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MC1009A1 - New process for the preparation of N- (diethylaminoethyl) 2-methoxy-4-amino-5-chlrobenzamide - Google Patents

New process for the preparation of N- (diethylaminoethyl) 2-methoxy-4-amino-5-chlrobenzamide

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Publication number
MC1009A1
MC1009A1 MC1050A MC1050A MC1009A1 MC 1009 A1 MC1009 A1 MC 1009A1 MC 1050 A MC1050 A MC 1050A MC 1050 A MC1050 A MC 1050A MC 1009 A1 MC1009 A1 MC 1009A1
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MC
Monaco
Prior art keywords
methoxy
diethylaminoethyl
amino
preparation
new process
Prior art date
Application number
MC1050A
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French (fr)
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Soc Et Scient Et Ind De L Ile
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Soc Et Scient Et Ind De L Ile filed Critical Soc Et Scient Et Ind De L Ile
Publication of MC1009A1 publication Critical patent/MC1009A1/en

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Description

BREVET D'INVENTION PATENT FOR INVENTION

Déposé par la Société Anonyme dite : Filed by the public limited company known as:

SOCIETE D'ETUDES SCIENTIFIQUES ET INDUSTRIELLES DE L'ILE-DE-FRANCE SOCIETY FOR SCIENTIFIC AND INDUSTRIAL STUDIES OF ILE-DE-FRANCE

Ayant pour objet : Subject:

NOUVEAU PROCEDE DE PREPARATION DU N(DIETHYLAMINOETHYL) 2-METHOXY 4-AMINO 5-CHLOROBENZAMIDE NEW PROCESS FOR PREPARING N(DIETHYLAMINOETHYL) 2-METHOXY 4-AMINO 5-CHLOROBENZAMIDE

Priorité de la demande française : no. 72/23921, déposée le 30 juin 1972 Priority of the French application: no. 72/23921, filed on June 30, 1972

La présente invention concerne un nouveau procédé de préparation du N(diéthylaminoéthyl) 2-méthoxy 4-amino 5-chloro-benzamide (III), de ses sels d'addition avec des acides minéraux ou- organiques pharmaeeutiquemént acceptables, des sels d'ammonium quaternaires obtenus en faisant réagir ce benzamide (lll) avec un agent alcoylant. The present invention relates to a new process for preparing N(diethylaminoethyl) 2-methoxy 4-amino 5-chlorobenzamide (III), its addition salts with pharmaceutically acceptable mineral or organic acids, quaternary ammonium salts obtained by reacting this benzamide (III) with an alcoholic agent.

2 2

Le benzamide de la présente invention est obtenu en traitant l'acide 2-méthoxy 4-aminobenzolque (i) par la N, N diéthylaminoéthylènediamine en présence de chloroformiate d'éthyle pour obtenir le N(diéthylaminoéthyl) 2-méthoxy 4-aminobenzamide (il) et à chlorer ce composé par un chlorate alcalin pour obtenir le N(diéthylaminoéthyl) 2-méthoxy 4-amino 3-chlorobenzamide (III). The benzamide of the present invention is obtained by treating 2-methoxy 4-aminobenzol acid (i) with N,N diethylaminoethylenediamine in the presence of ethyl chloroformate to obtain N(diethylaminoethyl) 2-methoxy 4-aminobenzamide (il) and chlorinating this compound with an alkali chlorate to obtain N(diethylaminoethyl) 2-methoxy 4-amino 3-chlorobenzamide (III).

Le schéma de la réaction est le suivant : The reaction scheme is as follows:

10 10

15 15

COOH COOH

OCH. OCH.

'3 '3

HgNCHgCHgtT HgNCHgCHgtT

-C2H5 C2H5 -C2H5 C2H5

Ç0NHCH2CH N; Ç0NHCH2CH N;

OCH OCH

3 3

C2H5 C2H5 C2H5 C2H5

20 20

25 25

CONHCHgCHgN^ CONHCHgCHgN^

OCH- OCH-

■C2H5 C2H5 ■C2H5 C2H5

chlorate alcalin alkaline chlorate

C0NHCH2CH2N C0NHCH2CH2N

/C2H5 ^c2H5 /C2H5 ^c2H5

OCH OCH

3 3

30 30

35 35

L'exemple suivant illustre, sans la limiter, la présente invention. The following example illustrates, without limiting it, the present invention.

N(Diéthylaminoéthyl) 2-méthoxy 4-amino 5-chlorobenzamide STADB I : N(diéthylaminoéthyl) 2-méthoxy 4-aminobenzamide N(Diethylaminoethyl) 2-methoxy 4-amino 5-chlorobenzamide STADB I: N(diethylaminoethyl) 2-methoxy 4-aminobenzamide

Dans un ballon de 4 litres muni d'un agitateur mécanique, d'un thermomètre, d'un réfrigérant et d'une ampoule à brôme, on introduit 110 g (0,66 mol) d'acide 2-méthoxy 4-aminobenzolque, 2 litres de dioxanne et 92 ml de triéthylamine In a 4-liter round-bottom flask equipped with a mechanical stirrer, a thermometer, a condenser, and a bromine funnel, 110 g (0.66 mol) of 2-methoxy 4-aminobenzoic acid, 2 liters of dioxane, and 92 ml of triethylamine are introduced.

On agite dix minutes puis coule à température ambiante 72 g (0',66 mol) de chlorofonniate d'éthyle. Shake for ten minutes and then pour at room temperature 72 g (0.66 mol) of ethyl chlorofoniate.

On laisse agiter trente minutes et introduitj, en maintenant à température ambiante, 90 g (0,77 mol) de N, N 5 diéthylaminoéthylènediamine. We let it stir for thirty minutes and introduce, while maintaining at room temperature, 90 g (0.77 mol) of N,N 5 diethylaminoethylenediamine.

On agite ensuite trois heures* filtre et évapore le solvant sous vide. The mixture is then agitated for three hours*, filtered, and the solvent is evaporated under vacuum.

On ajoute 200 ml d'eau au résidu, 50 ml de soude à 40 et extrait avec 150 ml de chlorure de méthylène. La 10 solution organique séchée sur sulfate de magnésium, est filtrée - et évaporée à seo sous vide. 200 ml of water is added to the residue, along with 50 ml of sodium hydroxide solution at 40°C, and the mixture is extracted with 150 ml of methylene chloride. The resulting organic solution, dried over magnesium sulfate, is filtered and evaporated under vacuum.

On obtient 116 g de N(diéthylaminoéthyl) 2-méthoxy • 4-aminobenzamide (n $ ~ 1/5576) sous la forme d'une huile épaisse. 116 g of N(diethylaminoethyl) 2-methoxy • 4-aminobenzamide (n $ ~ 1/5576) is obtained in the form of a thick oil.

- 15 STADE II : N(diéthylaminoéthyl) 2-méthoxy 4-amino g-chloro-• benzamide - 15 STAGE II: N(diethylaminoethyl) 2-methoxy 4-amino g-chloro-• benzamide

Dans un ballon de 500 ml' muni d'un agitateur, d'un réfrigérant,, d'un thermomètre et d'une ampoule à brome, on introduit 16 g (0,06 mol) de N(diéthylaminoéthyl) 2-méthoxy 20 4-aminobenzamide, 60 ml d'acide acétique j, chauffe à 45 °C et verse 7,3 g d'anhydride acétique. In a 500 ml flask equipped with a stirrer, a condenser, a thermometer and a bromine ampoule, 16 g (0.06 mol) of N(diethylaminoethyl) 2-methoxy 20 4-aminobenzamide, 60 ml of acetic acid are introduced, heated to 45 °C and 7.3 g of acetic anhydride are added.

On laisse agiter quinze minutes à 45°C, refroidit et ajoute 18 ml d'acide ehlorhydrique à 30 $> en maintenant à température ambiante. On ajoute ensuite, goutte à goutte, en 25 maintenant à 20-25°C une solution de } g de chlorate de sodium dans 15 ml d'eau, laisse agiter quarante minutes, additionne 100 ml d'eau et la soude en quantité suffisante pour alcaliniser et saponifier. The mixture is stirred for fifteen minutes at 45°C, cooled, and 18 ml of 30% hydrochloric acid is added while maintaining room temperature. Then, a solution of 0 g of sodium chlorate in 15 ml of water is added dropwise while maintaining 20-25°C, stirred for forty minutes, and 100 ml of water and sufficient sodium hydroxide (lye) are added to alkalize and saponify.

On chauffe deux heures à reflux, refroidit, filtre 30 lave à l'eau, sèche à l'étuve à 50°C. We heat for two hours under reflux, cool, filter, wash with water, and dry in an oven at 50°C.

On obtient 14,5 S <3e N(diéthylaminoéthyl) 2-méthoxy -atnino 5-cklorobenzaraide (F ' 143-144°C). We obtain 14.5 S <3e N(diethylaminoethyl) 2-methoxy -atnino 5-chlorobenzaraide (F ' 143-144°C).

4 4

Claims (2)

REVENDICATIONSDEMANDS l).Nouveau procédé de préparation du N(diéthylaminoéthyl)l) New process for the preparation of N(diethylaminoethyl) 2-méthoxy 4»amino 5~ûhlorobenzamide répondant à la formule :2-methoxy 4-amino 5-hydroxychlorobenzamide corresponding to the formula: CONHCH CHN ^ pCONHCH CHN ^ p V°2H5 OCH-2 ^ p de ses sels d'addition avec des acides minéraux ou organiques pharmaceutiquement acceptables.„V°2H5 OCH-2 ^ p of its addition salts with pharmaceutically acceptable mineral or organic acids.„ de ses sels d'ammonium quaternaires,of its quaternary ammonium salts, caractérisé en ce que l'on fait réagir sur l'acide 2-méthoxy 4-aminobenzolque la N, N diéthylaminoéthylènediamine en présence de chloroformiate d'éthyle pour obtenir le N(diéthyl-amlnoéthyl) 2-méthoxy 4-aminobenzamide^ ce dernier composé étant traité par un chlorate alcalin pour obtenir le N(diéthyl aminoéthyl) 2-méthoxy 4-amino 5-chlorobenzamlde.characterized in that N,N-diethylaminoethylenediamine is reacted with 2-methoxy 4-aminobenzol acid in the presence of ethyl chloroformate to obtain N(diethyl-aminoethyl) 2-methoxy 4-aminobenzamide, the latter compound being treated with an alkali chlorate to obtain N(diethyl aminoethyl) 2-methoxy 4-amino 5-chlorobenzamide. 2) Procédé selon 1) dans lequel le chlorate alcalin utilisé est le chlorate de sodium.2) Process according to 1) in which the alkali chlorate used is sodium chlorate. reçwô\reçwô\ SOCIETE D'ETUDES SCIENTIFIQUES ET INDUSTRIELLES DE L'ILE-DE-FRANCESOCIETY FOR SCIENTIFIC AND INDUSTRIAL STUDIES OF ILE-DE-FRANCE LE MANDATAIRETHE AGENT îwo? n? n\t?V ni moV a\oo.W\îwo? n? n\t?V ni moV a\oo.W\ wn$wn$ J. EPURA\lJ. EPURA **
MC1050A 1972-06-30 1973-06-08 New process for the preparation of N- (diethylaminoethyl) 2-methoxy-4-amino-5-chlrobenzamide MC1009A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR7223921A FR2191552A5 (en) 1972-06-30 1972-06-30

Publications (1)

Publication Number Publication Date
MC1009A1 true MC1009A1 (en) 1974-10-18

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Family Applications (1)

Application Number Title Priority Date Filing Date
MC1050A MC1009A1 (en) 1972-06-30 1973-06-08 New process for the preparation of N- (diethylaminoethyl) 2-methoxy-4-amino-5-chlrobenzamide

Country Status (23)

Country Link
JP (1) JPS4962439A (en)
AT (1) AT336576B (en)
AU (1) AU468903B2 (en)
BE (1) BE801576A (en)
BG (1) BG21855A3 (en)
CA (1) CA992560A (en)
CH (1) CH580063A5 (en)
CS (1) CS167391B2 (en)
DD (1) DD107440A5 (en)
DE (1) DE2332719A1 (en)
ES (1) ES408019A1 (en)
FR (1) FR2191552A5 (en)
GB (1) GB1398373A (en)
HU (1) HU166937B (en)
IE (1) IE37853B1 (en)
IL (1) IL42610A (en)
LU (1) LU67899A1 (en)
MC (1) MC1009A1 (en)
PH (1) PH11627A (en)
RO (1) RO62646A2 (en)
SU (1) SU515444A3 (en)
YU (1) YU39020B (en)
ZA (1) ZA734435B (en)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1960130B2 (en) * 1968-12-02 1973-01-04 Yamanouchi Pharmaceutical Co. Ltd., Tokio Process for the preparation of N- (diethylaminoethyl) -4-amino-5-chloro-2methoxybenzamide

Also Published As

Publication number Publication date
FR2191552A5 (en) 1974-02-01
AU468903B2 (en) 1976-01-29
CH580063A5 (en) 1976-09-30
YU39020B (en) 1984-02-29
CS167391B2 (en) 1976-04-29
ES408019A1 (en) 1975-11-01
IL42610A0 (en) 1973-08-29
HU166937B (en) 1975-06-28
DD107440A5 (en) 1974-08-05
AU5748473A (en) 1975-01-09
JPS4962439A (en) 1974-06-17
AT336576B (en) 1977-05-10
BG21855A3 (en) 1976-09-20
LU67899A1 (en) 1974-08-19
PH11627A (en) 1978-04-12
YU176973A (en) 1982-02-28
IE37853L (en) 1973-12-30
IE37853B1 (en) 1977-10-26
SU515444A3 (en) 1976-05-25
ATA563673A (en) 1976-09-15
GB1398373A (en) 1975-06-18
RO62646A2 (en) 1978-02-15
ZA734435B (en) 1974-05-29
BE801576A (en) 1973-12-28
CA992560A (en) 1976-07-06
DE2332719A1 (en) 1974-01-10
IL42610A (en) 1976-03-31

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