DE1185194B - Process for the production of clumps of salicylic acid amide - Google Patents

Process for the production of clumps of salicylic acid amide

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Publication number
DE1185194B
DE1185194B DEN18252A DEN0018252A DE1185194B DE 1185194 B DE1185194 B DE 1185194B DE N18252 A DEN18252 A DE N18252A DE N0018252 A DEN0018252 A DE N0018252A DE 1185194 B DE1185194 B DE 1185194B
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Germany
Prior art keywords
radical
amide
general formula
compound
production
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.)
Pending
Application number
DEN18252A
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German (de)
Inventor
Torizo Takahashi
Kikuo Ogiu
Hajime Fujimura
Isao Satoda
Tomijiro Fukui
Yasuo Yamamoto
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Nippon Shinyaku Co Ltd
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Nippon Shinyaku Co Ltd
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Publication of DE1185194B publication Critical patent/DE1185194B/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/60—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups

Description

BUNDESREPUBLIK DEUTSCHLANDFEDERAL REPUBLIC OF GERMANY

Internat. Kl.: C 07 cBoarding school Class: C 07 c

DEUTSCHESGERMAN

PATENTAMTPATENT OFFICE

AUSLEGESCHRIFTEDITORIAL

C07dC07d

Deutschem.: 12 q-6/01 German: 12 q- 6/01

Nummer: 1185Number: 1185

Aktenzeichen: N 18252IV b/12 qFile number: N 18252IV b / 12 q

Anmeldetag: 29. April 1960 Filing date: April 29, 1960

Auslegetag: 14. Januar 1965Opening day: January 14, 1965

Die Erfindung betrifft ein Verfahren zur Herstellung von Abkömmlingen des Salicylsäureamides der allgemeinen Formel IThe invention relates to a process for the preparation of derivatives of salicylic acid amide of the general formula I.

— CO — N — CH — COB- CO - N - CH - COB

(I)(I)

in der R1 einen Alkoxy- oder Benzyloxyrest, R2 Wasserstoff, Alkyl, Phenyl oder einen Alkoxyphenylrest, R3 Wasserstoff oder Alkyl und B einen Alkoxyrest oder die Gruppe — NRR' bedeutet, wobei R und R' gleich oder unterschiedlich sind und Wasserstoff oder einen Alkylrest bedeuten oder R und R' mit dem Stickstoffatom einen Ring bilden.in which R 1 is an alkoxy or benzyloxy radical, R 2 is hydrogen, alkyl, phenyl or an alkoxyphenyl radical, R 3 is hydrogen or alkyl and B is an alkoxy radical or the group - NRR ', where R and R' are the same or different and are hydrogen or denote an alkyl radical or R and R 'form a ring with the nitrogen atom.

Die nach dem erfindungsgemäßen Verfahren herstellbaren Verbindungen sind neu und noch nicht in der Literatur beschrieben worden. Dieselben besitzen ausgezeichnete antipyretische, analgetische und antiphlogistische Wirkungen, wobei die analgetische Wirksamkeit besonders ausgeprägt ist. Einige dieser Verbindungen besitzen eine gute Wasserlöslichkeit, und ihre Lösungen sind zweckmäßig als Injektionslösung verwendbar.The compounds which can be prepared by the process according to the invention are new and not yet in use has been described in the literature. They have excellent antipyretic, analgesic and antiphlogistic Effects, whereby the analgesic effectiveness is particularly pronounced. Some of these Compounds have good water solubility and their solutions are useful as a solution for injection usable.

Der Nachweis der Überlegenheit der erfindungsgemäß hergestellten Verbindungen gegenüber dem Verfahren zur Herstellung von Abkömmlingen des SalicylsäureamidesProof of the superiority of the compounds prepared according to the invention over the Process for the preparation of derivatives of salicylic acid amide

Anmelder:Applicant:

Nippon Shinyaku Co. Limited, Kyoto (Japan) Vertreter:Nippon Shinyaku Co. Limited, Kyoto (Japan) Representative:

Dipl.-Ing. A. Kuhn, Patentanwalt, Berlin 33, Wildpfad 3Dipl.-Ing. A. Kuhn, patent attorney, Berlin 33, Wildpfad 3

Als Erfinder benannt:Named as inventor:

Torizo Takahashi, Kikuo Ogiu,Torizo Takahashi, Kikuo Ogiu,

Hajime Fujimura, Isao Satoda,Hajime Fujimura, Isao Satoda,

Tomijiro Fukui, Yasuo Yamamoto, Kyoto (Japan)Tomijiro Fukui, Yasuo Yamamoto, Kyoto (Japan)

Beanspruchte Priorität:Claimed priority:

Japan vom 29. Januar 1960 (2736)Japan January 29, 1960 (2736)

bekannten Procain-Coffein-Komplex wird durch die folgenden vergleichenden Zahlenwerte erbracht.known procaine-caffeine complex is provided by the following comparative numerical values.

Verbindunglink LD50 1 LD 50 1 ED60 2 ED 60 2 Index3 Index 3 O-CH3O — C8H4 — CONHCH2CON(CH3)2 O-CH3O - C 8 H 4 - CONHCH 2 CON (CH 3) 2 8,68.6 0,80.8 10,410.4 (Beispiel 4)(Example 4) OsCH3O — C6H4 — CONHCH2CON(CH3)2 OsCH 3 O - C 6 H 4 - CONHCH 2 CON (CH 3 ) 2 6,566.56 1,451.45 4,524.52 (Beispiel 8)(Example 8) O-CH3O — C6H4 — CON(C6H5)CH2CON(CH3)2 ....O-CH3O - C 6 H 4 - CON (C 6 H 5 ) CH 2 CON (CH 3 ) 2 .... 3,183.18 1,51.5 2,122.12 (Beispiel 9)(Example 9) Procain-Coffein-Komplex Procaine-Caffeine Complex 3,063.06 >2,0> 2.0 < 1,03 < 1.03

1 (in 10g/mg intraperitonal) gemessen nach dem Verfahren von Witchfield — Wilcoxon nach der Verabreichung dei Droge an Mäuse der dd-Abstammung (12 bis 13 Körpergewicht), modifiziert nach dem Verfahren von H äff η er. a (in 10 g/mg intraperitonal) berechnet aus Zahlen werten gestorbener Mäuse 24 Stunden nach der Verabreichung der Droge. 1 (in 10g / mg intraperitoneally) measured according to the method of Witchfield - Wilcoxon after administration of the drug to mice of dd parentage (12 to 13 body weight), modified according to the method of Haff η er. a (in 10 g / mg intraperitoneally) calculated from numbers of dead mice 24 hours after administration of the drug.

Erfindungsgemäß werden die gewünschten Ver- dargestellt werden, mit einer Verbindung der allbindungen durch Umsetzung von substituierter Benzoe- gemeinen Formel III säure oder deren funktionellen Abkömmlingen, die 45 NH — CH — COBAccording to the invention, the desired representations will be shown with a connection of the all connections by reacting substituted benzoin common formula III acid or its functional derivatives, the 45 NH - CH - COB

durch die allgemeine Formel IIby the general formula II

-— COOH- COOH

(Π)(Π)

: (in): (in)

R2 R3R2 R3

erhalten. Gegebenenfalls kann die hierbei resultierende Verbindung mit Aminen der allgemeinen Formel IVobtain. The resulting compound can optionally be mixed with amines of the general formula IV

HNRR' (IV)HNRR '(IV)

behandelt werden, wenn B ein Alkoxyrest ist.be treated when B is alkoxy.

409 768/387409 768/387

Bezüglich der funktioneilen Abkömmlinge der Säure können Abkömmlinge, wie Ester, Säureanhydride, Säurehalogenide usw., angewandt werden. Im allgemeinen werden jedoch bevorzugt die Säurehalogenide angewandt. In diesem Fall ist es vorteilhaft, organische Lösungsmittel, wie Chloroform, Benzol, in Gegenwart eines säurebindenden Mittels, wie Kaliumcarbonat, anzuwenden. Für den Fall, daß ein Säureester als Ausgangsverbindung angewandt wird, ist es vorteilhaft, eine geringe Menge Natriumalkoholat zuzusetzen und zu erwärmen.Regarding the functional derivatives of the acid derivatives such as esters, acid anhydrides, acid halides, etc. can be used. In general however, the acid halides are preferably used. In this case it is beneficial to use organic Solvents such as chloroform, benzene, in the presence of an acid-binding agent such as potassium carbonate, apply. In the event that an acid ester is used as the starting compound, it is advantageous add a small amount of sodium alcoholate and heat.

Beispiel 1example 1

Herstellung von N-2-Methoxybenzoyl-N'-methylglycinamid Preparation of N-2-methoxybenzoyl-N'-methylglycine amide

In ein gekühltes und gerührtes Gemisch aus 2,4 g N-Methylglycinamid, 4,3 g Kaliumcarbonat und 20 ml Chloroform wird eine Lösung aus 5 g frisch hergestelltem 2-Methoxybenzoylchlorid in 10 ml Chloroform eingetropft, sodann 1,5 Stunden lang am Rück- ao fluß gehalten, filtriert und das Filtrat von dem Methanol befreit. Es werden hierbei 4,2 g der oben angegebenen Verbindung mit einem Fp. = 98 bis 99°C erhalten.In a cooled and stirred mixture of 2.4 g of N-methylglycine amide, 4.3 g of potassium carbonate and 20 ml Chloroform is a solution of 5 g of freshly prepared 2-methoxybenzoyl chloride in 10 ml of chloroform added dropwise, then kept under reflux for 1.5 hours ao, filtered and the filtrate from the Methanol freed. There are 4.2 g of the above compound with a melting point = 98 to 99 ° C obtained.

Analyse für C11H14O5N2 (222,24): Berechnet .... C 59,45%, H 6,35%, N 12,60%. gefunden .... C 59,55%, H 6,33%, N 12,42%.Analysis for C 11 H 14 O 5 N 2 (222.24): Calculated .... C 59.45%, H 6.35%, N 12.60%. found .... C 59.55%, H 6.33%, N 12.42%.

Beispiel2Example2

Herstellung von N-2-MethoxybenzoylglycinamidPreparation of N-2-methoxybenzoylglycine amide

Wie im Beispiel 1 angegeben, werden 1,8 g Glycinamid mit 5 g 2-Methoxybenzoylchlorid umgesetzt, wobei 3,1 g der oben angegebenen Verbindung mit einem Fp. == 150 bis 1510C erhalten werden.As indicated in Example 1, 1.8 g of glycine amide are reacted with 5 g of 2-methoxybenzoyl chloride, 3.1 g of the above-mentioned compound having a melting point of 150 to 151 ° C. being obtained.

Analyse für C10H12O3N2 (208,21):
Berechnet .... C 57,68%, H 5,81 %, N 13,46%; gefunden .... C 57,70%, H 5,92%, N 13,39%·Analysis for C 10 H 12 O 3 N 2 (208.21):
Calculated .... C 57.68%, H 5.81%, N 13.46%; found .... C 57.70%, H 5.92%, N 13.39%

Beispiel 3Example 3

Herstellung vonN-2-Methoxybenzoylglycinäthylester Preparation of N-2-methoxybenzoylglycine ethyl ester

Es werden 10 g Glycinäthylester in 50 ml Chloroform gelöst, Kaliumcarbonat zugesetzt und 17 g 2-Methoxybenzoylchlorid unter Eiskühlung und Rühren zugesetzt. Sodann wird 2 Stunden am Rückfluß gekocht, Wasser zugesetzt und die abgetrennte Chloroformschicht getrocknet, eingeengt und unter verringertem Druck destilliert. Hierdurch werden 20 g entsprechend einer 85%igen Ausbeute der oben angegebenen Verbindung mit einem Sdp. = 162°C/1 mm Hg erhalten.10 g of glycine ethyl ester are dissolved in 50 ml of chloroform, potassium carbonate is added and 17 g 2-methoxybenzoyl chloride was added with ice-cooling and stirring. It is then refluxed for 2 hours boiled, water added and the separated chloroform layer dried, concentrated and under distilled under reduced pressure. As a result, 20 g corresponding to an 85% yield of the above are obtained Compound with a bp = 162 ° C / 1 mm Hg obtained.

Analyse für C12H15O4N2 (237,35):Analysis for C 12 H 15 O 4 N 2 (237.35):

Berechnet C 60,75%, H 6,37%, N 5,90%;Calculated C 60.75%, H 6.37%, N 5.90%;

gefunden C 60,62%, H 6,45%, N 5,75%.found C 60.62%, H 6.45%, N 5.75%.

Beispiel 4Example 4

Herstellung von N-2-Methoxybenzoyl-Ν',Ν'-dimethylglycinamid Production of N-2-methoxybenzoyl-Ν ', Ν'-dimethylglycine amide

(a) Es werden 3 g N-2-Methoxybenzoylglycinäthylester in 3 ml Äthanol gelöst und 7,5 ml einer 40%igen wäßrigen Lösung von Dimethylamin unter Eiskühlung und Rühren zugesetzt. Es wird weitere 2 Stunden gerührt und mit Kaliumcarbonat ausgesalzen. Durch Extraktion mit Chloroform werden 2,3 g der oben(a) There are 3 g of N-2-methoxybenzoylglycine ethyl ester dissolved in 3 ml of ethanol and 7.5 ml of a 40% strength aqueous solution of dimethylamine with ice cooling and stirring added. It is stirred for a further 2 hours and salted out with potassium carbonate. By Extraction with chloroform will be 2.3 g of the above

6o angegebenen Verbindung in Form von Nadeln mit einem Fp. = 118° C (η-Hexan—Äthanol) erhalten. 6o indicated compound in the form of needles with a melting point = 118 ° C (η-hexane-ethanol).

Analyse für C12H16O3N3 (236,25):Analysis for C 12 H 16 O 3 N 3 (236.25):

Berechnet .... C 61,00%, H 6,83%, N 11,86%; gefunden .... C 61,16%, H 6,95%, N 11,66%.Calculated .... C 61.00%, H 6.83%, N 11.86%; found .... C 61.16%, H 6.95%, N 11.66%.

(b) Zu einem eisgekühlten und gerührten Gemisch aus 3 g N', N'-Dimethylglycinamid, 4,3 g Kaliumcarbonat und 20 ml Chloroform wird eine Lösung von 5,3 g 2-Methoxybenzoylchlorid in Chloroform gegeben, 1,5 Stunden erwärmt und Wasser zugesetzt. Aus der Chloroformschicht wird die obige Verbindung in Form von Nadeln in einer Menge von 6,7 g mit einem Fp. = 117 bis 1180C (η-Hexan—Äthanol) erhalten.(b) A solution of 5.3 g of 2-methoxybenzoyl chloride in chloroform is added to an ice-cooled and stirred mixture of 3 g of N ', N'-dimethylglycine amide, 4.3 g of potassium carbonate and 20 ml of chloroform, the mixture is heated for 1.5 hours and Water added. The above compound is obtained from the chloroform layer in the form of needles in an amount of 6.7 g with a melting point = 117 to 118 ° C. (η-hexane — ethanol).

(c) Die obige Verbindung wird ebenfalls durch Umsetzung von 3,1 g N', N'-Dimethylglycinamid und 5 g 2-Methoxybenzoesäuremethylester in einer Ausbeute von 1,2 g erhalten. Die Verbindung zeigte einen Fp. = 117 bis 118°C.(c) The above compound is also obtained by reacting 3.1 g of N ', N'-dimethylglycine amide and 5 g of methyl 2-methoxybenzoate were obtained in a yield of 1.2 g. The connection showed mp = 117 to 118 ° C.

Beispiel 5Example 5

Herstellung von N-2-Methoxybenzoyl-Ν',Ν'-diäthylglycinamid Production of N-2-methoxybenzoyl-Ν ', Ν'-diethylglycine amide

Ein Gemisch aus 3 g 2-Methoxybenzoylglycinäthylester, 3 ml Äthanol und 100 ml Wasser wird in der gleichen Weise wie im Beispiel 4, (a) mit 4 g Diäthylamin umgesetzt, wodurch eine ölige Verbindung in einer Ausbeute von 2,8 g erhalten wird. Diese Verbindung weist einen Sdp. = 207 bis 204° C/l mm Hg auf.A mixture of 3 g of 2-methoxybenzoylglycine ethyl ester, 3 ml of ethanol and 100 ml of water are made in the same manner as in Example 4, (a) with 4 g of diethylamine reacted, whereby an oily compound is obtained in a yield of 2.8 g. This connection has a bp = 207 to 204 ° C / l mm Hg.

Analyse für C14H20O3N2 (264,32):
Berechnet .... C 63,61 %, H 7,63 %, N 10,60%; gefunden .... C 63,42%, H 7,84%, N 10,55%.Analysis for C 14 H 20 O 3 N 2 (264.32):
Calculated .... C 63.61%, H 7.63%, N 10.60%; found .... C 63.42%, H 7.84%, N 10.55%.

Beispiel 6Example 6

Herstellung von N-2-Methoxybenzoylglycinpiperidid Preparation of N-2-methoxybenzoylglycine piperidide

Durch Umsetzung von 2 g 2-MethoxybenzoylgIycinäthylester und 5 g Piperidin wird die oben angegebene Verbindung in einer Menge von 4,8 g mit einem Fp. = 90 bis 98 0C erhalten.The above mentioned compound is g in an amount of 4.8 to 98 = 90 0 C obtained with a mp., By reacting 2 g of 2-MethoxybenzoylgIycinäthylester and 5 g of piperidine.

Analyse für C15H20O3N2 (276,33):
Berechnet .... C 65,19%, H 7,30%, N 10,14%; gefunden .... C 65,00%, H 7,41 %, N 10,33%.Analysis for C 15 H 20 O 3 N 2 (276.33):
Calculated .... C 65.19%, H 7.30%, N 10.14%; found .... C 65.00%, H 7.41%, N 10.33%.

B ei spiel 7 -<<Eg game 7 - <<

Herstellung von N-2-Äthoxybenzoyl-N', N'-dimethylglycinamidPreparation of N-2-ethoxybenzoyl-N ', N'-dimethylglycine amide

Durch Umsetzung von 5,5 g 2-Äthoxybenzoylchlorid und 3 g N', N'-Dimethylglycinamid, wie im Beispiel 1 beschrieben, wird die obige Verbindung in Form von Nadeln mit einem Fp. = 125 bis 126 0C in einer Ausbeute von 6,3 g erhalten.By reacting 5.5 g of 2-ethoxybenzoyl chloride and 3 g of N ', N'-dimethylglycine amide, as described in Example 1, the above compound is obtained in the form of needles with a melting point = 125 to 126 ° C. in a yield of 6 , 3 g obtained.

Analyse für C13H18O3N2 (250,29):Analysis for C 13 H 18 O 3 N 2 (250.29):

Berechnet .... C 62,38 %, H 7,25%, N 11,19%; gefunden .... C 62,05%, H 7,19%, N 11,07%.Calculated .... C 62.38%, H 7.25%, N 11.19%; found .... C 62.05%, H 7.19%, N 11.07%.

Beispiel 8Example 8

Herstellung von N-2-Benzyloxybenzoyl-N', N'-dimethylglycinamidProduction of N-2-Benzyloxybenzoyl-N ', N'-dimethylglycine amide

Durch Umsetzung von 6,1 g 2-Benzyloxybenzoylchlorid und 2,6 g N', N'-Dimethylglycinamid, wie im Beispiel 1 beschrieben, wird die oben angegebeneBy reacting 6.1 g of 2-benzyloxybenzoyl chloride and 2.6 g of N ', N'-dimethylglycine amide, as described in Example 1, becomes that given above

Verbindung in Form von Nadeln mit einem Fp. = 123 bis 1243C in einer Ausbeute von 5,8 g erhalten.Compound in the form of needles with a m.p. = 123 to 124 3 C was obtained in a yield of 5.8 g.

Analyse für C18H20O3N2 (312,36):Analysis for C 18 H 20 O 3 N 2 (312.36):

Berechnet C 69,21 %, H 6,45%, N 8,97%; ,Calculated C 69.21%, H 6.45%, N 8.97%; ,

gefunden C 69,36%, H 6,60%, N 8,88%.found C 69.36%, H 6.60%, N 8.88%.

Beispiel 9Example 9

Herstellung von N-2-Methoxybenzoyl-N-phenyl-Production of N-2-methoxybenzoyl-N-phenyl-

N', N'-dimethylglycinamidN ', N'-dimethylglycine amide

Durch Umsetzung von 10 g 2-Methoxybenzoylchlorid und 10 g N-Phenyl-N', N'-dimethylglycinamid, wie im Beispiel 1 beschrieben, wird die oben angegebene Verbindung mit einem Fp. = 112 bis 113° C in einer Ausbeute von 13,7 g erhalten.By reacting 10 g of 2-methoxybenzoyl chloride and 10 g of N-phenyl-N ', N'-dimethylglycine amide, as described in Example 1, the compound given above with a melting point = 112 to 113 ° C obtained in a yield of 13.7 g.

Analyse für C18H20O3N2 (312,36):Analysis for C 18 H 20 O 3 N 2 (312.36):

Berechnet C 69,21 %, H 6,45 %, N 8,97 %;Calculated C 69.21%, H 6.45%, N 8.97%;

gefunden C 69,33%, H 6,44%, N 8,99%.found C 69.33%, H 6.44%, N 8.99%.

Beispiel 10Example 10

Herstellung von N-2-Methoxybenzoyl-N-methyl-N', N'-dimethylglycinamidProduction of N-2-methoxybenzoyl-N-methyl-N ', N'-dimethylglycine amide

Es werden 8,5 g 2-Methoxybenzoylchlorid mit 5 g N-Methyl-N', N'-dimethylglycinamid in der gleichen Weise umgesetzt, wie im Beispiel 1 angegeben. Man erhält die oben angegebene Verbindung mit einem Fp. = 99°C in einer Menge von 7,5 g.There are 8.5 g of 2-methoxybenzoyl chloride with 5 g of N-methyl-N ', N'-dimethylglycine amide in the same Way implemented as indicated in Example 1. The compound given above is obtained with a Mp = 99 ° C in an amount of 7.5 g.

Analyse für C13H18O3N2 (250,29): Berechnet .... C 62,38%, H 7,25%, N 11,19%; gefunden .... C 62,47%, H 7,25%, N 11,07%.Analysis for C 13 H 18 O 3 N 2 (250.29): Calculated .... C 62.38%, H 7.25%, N 11.19%; found .... C 62.47%, H 7.25%, N 11.07%.

Beispiel 11Example 11

Herstellung von N-2-Methoxybenzoyl-N-methyl-N', N'-diäthylglycinamidProduction of N-2-methoxybenzoyl-N-methyl-N ', N'-diethylglycine amide

Es werden 5,8 g 2-Methoxybenzoylchlorid mit 5 g N-Methyl-N', N'-diäthylglycinamid in der gleichen Weise umgesetzt, wie im Beispiel 1 angegeben, wodurch die oben angegebene Verbindung mit einem Sdp. = 195 bis 198°C/1 bis 2 mm Hg in einer Ausbeute von 7,0 g erhalten wird.There are 5.8 g of 2-methoxybenzoyl chloride with 5 g of N-methyl-N ', N'-diethylglycine amide in the same Way implemented as indicated in Example 1, whereby the above compound with a Bp = 195 to 198 ° C / 1 to 2 mm Hg is obtained in a yield of 7.0 g.

Analyse für C15H22O3N2 (278,34):Analysis for C 15 H 22 O 3 N 2 (278.34):

Berechnet N 10,07%;Calculated N 10.07%;

gefunden N 10,11%.found N 10.11%.

Weise umgesetzt, wie im Beispiel 1 angegeben, wodurch die obige Verbindung mit einem Sdp. = 175 bis 178°C/1 bis 2 mm Hg in einer Ausbeute von 3,6 g erhalten wird.Way implemented as indicated in Example 1, whereby the above compound with a bp = 175 to 178 ° C / 1 to 2 mm Hg is obtained in a yield of 3.6 g.

Analyse für C14H20O3N2 (264,32):Analysis for C 14 H 20 O 3 N 2 (264.32):

Berechnet N 10,60%;Calculated N 10.60%;

gefunden .... N 10,52%.found .... N 10.52%.

Claims (1)

Patentanspruch:Claim: Verfahren zur Herstellung von Abkömmlingen des Salicylsäureamides der allgemeinen Formel IProcess for the preparation of derivatives of the salicylic acid amide of the general formula I. -CO-N —CH-COB (I)
I
R2 R3 -CO-N -CH-COB (I)
I.
R2 R3 in der R1 einen Alkoxy- oder Benzyloxyrest, R2 Wasserstoff, Alkyl, Phenyl oder einen Alkoxyphenylrest, R3 Wasserstoff oder Alkyl und B einen Alkoxyrest oder die Gruppe —NRR' bedeutet, wobei R und R' gleich oder unterschiedlich sind und Wasserstoff oder einen Alkylrest bedeuten oder R und R' mit dem Stickstoffatom einen Ring bilden, dadurch gekennzeichnet, daß man eine Verbindung der allgemeinen Formel IIin which R 1 is an alkoxy or benzyloxy radical, R 2 is hydrogen, alkyl, phenyl or an alkoxyphenyl radical, R 3 is hydrogen or alkyl and B is an alkoxy radical or the group —NRR ', where R and R' are the same or different and are hydrogen or denote an alkyl radical or R and R 'form a ring with the nitrogen atom, characterized in that a compound of the general formula II 3535 4545 Beispiel 12Example 12 Herstellung von N-Methoxybenzoyl-N-methyl-N', N'-dimethylalaninamidProduction of N-methoxybenzoyl-N-methyl-N ', N'-dimethylalanine amide Es werden 3 g 2-Methoxybenzoylchlorid mit 2,4 g N-Methyl-N', N'-dimethylalaninamid in der gleichenThere are 3 g of 2-methoxybenzoyl chloride with 2.4 g of N-methyl-N ', N'-dimethylalaninamide in the same -COOH-COOH (Π)(Π) oder deren funktionell Abkömmlinge mit einer Verbindung der allgemeinen Formel IIIor their functional derivatives with a compound of the general formula III NH- CH-COBNH-CH-COB R2 R3R2 R3 umsetzt, wobei man in dem Fall, daß B einen Alkoxyrest bedeutet, das Reaktionsprodukt gegebenenfalls mit einem Amin der allgemeinen Formel IVreacted, in the case that B is an alkoxy radical, the reaction product is optionally with an amine of the general formula IV HNRR' (IV)HNRR '(IV) umsetzt.implements. In Betracht gezogene Druckschriften:
Deutsche Patentschrift Nr. 900 576;
Beilstein, Handbuch der organischen Chemie, 4. Auflage, Hptw. Bd. 9, S. 230; Ergw. I, Bd. 9, S. 45; Ergw. II, Bd. 9, S. 176.Considered publications:
German Patent No. 900 576;
Beilstein, Handbook of Organic Chemistry, 4th Edition, Hptw. Vol. 9, p. 230; Ergw. I, Vol. 9, p. 45; Ergw. II, Vol. 9, p. 176. 409 768/387 1.65 © Bundesdruckerei Berlin409 768/387 1.65 © Bundesdruckerei Berlin
DEN18252A 1959-06-11 1960-04-29 Process for the production of clumps of salicylic acid amide Pending DE1185194B (en)

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EP0206546A3 (en) * 1985-06-10 1987-09-02 American Home Products Corporation N-û(1-naphthalenyl)-thioxomethyl and carbonyl¨-n-methylglycinamide derivatives
WO2005077122A3 (en) * 2004-02-11 2005-12-29 Irm Llc Compounds and compositions as lxr modulators

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2851831A1 (en) * 1978-11-30 1980-06-19 Henkel Kgaa HAIR TREATMENT WITH ANTI-DUPLIC EFFECT
US5654301A (en) * 1985-02-15 1997-08-05 Research Corporation Technologies, Inc. Amino acid derivative anticonvulsant
US5378729A (en) * 1985-02-15 1995-01-03 Research Corporation Technologies, Inc. Amino acid derivative anticonvulsant
EP1284724B1 (en) * 2000-03-21 2012-04-18 Emisphere Technologies, Inc. Method of preparing alkylated salicylamides via a dicarboxylate intermediate

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DE900576C (en) * 1942-12-18 1953-12-28 Geigy Ag J R Process for the preparation of acylated aliphatic aminocarboxamides

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DE900576C (en) * 1942-12-18 1953-12-28 Geigy Ag J R Process for the preparation of acylated aliphatic aminocarboxamides

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0206546A3 (en) * 1985-06-10 1987-09-02 American Home Products Corporation N-û(1-naphthalenyl)-thioxomethyl and carbonyl¨-n-methylglycinamide derivatives
WO2005077122A3 (en) * 2004-02-11 2005-12-29 Irm Llc Compounds and compositions as lxr modulators
AU2005211807B2 (en) * 2004-02-11 2008-08-28 Irm Llc Compounds and compositions as LXR modulators
AU2005211807C1 (en) * 2004-02-11 2009-07-16 Irm Llc Compounds and compositions as LXR modulators
US7846949B2 (en) 2004-02-11 2010-12-07 Irm Llc Compounds and compositions as LXR modulators

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CH393355A (en) 1965-06-15
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