GB2033382A - Production of N-(4'-Chloro-3- sulphamoyl-benzenesulphonyl)-N- methyl-2-aminomethyl-2-methyl tetrahydrofuran - Google Patents
Production of N-(4'-Chloro-3- sulphamoyl-benzenesulphonyl)-N- methyl-2-aminomethyl-2-methyl tetrahydrofuran Download PDFInfo
- Publication number
- GB2033382A GB2033382A GB7933926A GB7933926A GB2033382A GB 2033382 A GB2033382 A GB 2033382A GB 7933926 A GB7933926 A GB 7933926A GB 7933926 A GB7933926 A GB 7933926A GB 2033382 A GB2033382 A GB 2033382A
- Authority
- GB
- United Kingdom
- Prior art keywords
- methyl
- mefrusid
- chloro
- solution
- aminomethyl
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 10
- SMNOERSLNYGGOU-UHFFFAOYSA-N Mefruside Chemical compound C=1C=C(Cl)C(S(N)(=O)=O)=CC=1S(=O)(=O)N(C)CC1(C)CCCO1 SMNOERSLNYGGOU-UHFFFAOYSA-N 0.000 title claims description 28
- 238000000034 method Methods 0.000 claims abstract description 27
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 239000007864 aqueous solution Substances 0.000 claims abstract description 7
- CADAUKUITLKLMI-UHFFFAOYSA-N 4-chloro-3-sulfamoylbenzenesulfonyl chloride Chemical compound NS(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1Cl CADAUKUITLKLMI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 4
- 239000003513 alkali Substances 0.000 claims abstract description 4
- CWVGGBWOKGYTHZ-UHFFFAOYSA-N azanium;methyl-[(2-methyloxolan-2-yl)methyl]azanium;sulfate Chemical compound [NH4+].[O-]S([O-])(=O)=O.C[NH2+]CC1(C)CCCO1 CWVGGBWOKGYTHZ-UHFFFAOYSA-N 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 229960004678 mefruside Drugs 0.000 claims description 26
- 239000000243 solution Substances 0.000 claims description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003610 charcoal Substances 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 8
- -1 N-(4'-chloro-3'sulphamoylbenzenesulphonyl)-N-methyl-2amino-methyl-2-methyl-tetrahydrofurane Chemical compound 0.000 claims description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000002198 insoluble material Substances 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000011403 purification operation Methods 0.000 claims description 2
- 239000011877 solvent mixture Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
Classifications
-
- 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
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
Abstract
The process for production of the above compound comprises reacting 4-chloro-3-sulphamoyl-benzene- sulphonic acid chloride in a chlorinated hydrocarbon solvent, with an aqueous solution (containing alkali group carbonate) of N-methyl-2- aminomethyl-2-methyl- tetrahydrofurane-ammonium hydrogen sulphate at a temperature between 20 and 100 DEG C.
Description
SPECIFICATION
Production of N-(4'-chloro-3'sulphamoylbenzenesulphonyl)-N-methyl-2amino-methyl-2-methyl-tetrahydrofurane
The present invention relates to an unobvious process for the production of the known compound N-(4'-chloro-3'-sulphamoyl benzenesuiphonyl )-N-methyl-2-aminomethyl-2- methyl-tetrahydrofurane and the pharmaceutical use thereof.
The above-mentioned compound is known as a diuretic agent under the generic name "Mefrusid". Hitherto, it was prepared by reacting 4-chloro-3-sulphamoyl-benzene-suíphonic acid chloride (called Sulphochloride 1 500 in the following text) with N-methyl-2-aminomethyl-2methyl-tetra-hydrofu rane-a mmonium hydrogen sulphate (called Amine Sulphate 1 500 in the following text), the reaction being carried out in a solvent mixture of methyl ethyl ketone/water or acetone/water.
In order to obtain from the resulting crude
Mefrusid a pure active compound which is suitable for pharmaceutical requirements, additional purification steps were hitherto necessary. The crude product was hitherto dissolved in sodium hydroxide solution and, after treatment with active charcoal, the solution was filtered and the product was precipitated from the filtrate with ammonium chloride solution and then isolated. This purification step was followed by a further recrystallisation by dissolving the product in hot, aqueous methanol, treatment of the solution with active charcoal, filtration, renewed crystallisation and subsequent isolation of the purified active compound.
These purification operations are timeconsuming and expensive, pollute the effluent and greatly reduce the yield.
According to the present invention we provide a process for the production of a compound which is N-(4'-chloro-3'-sulphamoylbenzenesu Iphonyl)-N-methyl-2-aminomethyl-2methyl-tetrahydrofurane, in which 4-chloro-3sulphamoyl-benzene-sulphonic acid chloride is reacted, in a chlorinated hydrocarbon, with an aqueous solution, containing potassium carbonate, of N-methyl-2-aminomethyl-2-methyl- tetrahydrofurane-ammonium hydrogen sulphate at a temperature between 20 and 1000C.
A particularly preferred process for producing
Mefrusid in a pure form is one in which
Sulphochloride 1 500 is dissolved in a liquid chlorinated hydrocarbon, under the influence of heat, the insoluble material is filtered off and the filtrate is reacted with an aqueous potassium carbonate-Amine-Suiphate 1 500 solution at temperatures between 40 and 800 C, the chlorinated hydrocarbon is then distilled off, the precipitated Mefrusid is dissolved by heating, with the addition of a C1 to C4 alkanol, and, after filtering the mixture and cooling the solution, the
Mefrusid which has crystallised out is then isolated.
The Mefrusid obtained in this manner is already so pure that, after simple, single recrystallisation in aqueous alcohol, it can be employed for the preparation of medicaments.
Chlorinated hydrocarbons which are particularly advantageous to use are chlorobenzene or, preferably, 1 ,2-dichloroethane.
Alkanols with 1 to 4 carbon atoms, in particular ethanol, or preferably methanol, are preferably used for the recrystallisation.
The reaction according to the invention is appropriately preferably carried out in a temperature range from 40 to 800C, and especially from 50 to 700C.
It is exceptionally surprising that the reaction of
Sulphochloride 1 500 with potassium carbonate
Amine Sulphate 1 500 can be carried out using chlorinated hydrocarbons as solvents and that such a pure Mefrusid is obtained by this procedure.
The process according to the invention has a number of advantages. Compared with the process known hitherto, changing of solvents, using active charcoal and the addition of ammonium chloride to precipitate the Mefrusid are dispensed with. Furthermore, the yield of pure
Mefrusid is higher than in the case of the process known hitherto.
The following Example illustrates the process of the present invention.
Example
100 g of Sulphochloride 1 500 are dissolved in 1 880 g of 1 2-dichloroethane at the boil.
Insoluble material is filtered off from the hot solution. The filtrate is run into an aqueous solution of 160 ml of water, 70 g of potassium carbonate and 70 g of Amine Sulphate 1 500. The mixture is stirred at 50--600C for 5 hours. 300 ml of water are then added and the aqueous layer is separated off. The 1,2-dichloroethane is distilled off with steam. The 1 2-dichloroethane which has distilled off is dried with calcium chloride, after separating off the water, and is available for re-use.
The same amount by volume of methanol is added to the aqueous Mefrusid suspension, 5
10 g of active charcoal are added and the mixture is heated to the boil.
The hot solution is filtered. The Mefrusid is crystallised out from the cooled filtrate. It is filtered off and washed with 3 x 100 ml of water.
The moist Mefrusid is recrystallised once from aqueous methanol and a Mefrusid which corresponds to the purity requirements for medicaments is obtained.
Claims
1. A process for the production of a compound which is N-(4'-chloro-3'-sulphamoyl benzenesu Iphonyl)-N-methyl-2-aminomethyl-2- methyl-tetrahydrofurane, in which 4-chloro-3sulphamoyl-benzene-sulphonic acid chloride is reacted, in a chlorinated hydrocarbon, with an aqueous solution, containing alkali carbonate, of
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (9)
1. A process for the production of a compound which is N-(4'-chloro-3'-sulphamoyl benzenesu Iphonyl)-N-methyl-2-aminomethyl-2- methyl-tetrahydrofurane, in which 4-chloro-3sulphamoyl-benzene-sulphonic acid chloride is reacted, in a chlorinated hydrocarbon, with an aqueous solution, containing alkali carbonate, of
N-methyl-2-aminomethyl-2-methyltetrahydrofurane-ammonium hydrogen sulphate at a temperature between 20 and 1 000C.
2. A process according to Claim 1, in which the alkali carbonate is potassium carbonate.
3. A process according to Claim 1, in which the chlorinated hydrocarbon is 1,2-dichloroethane.
4. A process according to Claim 1 or 2, in which the reaction is carried out at a temperature of50to700C.
5. A process according to any of Claims 1 to 3, in which the compound obtained is recrystallised from an aqueous alcohol solution.
6. A process according to Claim 4, in which the alcohol is an alkanol with 1 to 4 carbon atoms.
7. A process according to Claim 5, in which the alkanol is methanol,.
8. A process according to Claim 1, when carried out substantially as described in the
Example.
9. N-(4'-chloro-3'-sulphamoylbenzenesulphonyl)-N-methyl-2-aminomethyl-2 methyl-tetrahydrofurane when produced by the process of any of the foregoing claims.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782843040 DE2843040A1 (en) | 1978-10-03 | 1978-10-03 | METHOD FOR PRODUCING N- (4'-CHLORINE-3'-SULFAMOYL-BENZOLSULFONYL) -N-METHYL- 2-AMINOMETHYL-2-METHYL-TETRAHYDROFURANE |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2033382A true GB2033382A (en) | 1980-05-21 |
| GB2033382B GB2033382B (en) | 1982-11-03 |
Family
ID=6051240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7933926A Expired GB2033382B (en) | 1978-10-03 | 1979-10-01 | Production of n - (4' - chloro - 3 - sulphamoylbenzenesulphonyl) - n methyl - 2 - aminomethyl- 2 - methyl tetrahydrofurane |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS5942674B2 (en) |
| CH (1) | CH641174A5 (en) |
| DE (1) | DE2843040A1 (en) |
| GB (1) | GB2033382B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4503131A (en) * | 1982-01-18 | 1985-03-05 | Richardson Chemical Company | Electrical contact materials |
| JPS59812A (en) * | 1982-06-28 | 1984-01-06 | 田中貴金属工業株式会社 | Brush material for sliding contacts |
| JPS59219818A (en) * | 1983-05-27 | 1984-12-11 | 田中貴金属工業株式会社 | Composite electric contact material |
-
1978
- 1978-10-03 DE DE19782843040 patent/DE2843040A1/en active Granted
-
1979
- 1979-10-01 GB GB7933926A patent/GB2033382B/en not_active Expired
- 1979-10-01 CH CH880379A patent/CH641174A5/en not_active IP Right Cessation
- 1979-10-02 JP JP12648079A patent/JPS5942674B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5549367A (en) | 1980-04-09 |
| GB2033382B (en) | 1982-11-03 |
| DE2843040A1 (en) | 1980-04-17 |
| JPS5942674B2 (en) | 1984-10-16 |
| CH641174A5 (en) | 1984-02-15 |
| DE2843040C2 (en) | 1988-02-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |