CA1037494A - Process for the preparation of n-(diethylaminoethyl)-2-methoxy-5-methylsulfonyl benzamide - Google Patents
Process for the preparation of n-(diethylaminoethyl)-2-methoxy-5-methylsulfonyl benzamideInfo
- Publication number
- CA1037494A CA1037494A CA208,496A CA208496A CA1037494A CA 1037494 A CA1037494 A CA 1037494A CA 208496 A CA208496 A CA 208496A CA 1037494 A CA1037494 A CA 1037494A
- Authority
- CA
- Canada
- Prior art keywords
- methoxy
- diethylaminoethyl
- nitrone
- methylsulfonylbenzaldehyde
- preparation
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C291/00—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00
- C07C291/02—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
A B S T R A C T
Process for preparing N-(diethylainoethyl)-2-methoxy-5-methylsulfonylbenzamide which comprises reacting 2-methoxy-5-methylsulfonylbenzaldehyde with N,N-diethylamino-ethylhydroxylamine to form the 2-methoxy-5-methylsulfonyl-benxaldehyde-(N,N-diethylaminoethyl)-nitrone And hydrolyzing the latter compound to form the desired benzamide which is useful as an antimetic and as an agent for modifying the digestive process.
Process for preparing N-(diethylainoethyl)-2-methoxy-5-methylsulfonylbenzamide which comprises reacting 2-methoxy-5-methylsulfonylbenzaldehyde with N,N-diethylamino-ethylhydroxylamine to form the 2-methoxy-5-methylsulfonyl-benxaldehyde-(N,N-diethylaminoethyl)-nitrone And hydrolyzing the latter compound to form the desired benzamide which is useful as an antimetic and as an agent for modifying the digestive process.
Description
1~37~9~
The present invention concerns a novel process for ~ .
the preparation of N-(diethylaminoethyl)-2-methoxy-5-methyl-sulfonylbenzamide (IV), its salts of addition with pharmaceuti- :cally acceptable mineral or organic acids, and the quaternary .:
ammonium salts produced by reacting said benzamide (IV~ with an alkylating agent.
The benzamide (IV) is produced by reacting 2-methoxy-; 5-methylsulfonylbenzaldehyde (I) with N,N-diethylaminnethyl-hydroxylamine (II), so as to produce 2-methoxy-5-methyl-sulfonylbenzaldehyde-(N,N-diethylaminoethyl)-nitrone (III) which is hydrolyzed by means of an acid to produce the desired :
benzamide (IV). ~.
This benzamide has attractive pharmacologlcal . properties as an antiemetic and as an agent for mod1fy~ng the digestive process. :;~
The diagram of the reaction is as follows:
The present invention concerns a novel process for ~ .
the preparation of N-(diethylaminoethyl)-2-methoxy-5-methyl-sulfonylbenzamide (IV), its salts of addition with pharmaceuti- :cally acceptable mineral or organic acids, and the quaternary .:
ammonium salts produced by reacting said benzamide (IV~ with an alkylating agent.
The benzamide (IV) is produced by reacting 2-methoxy-; 5-methylsulfonylbenzaldehyde (I) with N,N-diethylaminnethyl-hydroxylamine (II), so as to produce 2-methoxy-5-methyl-sulfonylbenzaldehyde-(N,N-diethylaminoethyl)-nitrone (III) which is hydrolyzed by means of an acid to produce the desired :
benzamide (IV). ~.
This benzamide has attractive pharmacologlcal . properties as an antiemetic and as an agent for mod1fy~ng the digestive process. :;~
The diagram of the reaction is as follows:
2 5~ N-CH2-CH2-Cl NH2H > 2 5 ~N-CH2-CH2- HoH
CHO 2 5/ R-CH2-CH2-RHOH CH-R-CH2-CH2-R~ 2 S
~ OCH3 ~ OCH3 H3CQ2S ~ (I~ H3CO2S ~ (III~
, O
CH N CH2 CH2 N~C H CO-NH-CH2-cH2-N~c H ~:
OCH3 ~ OC~13 hydrolYsi AS~ H3Co2s~J
(III) ~IV
~ ' ' '.
`, . . .
: ...... . , `. . . ~ ~ . .
~ 7~94 .
The following example illustrates but does not limit the present invention.
EXAMPLE I -~
N-(diethylaminoethyl)-2-methoxy-5-methylsulfonylbenzamide STAGE I: N?N-diethylaminoethylhydroxylamine Into a 1 litre balloon flask provided with a stirrer, a thermometer and a condenser there are introduced 41.7 g (0.6 mol) of hydroxylaminehydrochloride, 82.4 y (0.48 mol) oF
N,N-diethylamino-2-chloroethanehydrochloride, 86 g of sodium carbonate, 600 ml of 70% ethanol and 50 ml of water.
This is then heated For 8 hours under reflux, and left at rest overnight.
The alcohol is evaporated under vacuum and the product is extracted three times with 200 ml oF ether, aFter salting out the residue with potassium carbonate.
The organic phase is dried on potassium carbonate, and then filtered, and the ether is evaporated; the product is distilled under vacuum.
29 g (yield: 45%) of N,N-diethylaminoethylhydroxyl-amine is produced (boiling point/10 mm: 102-106C).
STAGE II: 2-methoxy-5-methylsulfonylbenzaldehyde-(N,N-diethyl-- aminoethyl)-nitrone 6.40 9 (0.03 mol) of 2-methoxy-5-methylsulfonyl- -; benzaldehyde, 3.96 g (0.03 mol) of N,N-diethylaminoethyl-hydroxylamine and 90 ml of dioxan are introduced into a 250 ml balloon flask provided with a stirrer, a thermometer and a condenser.
The mixture is heated under reflux For 5 hours, and left at rest For 2 days and then the solvent is evaporated under vacuum.
.~ ' :. .
1~ 94 -The residue is suspended in 20 ml of water and rendered alkaline with sodium hydroxide. The suspension is left to crystallize, and then filtration is effected. The crystallized substance is washed with water and dried in a drying oven at 50C.
5 g (yield: 50%) of 2-methoxy-5-methy1sulfonyl-benzaldehyde-(N,N-diethylaminoethyl)-nitrone (melting point:
110C) is produced.
STAGE III: N-(diethylaminoethyl)-2-methoxy-5-methylsulfonyl-benzamide :
5 g (0.015 mol) of 2-methoxy-5-methylsulfonyl-benzaldehyde-~N,N-diethylaminoethyl)-nitrone, 15 ml of acetic acid and 15 ml of acetic anhydr~de are placed in a 500 ml ;beaker. The m~xture is heated for 10 m~nutes to 80 - 90C.
Cooling is then effected, and then 50 ml of water and some 20%
sodiu~ hydroxide is added, until the pH-value is 10. The solution is left to crystallize, followed by filtration, washing with water and drying in a drying oven at 50C. The substance obtained is dissolved in 150 ml of ethanol and 20 hydrochloric ethanol is added until the pH-value is 1. The ;
solution is left to crystallize, followed by filtration, and then the product is washed with a little ethanol and dried in a drying oven at 50C.
2.5 9 (yield: 46%) of N-(diethylaminoethyl)-2-methoxy-5-methylsulfonylbenzamide hydrochloride(melting point:
199-200C) is produced.
: ' .
. .
CHO 2 5/ R-CH2-CH2-RHOH CH-R-CH2-CH2-R~ 2 S
~ OCH3 ~ OCH3 H3CQ2S ~ (I~ H3CO2S ~ (III~
, O
CH N CH2 CH2 N~C H CO-NH-CH2-cH2-N~c H ~:
OCH3 ~ OC~13 hydrolYsi AS~ H3Co2s~J
(III) ~IV
~ ' ' '.
`, . . .
: ...... . , `. . . ~ ~ . .
~ 7~94 .
The following example illustrates but does not limit the present invention.
EXAMPLE I -~
N-(diethylaminoethyl)-2-methoxy-5-methylsulfonylbenzamide STAGE I: N?N-diethylaminoethylhydroxylamine Into a 1 litre balloon flask provided with a stirrer, a thermometer and a condenser there are introduced 41.7 g (0.6 mol) of hydroxylaminehydrochloride, 82.4 y (0.48 mol) oF
N,N-diethylamino-2-chloroethanehydrochloride, 86 g of sodium carbonate, 600 ml of 70% ethanol and 50 ml of water.
This is then heated For 8 hours under reflux, and left at rest overnight.
The alcohol is evaporated under vacuum and the product is extracted three times with 200 ml oF ether, aFter salting out the residue with potassium carbonate.
The organic phase is dried on potassium carbonate, and then filtered, and the ether is evaporated; the product is distilled under vacuum.
29 g (yield: 45%) of N,N-diethylaminoethylhydroxyl-amine is produced (boiling point/10 mm: 102-106C).
STAGE II: 2-methoxy-5-methylsulfonylbenzaldehyde-(N,N-diethyl-- aminoethyl)-nitrone 6.40 9 (0.03 mol) of 2-methoxy-5-methylsulfonyl- -; benzaldehyde, 3.96 g (0.03 mol) of N,N-diethylaminoethyl-hydroxylamine and 90 ml of dioxan are introduced into a 250 ml balloon flask provided with a stirrer, a thermometer and a condenser.
The mixture is heated under reflux For 5 hours, and left at rest For 2 days and then the solvent is evaporated under vacuum.
.~ ' :. .
1~ 94 -The residue is suspended in 20 ml of water and rendered alkaline with sodium hydroxide. The suspension is left to crystallize, and then filtration is effected. The crystallized substance is washed with water and dried in a drying oven at 50C.
5 g (yield: 50%) of 2-methoxy-5-methy1sulfonyl-benzaldehyde-(N,N-diethylaminoethyl)-nitrone (melting point:
110C) is produced.
STAGE III: N-(diethylaminoethyl)-2-methoxy-5-methylsulfonyl-benzamide :
5 g (0.015 mol) of 2-methoxy-5-methylsulfonyl-benzaldehyde-~N,N-diethylaminoethyl)-nitrone, 15 ml of acetic acid and 15 ml of acetic anhydr~de are placed in a 500 ml ;beaker. The m~xture is heated for 10 m~nutes to 80 - 90C.
Cooling is then effected, and then 50 ml of water and some 20%
sodiu~ hydroxide is added, until the pH-value is 10. The solution is left to crystallize, followed by filtration, washing with water and drying in a drying oven at 50C. The substance obtained is dissolved in 150 ml of ethanol and 20 hydrochloric ethanol is added until the pH-value is 1. The ;
solution is left to crystallize, followed by filtration, and then the product is washed with a little ethanol and dried in a drying oven at 50C.
2.5 9 (yield: 46%) of N-(diethylaminoethyl)-2-methoxy-5-methylsulfonylbenzamide hydrochloride(melting point:
199-200C) is produced.
: ' .
. .
Claims (3)
1. A novel process for the preparation of the 2-methoxy-5-methylsulfonylbenzaldehyde-(N,N-diethylaminoethyl)-nitrone corresponding to the formula:
characterized in that 2-methoxy-5-methylsulfonylbenzaldehyde is reacted with N,N-diethylaminoethylhydroxylamine to produce the 2-methoxy-5-methylsulfonylbenzaldehyde-(N,N-diethylaminoethyl)-nitrone.
characterized in that 2-methoxy-5-methylsulfonylbenzaldehyde is reacted with N,N-diethylaminoethylhydroxylamine to produce the 2-methoxy-5-methylsulfonylbenzaldehyde-(N,N-diethylaminoethyl)-nitrone.
2. The process of Claim 1, wherein the nitrone compound obtained is hydrolyzed by means of an acid to produce the N-(diethylaminoethyl)-2-methoxy-5-methylsulfonylbenzamide.
3. 2-Methoxy-5-methylsulfonylbenzaldehyde-(N,N-diethylaminoethyl)-nitrone, when prepared by the process defined in Claim 1 or by an obvious chemical equivalent.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7332560A FR2243187B1 (en) | 1973-09-10 | 1973-09-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1037494A true CA1037494A (en) | 1978-08-29 |
Family
ID=9124839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA208,496A Expired CA1037494A (en) | 1973-09-10 | 1974-09-04 | Process for the preparation of n-(diethylaminoethyl)-2-methoxy-5-methylsulfonyl benzamide |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS5719102B2 (en) |
| AR (1) | AR205255A1 (en) |
| AT (1) | AT343096B (en) |
| CA (1) | CA1037494A (en) |
| DE (1) | DE2441451A1 (en) |
| ES (1) | ES429843A1 (en) |
| FI (1) | FI261574A (en) |
| FR (1) | FR2243187B1 (en) |
| GB (2) | GB1439296A (en) |
| IE (1) | IE39837B1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2528702A1 (en) * | 1982-06-17 | 1983-12-23 | Ile De France | APPLICATION OF N- (DIETHYLAMINOETHYL) 2-METHOXY-5-METHYLSULFONYL BENZAMIDE IN THE INHIBITION OF TRYPTOPHAN PYRROLASE |
| JPH0513801U (en) * | 1990-12-27 | 1993-02-23 | 哲夫 佐藤 | Bad road escaper |
| US20050182060A1 (en) * | 2004-02-13 | 2005-08-18 | Kelly Michael G. | 2-Substituted and 4-substituted aryl nitrone compounds |
-
1973
- 1973-09-10 FR FR7332560A patent/FR2243187B1/fr not_active Expired
-
1974
- 1974-01-01 AR AR254499D patent/AR205255A1/en active
- 1974-08-29 DE DE2441451A patent/DE2441451A1/en not_active Withdrawn
- 1974-09-04 GB GB121576A patent/GB1439296A/en not_active Expired
- 1974-09-04 CA CA208,496A patent/CA1037494A/en not_active Expired
- 1974-09-04 GB GB3872474A patent/GB1439295A/en not_active Expired
- 1974-09-06 FI FI2615/74A patent/FI261574A/fi unknown
- 1974-09-06 IE IE1861/74A patent/IE39837B1/en unknown
- 1974-09-06 ES ES429843A patent/ES429843A1/en not_active Expired
- 1974-09-09 AT AT722774A patent/AT343096B/en not_active IP Right Cessation
- 1974-09-09 JP JP10429474A patent/JPS5719102B2/ja not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB1439296A (en) | 1976-06-16 |
| DE2441451A1 (en) | 1975-03-13 |
| JPS5719102B2 (en) | 1982-04-20 |
| FI261574A (en) | 1975-03-11 |
| GB1439295A (en) | 1976-06-16 |
| IE39837L (en) | 1975-03-10 |
| IE39837B1 (en) | 1979-01-17 |
| FR2243187A1 (en) | 1975-04-04 |
| AR205255A1 (en) | 1976-04-21 |
| ES429843A1 (en) | 1976-10-01 |
| AT343096B (en) | 1978-05-10 |
| ATA722774A (en) | 1977-09-15 |
| JPS5053346A (en) | 1975-05-12 |
| FR2243187B1 (en) | 1978-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3032627B2 (en) | Method for producing 4-hydroxystyrene | |
| SU496719A3 (en) | Method for preparing dopamine derivatives | |
| SU606549A3 (en) | Method of preparing phenylalkylamines or salts thereof | |
| CA1037494A (en) | Process for the preparation of n-(diethylaminoethyl)-2-methoxy-5-methylsulfonyl benzamide | |
| US4002666A (en) | Process for the preparation of optically active p-hydroxyphenylglycine | |
| JPS5922711B2 (en) | Method for producing benzoxazolinone derivatives | |
| CN115572272B (en) | Preparation method of febuxostat and aldehyde ester intermediate thereof | |
| US4225721A (en) | Novel amidoxime derivatives | |
| US4393008A (en) | 2-Cyano-2-(3-phenoxy-phenyl)-propionic acid amide and preparation thereof | |
| US2490834A (en) | Benzhydryl beta hydroxy alkyl amines | |
| CA1039306A (en) | Preparation of optically active allethrolone via allethronyl acid phthalate | |
| US696020A (en) | Amidoöxybenzyl compound and process of making same. | |
| SU417938A3 (en) | METHOD OF OBTAINING 1- | |
| SU469681A1 (en) | The method of obtaining fluorinated diphenoxyacetic acids | |
| RU2155186C1 (en) | Method of preparing didecyl dimethyl ammonium bromide | |
| US2517496A (en) | Preparation of symmetrical monoaminodihydroxytoluene | |
| YU187290A (en) | PROCESS FOR THE PRODUCTION OF OPTICALLY ACTIVE 2- (TETRAHYDROPYRAN-2-YOLOXY) -1-PROPANO OL, A NEW INTERMEDIATE USED IN THIS PROCESS, AND ITS PREPARATION | |
| KR810001915B1 (en) | Process for preparing amino alkyl furan deriatives | |
| JPS62167754A (en) | Production of cyanomethylthioacetic acids | |
| KR810000198B1 (en) | Method for preparing ticrynafen | |
| Hopkins et al. | α-CYANO-β-ARYLACRYLIC ACIDS | |
| SU486503A3 (en) | Method for preparing β-phenyl fatty acid derivatives | |
| SU1191448A1 (en) | Method of producing n-benzyl-4-oxyquinolone-2 | |
| SU583128A1 (en) | Method of preparing 4-methoxy-n-methylnaphthalimide | |
| SU522794A3 (en) | Method for producing -1-phenoxy-2-hydroxy-3-aminopropane derivatives or their salts |