyl-2-hyd.roxymethylfuran must first be reacted to the corresponding thiol, which is one o~
the key intermediates, thus rendering the synthesis longer hy two additional steps.
The key reaction, i.e. the reactioll between the two inter-mediate compounds 5-(N,M-dimethylamino)methyl-2-thiomethylfuran in the form of its salt with oxalic acid and l-(2~chloroethyl)amino-l-methylamino-2-nitroethene is extremely long.
The o~ject of the present invention is to provide a process for the preparation of ranitidine in good yields w.ithin very short times, thereby saving energy, using, instead of the expensive cysteamine hydrochloride, the low-priced and readily available 2-mercapto-e~hanol, which is even less expensive than 2-chloro~ethylamine hydrochloride, carrying out the key reaction at room temperature and avoiding the formation of the toxic methyl mercaptan.
This object can be achievecl by the process of the invention, wherein 2- [~[5-(dimethylamino)methyl-2-furany~ methyl] thio]-ethane-amine, prepared according to the process which is described in our co-pending Canadian Patent ~pplication 429,776 (corresponding to Yugoslavian application P 2607/82 of November 22, 1982), is reacted with the extremely reactive l-nitro 3-methyl-keteneimine (N-methyl-nitroketeneimine) o~ khe formula CH N=C-CHNO
which is a new compound and has not yet been described in literature, to give ranitidine.
~ method for eliminating methyl mercaptan from N-substi-tuted N'-cyano-S-me!thyl-isothioureas to yiPld guanidine derivatives is known from literature [A.F. Ferris and B.A. Schultz, J. Org. Chem.
26 (1963), 71-74; C.G. McCarty et al, J. Org. Chem. 35 (1970), 2067-2069~ . The reaction proceeds via extremely reactive inter-mediate compounds, N-cyanocarbodiimides, which are formed in situ.
:. `
Said compounds, however, are not stable, hence they cannot be isolated and they are difficult to characterize.
A similar reaction of elimination of methyl mercaptan from l-methylthio-l-methylamino~2-nitroethene of the formula CHNO
" 2 whereat there is formed-in- situ the intermediate, extremely reactive ~ . _.
new l-nitro-3-methyl-keteneimine (N-methylnitroketeneimine) of the formula CH3M=C=C~N02 has not yet been described in literature neither i5 known such a method for the synthesis of keteneimiIles. Such a course of react.~on~ however, was surprisin~ly found in the process of the invention.
The key step of the new inventive procese for the synthesis of ranitidine is the reaction between 2-[[[5-(dimethylamino)methyl-2-furany~ methyl]thio~ethaneamine and 1-nitro-3-methyl-keteneimine formed _ situ. The latter compound is formed in that to a solu-tion of a salt of a heavy metal, such as AgN03, CuC12, Cucl, HgC12, ZnC12 etc., as a catalyst in an organic solvent, such a methanol or acetonitrile, there is added a solution of l-methylthio~l-methyl-2a amino-2-nitroethene and triethylamine in the same solvent at room temperature, Triethylamine is used as a proton acceptor. The metal mercaptide, which quantita~ively separates at once, is filtered off.
In this way there is avoided the polution by the toxic methyl mercaptan.
The reaction proceeds extremely rapidly, within a few minutes, at room temperature to give ranitidine. For a good yield of the synthesis and for a swift course of the reaction the succes-sion of the addition of the reactants as shown in the Examples is of import~nce.
3 ~ 7~
1-nitro-3-methyl~keteneimine, formed 'n SitU, can be detected by the IR spectrum oE the reaction mixture which shows an absorption at 217Q cm l~ which is characteristic ~or the ketene-imine ~C=C=N-l a~sorption range (2200-2050 cm l~, The formation of 1-nitro-3~methyl-ket2neimine can indirec-tly be detected by means of a separate reactiorl with a lower alcohol, such as methanol. Thereby ~he new crystalline l-methoxy-l-methylamino-2-nitroethene is formed;
CH3N=C=CHNO2 _~ 3 \ C-CHNO
It is known that keteneimines can be rapidly reacted with alcohols to give well crystallized products.
The invention is illustrated by the following non-limitative Examples, ~xample l ~ . _ .
N-C2- LC r5-~dimeth lamino)meth l-2-furanxl me~l3 thio3 ethyl~-N'-meth~l~2-ni-tro-l,l'~ethened'iamine (ranitldine) CuCl (198 mg, 2 mmole) is dissolved in acetonitrile (25 ml~.
To this solution a solution of 2-LL[5-(dimethylamino)methyl-2-furany~ methyl] thio~ ethaneamine (428 mg, 2 mmole), l-methyl-thio-l-methylamino-2~nitroethene (296 mg7 2 mmole) and triethylamine (200 mg) in acetonitrile (10 ml) is added dropwise within 5 minutes under stirring. The formed precipitate is filtered off by suction, the filtrate is evaporated to half of its original volume. Chloroform (30 ml) i5 added thereto and it is extracted with aqueous ammonia (3 x 20 ml). The ammoniacal extracts are discarded. The organic phase is dried (Na2SO~) r filtered and evaporated.
Thus pure ranitidine is obtained, which, with respect to its melting point, IR, NMR and MS, is identical to the product obtained in Example 15 of the German Publication 27 34 070.
Example 2 .
N-C2-[[c5-(dlmeth lamino)m'eth 1-2-furan 1~ methyl____ o~ethy~ -N'--methyl-2-nitro-1,'1-ethene'dia~ine (ranitidine) AgNO3 (340 ~, 2 mmo]e) is clissolved in methanol (12 ml).
To this solution a solution of 2-[~r5-~dimethylamino)methyl-2-furanyl]-methyl]thio~2thaneamine (214 mg, 1 mmole), l-methylthio-1-methyl-amino-2-nitroethene (163 ms, 1.1 mmole) and triethylamine (100 mg) is added dropwise under slow stirring within 5 minutesO
The formed precipitate is filtered off r chloroform (20 ml) is added to the filtrate and it is extracted with HCl (1:1, 15 ml). The aqueous phase is neutralized with NaHCO3 and extracted twice with chloroform (30 ml each time). The combined extracts are dried (Na2-SO~) and evapo.rated. Pure ranitidine is obtainecl. W:Lth respect to its melting point, IR, NMR and MS, the product is identical to the product obtained in Example 15 oP the ~erman Publicati.on 27 34 070.
Exampl _3 Detection of l-nitro~3-meth l-keteneimine in the reaction mixture Formation of l-me~hoxy-l-methylamino-2-nitroethene ~gNO3 (170 mg, 1 mmole) is dissolved in methanol (6 ml).
To this solution 1-methylthio-1-methylamino-2-nitroethene (30 m~, 0.2 mmole) is added, followed by triethylamine (100 mg). Silver mercaptide separates at once. The precipitate is filtered, the filtr~te is evaporated and the product is crystallized by the addi-tion of i-propanol (2 ml). Thus l-methoxy-l-methylamino~2-nitro-ethene, m.p. 98-103C, is formecl in ~ood yield (90%). Melting point after recrystallization from abs. ethanol: 112-114C.
Analysis for C4H8N2O3 Calc.: C 35.36 % H 6.10 % N 21.20 ~
Foundo C 36.13 % H 6.24 % N 21.30 %
M = 132 NMR(CDC13): 7.0 and 7.1 (two s, NHMe; 6.16 (s, OMe); 3.36 (s, CH), 1.4 (broad, NH-).
The above stated German Publication also describes several methods for the synthesis of ranitidine. In the most advantageous synthesis as starting compound there was used 5-(N,N-dimethylamino)-methyl-2-hydroxy-methylfuran of the formula (CH3)2NCH2 \ ~ ~ / CH2 1~1 a known compound which can be obtained in good yield (70%)from 2-furan-methanol (furfuryl alcohol) by means of Mannich's reaction in the manner described by Gill and Ing., J. Chem. Soc. 4728-4731 (195~).
~; 1 ~ .~
5-(N,N-dimethylamino~methyl-2-hydroxy-methylfuran was then reacted with cysteamine hydrochloride to 2-L[[5~dimethylamino)-methyl-2-furany~ methyl~ thio] ethaneamine (Example A of the stated German Publication, yield 54%) of the formula ( 3)2 2 ~ \ ,-CH2SCH2CH2NH2 which is a valuable intermediate in the synthesis of ranitidine.
1~ This intermediate can then`~e reacted with l-methyl-thio-l-methyl-amino-2-nitroet~lene of t~le formula CH3S-C-N~IC~I
to give ranitidine (Example 15 of the mentioned German publication?~
On the other hand the intermecliate compo~d can also be first reacted with l,l-bis(methyl~hio)-2-nitroethene of the formula ~CH3S)2C=C~INO2 to give N-[2-[l[5-(dimethylamino)methyl-2-furanyl~ methyl~ thi~ ethy~
-N'-methyl-thiourea, which is then reacted with methylamine to the desired compound.
The disadvantages of the prior art processes are the necessity to use an expensive chemical (cysteamine hydrochloride) in the step of the preparation of the intermediate compound as well as poor yields in this step. In the last step of the reaction of the intermediate compound to give ranitidine, the toxic, malodorous and polluting methyl mercaptan is formed. Additionally, the re-action takes up quite a long period of time~
A more recent German Publication 31 00 364 describes the substitution or less expensive 2-chloroethylamine hydrochloride or ethyleneimine for the expensive cysteamine as the key compound in the synthesis of ranitidine. In this reaction, however, the ~ ~ 7~
starting compound 5~(N,N-dimethylamino~methyl-2-hyd.roxymethylfuran must first be reacted to the corresponding thiol, which is one o~
the key intermediates, thus rendering the synthesis longer hy two additional steps.
The key reaction, i.e. the reactioll between the two inter-mediate compounds 5-(N,M-dimethylamino)methyl-2-thiomethylfuran in the form of its salt with oxalic acid and l-(2~chloroethyl)amino-l-methylamino-2-nitroethene is extremely long.
The o~ject of the present invention is to provide a process for the preparation of ranitidine in good yields w.ithin very short times, thereby saving energy, using, instead of the expensive cysteamine hydrochloride, the low-priced and readily available 2-mercapto-e~hanol, which is even less expensive than 2-chloro~ethylamine hydrochloride, carrying out the key reaction at room temperature and avoiding the formation of the toxic methyl mercaptan.
This object can be achievecl by the process of the invention, wherein 2- [~[5-(dimethylamino)methyl-2-furany~ methyl] thio]-ethane-amine, prepared according to the process which is described in our co-pending Canadian Patent ~pplication 429,776 (corresponding to Yugoslavian application P 2607/82 of November 22, 1982), is reacted with the extremely reactive l-nitro 3-methyl-keteneimine (N-methyl-nitroketeneimine) o~ khe formula CH N=C-CHNO
which is a new compound and has not yet been described in literature, to give ranitidine.
~ method for eliminating methyl mercaptan from N-substi-tuted N'-cyano-S-me!thyl-isothioureas to yiPld guanidine derivatives is known from literature [A.F. Ferris and B.A. Schultz, J. Org. Chem.
26 (1963), 71-74; C.G. McCarty et al, J. Org. Chem. 35 (1970), 2067-2069~ . The reaction proceeds via extremely reactive inter-mediate compounds, N-cyanocarbodiimides, which are formed in situ.
:. `
Said compounds, however, are not stable, hence they cannot be isolated and they are difficult to characterize.
A similar reaction of elimination of methyl mercaptan from l-methylthio-l-methylamino~2-nitroethene of the formula CHNO
" 2 whereat there is formed-in- situ the intermediate, extremely reactive ~ . _.
new l-nitro-3-methyl-keteneimine (N-methylnitroketeneimine) of the formula CH3M=C=C~N02 has not yet been described in literature neither i5 known such a method for the synthesis of keteneimiIles. Such a course of react.~on~ however, was surprisin~ly found in the process of the invention.
The key step of the new inventive procese for the synthesis of ranitidine is the reaction between 2-[[[5-(dimethylamino)methyl-2-furany~ methyl]thio~ethaneamine and 1-nitro-3-methyl-keteneimine formed _ situ. The latter compound is formed in that to a solu-tion of a salt of a heavy metal, such as AgN03, CuC12, Cucl, HgC12, ZnC12 etc., as a catalyst in an organic solvent, such a methanol or acetonitrile, there is added a solution of l-methylthio~l-methyl-2a amino-2-nitroethene and triethylamine in the same solvent at room temperature, Triethylamine is used as a proton acceptor. The metal mercaptide, which quantita~ively separates at once, is filtered off.
In this way there is avoided the polution by the toxic methyl mercaptan.
The reaction proceeds extremely rapidly, within a few minutes, at room temperature to give ranitidine. For a good yield of the synthesis and for a swift course of the reaction the succes-sion of the addition of the reactants as shown in the Examples is of import~nce.
3 ~ 7~
1-nitro-3-methyl~keteneimine, formed 'n SitU, can be detected by the IR spectrum oE the reaction mixture which shows an absorption at 217Q cm l~ which is characteristic ~or the ketene-imine ~C=C=N-l a~sorption range (2200-2050 cm l~, The formation of 1-nitro-3~methyl-ket2neimine can indirec-tly be detected by means of a separate reactiorl with a lower alcohol, such as methanol. Thereby ~he new crystalline l-methoxy-l-methylamino-2-nitroethene is formed;
CH3N=C=CHNO2 _~ 3 \ C-CHNO
It is known that keteneimines can be rapidly reacted with alcohols to give well crystallized products.
The invention is illustrated by the following non-limitative Examples, ~xample l ~ . _ .
N-C2- LC r5-~dimeth lamino)meth l-2-furanxl me~l3 thio3 ethyl~-N'-meth~l~2-ni-tro-l,l'~ethened'iamine (ranitldine) CuCl (198 mg, 2 mmole) is dissolved in acetonitrile (25 ml~.
To this solution a solution of 2-LL[5-(dimethylamino)methyl-2-furany~ methyl] thio~ ethaneamine (428 mg, 2 mmole), l-methyl-thio-l-methylamino-2~nitroethene (296 mg7 2 mmole) and triethylamine (200 mg) in acetonitrile (10 ml) is added dropwise within 5 minutes under stirring. The formed precipitate is filtered off by suction, the filtrate is evaporated to half of its original volume. Chloroform (30 ml) i5 added thereto and it is extracted with aqueous ammonia (3 x 20 ml). The ammoniacal extracts are discarded. The organic phase is dried (Na2SO~) r filtered and evaporated.
Thus pure ranitidine is obtained, which, with respect to its melting point, IR, NMR and MS, is identical to the product obtained in Example 15 of the German Publication 27 34 070.
Example 2 .
N-C2-[[c5-(dlmeth lamino)m'eth 1-2-furan 1~ methyl____ o~ethy~ -N'--methyl-2-nitro-1,'1-ethene'dia~ine (ranitidine) AgNO3 (340 ~, 2 mmo]e) is clissolved in methanol (12 ml).
To this solution a solution of 2-[~r5-~dimethylamino)methyl-2-furanyl]-methyl]thio~2thaneamine (214 mg, 1 mmole), l-methylthio-1-methyl-amino-2-nitroethene (163 ms, 1.1 mmole) and triethylamine (100 mg) is added dropwise under slow stirring within 5 minutesO
The formed precipitate is filtered off r chloroform (20 ml) is added to the filtrate and it is extracted with HCl (1:1, 15 ml). The aqueous phase is neutralized with NaHCO3 and extracted twice with chloroform (30 ml each time). The combined extracts are dried (Na2-SO~) and evapo.rated. Pure ranitidine is obtainecl. W:Lth respect to its melting point, IR, NMR and MS, the product is identical to the product obtained in Example 15 oP the ~erman Publicati.on 27 34 070.
Exampl _3 Detection of l-nitro~3-meth l-keteneimine in the reaction mixture Formation of l-me~hoxy-l-methylamino-2-nitroethene ~gNO3 (170 mg, 1 mmole) is dissolved in methanol (6 ml).
To this solution 1-methylthio-1-methylamino-2-nitroethene (30 m~, 0.2 mmole) is added, followed by triethylamine (100 mg). Silver mercaptide separates at once. The precipitate is filtered, the filtr~te is evaporated and the product is crystallized by the addi-tion of i-propanol (2 ml). Thus l-methoxy-l-methylamino~2-nitro-ethene, m.p. 98-103C, is formecl in ~ood yield (90%). Melting point after recrystallization from abs. ethanol: 112-114C.
Analysis for C4H8N2O3 Calc.: C 35.36 % H 6.10 % N 21.20 ~
Foundo C 36.13 % H 6.24 % N 21.30 %
M = 132 NMR(CDC13): 7.0 and 7.1 (two s, NHMe; 6.16 (s, OMe); 3.36 (s, CH), 1.4 (broad, NH-).
Claims (5)
IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the preparation of N-[2-[[[5-(dimethylamino)-methyl-2-furfanyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine of the formula and its physiologically acceptable acid addition salts, wherein 2-[[[5-(dimethylamino)methyl-2-furanyl]methyl]thio]ethaneamine of the formula is reacted with 1-nitro-3-methyl keteneimine of the formula CH3N=C=CHNO2 at room temperature.
2. A process according to claim 1, wherein 1-nitro-3-methyl-keteneimine is formed in situ by reacting 1-methyl-thio-1-methylamino-2-nitroethene of the formula dissolved in a polar organic solvent, with a salt of a heavy metal, dissolved in the same solvent, in the presence of a proton acceptor at room temperature.
3. A process according to claim 2, wherein methanol or acetonitrile is used as the polar organic solvent.
4. A process according to claim 2, wherein AgNO3, CuCl2, CuCl, HgCl2 or ZnCl2 is used as the salt of a heavy metal.
5. A process according to claim 2, wherein triethylamine is used as the proton acceptor.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU2608/82A YU42819B (en) | 1982-11-22 | 1982-11-22 | Process for preparing n-/2-///5-(dimethyl-amino)-methyl-2-furanyl/methyl/thio/ethyl-n'-methyl-2-nitro-1,1-ethene diamine |
| YUP2608/82 | 1982-11-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1178289A true CA1178289A (en) | 1984-11-20 |
Family
ID=25558386
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000429775A Expired CA1178289A (en) | 1982-11-22 | 1983-06-06 | Process for the preparation of n-¬2-¬¬¬5- (dimethylamino)-methyl-2- furanyl|methyl|thio|ethyl|-n'-methyl-2-nitro- 1,1-ethenediamine |
Country Status (12)
| Country | Link |
|---|---|
| KR (1) | KR870000165B1 (en) |
| AT (1) | AT386200B (en) |
| CA (1) | CA1178289A (en) |
| CS (1) | CS237339B2 (en) |
| DD (1) | DD209830A5 (en) |
| ES (1) | ES8500925A1 (en) |
| FI (1) | FI832246L (en) |
| HU (1) | HU194849B (en) |
| PL (1) | PL242065A1 (en) |
| PT (1) | PT76760B (en) |
| SU (1) | SU1194277A3 (en) |
| YU (1) | YU42819B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU207308B (en) * | 1990-11-09 | 1993-03-29 | Richter Gedeon Vegyeszet | Process for producing 1- /2-/5-/dimethyl-amino-methyl/-2-/furyl-methyl-thio/-ethyl//- -amino-1-/methyl-amino-2-nitro-ethylene |
| HU210849B (en) * | 1990-11-09 | 1995-08-28 | Richter Gedeon Vegyeszet | Process for preparing furil derivatives |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1565966A (en) * | 1976-08-04 | 1980-04-23 | Allen & Hanburys Ltd | Aminoalkyl furan derivatives |
| PT72320B (en) * | 1980-01-08 | 1982-07-23 | Glaxo Group Ltd | Process for preparation of a furan derivative |
| ES501844A0 (en) * | 1981-05-02 | 1982-11-01 | Especialidades Farmaco Terape | PROCEDURE FOR THE OBTAINING OF A COMPOUND DERIVED FROM ALCOHOL FURFURILICO |
-
1982
- 1982-11-22 YU YU2608/82A patent/YU42819B/en unknown
-
1983
- 1983-05-16 AT AT0177783A patent/AT386200B/en not_active IP Right Cessation
- 1983-05-19 PL PL24206583A patent/PL242065A1/en unknown
- 1983-05-24 HU HU831827A patent/HU194849B/en not_active IP Right Cessation
- 1983-05-25 PT PT76760A patent/PT76760B/en unknown
- 1983-05-26 CS CS833801A patent/CS237339B2/en unknown
- 1983-05-26 DD DD83251290A patent/DD209830A5/en not_active IP Right Cessation
- 1983-05-31 SU SU833598339A patent/SU1194277A3/en active
- 1983-06-06 CA CA000429775A patent/CA1178289A/en not_active Expired
- 1983-06-14 ES ES523235A patent/ES8500925A1/en not_active Expired
- 1983-06-20 FI FI832246A patent/FI832246L/en not_active Application Discontinuation
- 1983-06-20 KR KR1019830002760A patent/KR870000165B1/en active Pre-grant Review Request
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| Publication number | Publication date |
|---|---|
| YU42819B (en) | 1988-12-31 |
| DD209830A5 (en) | 1984-05-23 |
| PT76760B (en) | 1986-01-14 |
| KR870000165B1 (en) | 1987-02-13 |
| PL242065A1 (en) | 1984-07-30 |
| SU1194277A3 (en) | 1985-11-23 |
| KR840007089A (en) | 1984-12-05 |
| PT76760A (en) | 1983-06-01 |
| AT386200B (en) | 1988-07-11 |
| CS237339B2 (en) | 1985-07-16 |
| YU260882A (en) | 1984-10-31 |
| ATA177783A (en) | 1987-12-15 |
| ES523235A0 (en) | 1984-11-16 |
| CS380183A2 (en) | 1984-12-14 |
| FI832246L (en) | 1984-05-23 |
| FI832246A0 (en) | 1983-06-20 |
| ES8500925A1 (en) | 1984-11-16 |
| HU194849B (en) | 1988-03-28 |
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