DE1795110A1 - 2-alkoxy-4,5-azimidobenzamides and processes for their preparation - Google Patents

Description

PATfNTANWALTI DiPL-CHEM. DR. WERNER KOCH DR.-ING. RICHARD GLAWE DIPL-ING. KLAUS DELFS

HAMlURG

DIPL-PHYS. DR. WALTER MOLL

MONKS

2000 Hambarf 52 · Waltiitr ··· U · l «f ItH55 • 000 Mliich ·· 22 · Ll« bh «rrttra ·· 20 · I« f 22 (541

IHK ZBCHEN

THE NIGHT OF

OUR SIGN

MONKS

SOGIETE D ¹ ETUDES SCIEHTIPIQUES ET INDUSTRIELLES KB L'ILE-DE-PRANCE, Paris, France

2-alkoxy-4,5-a-imidobeneamides and processes for their preparation

The present invention relates to new 2-alkoxy-4,5-ai5iBiidobenzamides, their pharmaceutically acceptable Salae as well the process for the manufacture of these substances,

The benzainides according to the invention correspond to the general one Pormel,

COHH - (0H ₂ ) _n,. a

2098U / 1774

A dewatered a mono "odor bialkylaminoreate of the 3? Orrael

=> N "where the substituents R ₁ and Rg, which are the same as ^R 2

or can be different. Hydrogen or alkyl radicals with 1 - 5 carbon atoms mean. H ^ and Rg may form a ring with or without nitrogen, oxygen or sulfur verbunden.sein, the ring contains a nitrogen atom, then the latter can by an alkyl group with 1-5 carbon atoms may be substituted ₀ The rings formed in this way are for example the following : Pyrrolidinyl, Piperldinyl, Imidaaolidinyl _f Piperasino, ThI-aeolidinyl, H ~ methyl-pyxrolldinyl and N-ethylpiperidinyl,

A can also be a heterocyclic radical of the formula

Leg in which

R stands for an alkyl radical with 1-5 carbon atoms, m is a ganae number with a value less than 4.

B can be an alkyl or allcenyl radical with 1-5 carbon atoms be while

η is 1 or 2.

209814/1774

The following pharmaceutically acceptable salts of the bases described above can be:

Addition salts with a mineral acid, for example hydrochloric acid. Hydrobromic acid, phosphoric acid or an organic acid such as Z ₀ B ₀ gitroneneäure * tartaric acid, lactic acid or acetic acid, or quaternary © AinzaoniumEalzej, which are obtained by _r that the bases described above with an aliphatic or aromatic Alkylierungeaittelj such as methylene chloride »Methylhroiaid _t dimethylsulfate , p- # ethyltoriucloulfenate or the like uoge-.set ",

The compounds of the invention are interesting phay " malcological properties and can be particularly antiemetic Gowns, epaemogenic gowns, or analgesic agents be used" . |

Since the compounds according to the invention are one or more have asymmetrical Konienstoffatome, also fall the Rotating and counter-clockwise enormous amounts within the framework of the present » the invention,

The process according to the invention for the preparation of these compounds consists mainly in using a substituted 2-alkoxy? »

2 0981A / 177

Treat 4,5-aminobenzainide with a metal nitrile in an acidic medium. The metal nitrites used can be, for example, alkali metal nitrites, for example narittanitrite. Potassium = nitrite or the like _o The metal nitrites can be replaced by "another nitrosating agent such as amyl nitride".

The following examples explain the preparation of compounds according to the invention Connections “You should, however, the invention not restrict.

Example I ₁

ΙΓ7 (diethylaminoethyl ) -gn te thoyy ^ 4 ₁

Level A -

223 g (1 mol) of methyl 2-methoxy-4-acetaminobemsoate, 550 ml of acetic acid and 337 g of acetic anhydride are placed in a 2 liter flask equipped with a stirrer, a Shermometar W and a dropping funnel about 40 ⁰ C is heated to give a clear Lorning ₀ is obtained Sann is at 15 - 20 abgelriihlt ⁰ C followed by the dropwise by means of the Iropftriohters 106 g (1 mole + a 50 #iger excess) of nitric acid (d «1.49) augeββtat werdenο After the addition of nitric acid is complete, the mixture is stirred for another 1/2 hour at 40 ° C., after which it is cooled and the reaction mixture in 5

209814/1774

■ - 5 '- ■

Water is poured.

182 g (yield = * 68 $) MQthyl ~ 2 = metIiO3cy <= 4'-aostai2ino-5-aitrobenzoate (P ₁ , 163-165 ° O) are obtained.

Stage B - H »(Piäthylgu ^

182 g (0.68 mol) of methyl (0.68 mol χ 3) Diethylaminoiithylamin are added "The reaction is slightly exothermic ( ¹ JB ⁰ « 31 ⁰ G) ₀ One obtains a Supen = sion, which is heated to 55 ⁰ C, "which is 3/4 hour everything, whereupon 1/2 hour later the formation of a heavy precipitate is observed.

The reaction mixture is held at 55 ⁰ O for 95 hours. Then dissolve the Ganee in dilute acetic acid ₀

Under HÜhren then 600 ml of water with a temperature of 40 to - 45 ⁰ O added. It is then cooled, and the resulting product abgenutseht, washed with 1.3 1 of water and is dried at 60 ⁰ C. This gives 152 g (yield 63.5 β fi) S- (diethylaminoethyl) -2-meth03cy-4-amino-.5-nitrobenaamid (P. 206-208 ⁰ O) _a

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Level ^ O- .. J ^ fBiithylamino ^ ^

In a 2! 'Flask fitted with an ice stirrer, a thermometer and a dropping funnel, 152 g (0.49 Hol) of H-C diethylaininoethyl / S ^ metho ^ - ^ amino ^ S-nirrobenzamide, 230 ml of water optionally and 49 al concentrated Chlorwa3serstoffsäure, gives a thick checkout which 94 S tin be added is then rhitat at 50 ° 0 ©, whereupon 390 ml of hydrochloric acid portionwise eugösetet be "The reaction is strongly exothermic ,, The temperature reaches 80-100 ⁰ G ₀ If necessary, cooling is carried out.

When the addition is complete, the mixture is heated on the water bath until all of the tin has dissolved, _etc.

In a 3 1-Xolben provided a funnel with a stirrer, a Chermometer and a drip! "Are introduced 915 ml of sodium hydroxide, followed allmahlioh the above beaohriebene solution below 4O ⁰ O becomes isugesetst" The base separates si oh as a brown Oil. After cooling, it is abdekontiert is extracted and the aqueous solution with methylene "chloride ₀ The organic solution is washed once with water and dried over potassium carbonate _β Kethylenohlorid ansohlieeaend is distilled off, wherein

209814/1774

the distillation is ended under vacuum «Han receives 137 g (Yield = 100%) N- (Dläthylaininoätli5rl) -2 «methoxy-4f5'-diilraino < benzamides

Stage _i D _n »N-fcOiffihylaa ^

In a 2-liter flask equipped with a stirrer triebt, oxnem Shermometer and 3) ropf it is provided, 116 g (0.284 mol) of "H = (diethylaminoethyl) -2-methoxy ~ 4 # 5-diaminobenearaiddichlorhydrat, 568 ml Water and 28 ml of concentrated hydrochloric acid are added, and the mixture is heated to 40-45 ° C. It is then cooled to 0 °, whereupon 20 g (0.284 mol) of sodium nitrite are added dropwise by means of a dropper !. quilted, whereupon the temperature is again 20 ⁰ G anstei "= gen left the resulting solution is treated with charcoal, filtered and but dryness evaporated the solid | residue is taken up in 400 ml of boiling ethanol ₀ the remaining sodium chloride / is filtered, "By cooling and concentrating the alcoholic solution, the N- (diethylaminoethyl) -2-methoxy-4,5-aziaidobenzamia carbohydrate crystallizes out. It is filtered off with suction and washed with alcohol. ₃ It ceases a white solid (P ₀ 189 ° -191 ° C., yield «77% ^).

Example 2 '

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* »Q β»

Level A corresponds to level _{0 described in Example 1}

Stage B - ^ " , (I ^ & thyjl« ^^
5- »nitroben zam i d

14Q g (0.52 mol) of methyl 2-methoxy-4 ™ acet-P amino-5-nitrobenzoate, 500 ml of glycol and 201 g (0 , 52 Hol χ 3) l-> £ ethyl-2 «aminomethylpyrrolidine given» A yellow thick suspension is obtained, which is ^{heated to 55 0} C and is kept at this temperature for a period of 120 hours ₀ There is no conversion of the initial Precipitation feat «, rather it shows that after the end of the reaction a sample is completely soluble in dilute acetic acid,

Ansohliessend is cooled to 40 ° 0, after which 500 ml of water are added with stirring _e Each cooling to 2O ⁰ G is filtered with suction, the product obtained, washed with 1 1 water at 50 ⁰ O-dried to give 134 g (yield * 80? S) N- (1 ~

188 - 190 ° σ)

Level 0 ~ IT ^ Q ^ Ethyl ^^ pyr ro lidylme ^ diamine o

benzamide

Into a 2! »Flask with a stirrer, a thermometer

■ 2098 U / 1774

and a dropping funnel is provided, 120 g (0.372 mol) of N-C1 «iitnyl« 2 »pyrrolidylmethyl)« 2 = methoxy-4'-aitiAno-'5 ^ra niLtrGbensajrdd _f 170 ml of water and 37 ml of concentrated hydrochloric acid are added followed by heating at 50 ⁰ g · the hydrochloride formed lot completely soluble _o Then, 71 g of tin conces- ßetzt what SiOH the addition of 290 ml of concentrated öhlor «= · hydrogen acid ansonliesst, you let reaction! slightly exothermic. ~ The temperature reaches 65 ⁹ G. Naoh When the addition is completed, a thick precipitate forms. Then the mixture is heated on the water bath until all of the tin has dissolved.

In a second! Flasks of 1st equipped with a stirrer and a thermometer, 680 ml of sodium hydroxide are added, followed without 40 ⁰ C to. exceed the slurry described above to "'is .gesetzt ,, The base is deposited in the form of a brown oil from which the precipitation takes place also by some Zinnealeen c to dissolve the base 200 ml Hethylenohlorid' added, followed by the mineral salts are filtered off »

The organisohe solution is decanted off, is extracted and the aqueous solution once with 200 ml of methylene chloride and once with 100 ml of water ₀

The organic solution is washed once with 100 ml of water and dried over potassium carbonate. The ethylene chloride is

2098U / 1774

- ίο -

finally distilled, the distillation being terminated under vacuum. 10O g (yield "93%) of Sf- (1-ethyl-2-pyrrolidylmethyl) -2-metho: 5cy ~ 4 _? S-diarainobansaiaid ₀

Stage 3) * ff- (i ~ Athy X ~ 2 _n ~ pyrro ^
benzami d

112 g (0.278 Hol) H- (1-ethyl-2-pyrrolidylmethyl) -2-methoate-4 "5-diaminobenzaxnide are placed in a 2" flask equipped with a stirrer, a thermometer and a dropping funnel "· dlchlorhydrat, 580 ml of water and 28 ml konzentriertg hydrochloric acid given The whole is 40 ·» heated 45 ° g to a full resolution to ersielen "Subsequently ⁰ C is cooled to O, Bann are added dropwise 19 g (0.278 mol) Natriumuitr .il, dissolved in 28 ml of water, by means of the 'üropftrichters added ο stirring is set at O ⁹ C Amor- t for 1 hour, \ tforauf the temperature to 2O ° C is allowed to rise. Mused is evaporated to dryness, whereupon the solid residue is taken up in 400 ml of absolute alcohol _o The sodium chloride formed is filtered off in the heat, "The Aiko" holisohe solution is concentrated to give the N- (1-ethyl-2-pyrrolidylmethyl) -2-methoxy-4,5-azimidobenzamide crystallized out, dried off, washed with water and then washed with ether. 55 g (yield 85%) of the product were obtained in the form of white crystals (F ₀ 197 * 200 ^e G),

2 0 9BU / 177.4

~ 11 · - ■ ._ ■. ■■

rechtaarehena

Stage A is similar to the corresponding one described in Example 1 Step,

Level B ° H ^ (1, p

S-nitrobengamide. clockwise

80 g (0.3 mol) of meth (2.2 χ 0 _s 3 mol) right-handed t-ltliyl-ß ^ aiainomethylpyrrolidin given /

A yellow suspension heated to 55 ⁰ C * _s is This temperature is for a period τοη 216 hours * maintained

Then id, RAE 40 ⁰ G cooled, followed by 500 ml of water suction-filtered ₀ product obtained after cooling to 20 ⁰ C v / ith dao augesotst under HUhren, washed with water and dried at 11 ° §0 G "One arhält 45 g (Yield "58? 6} K- (1" ethyl "2-pyrrolidylmethyl}" 2- * methoxy - 4 "amino-'5- ^> nitrobenamide (dextrorotatory} '(F ₀ 185-187 * 0).

2 0 98 1 Λ / 177A

C -

c right dreaenfl

Reduction of 150g (0> 4 mol) of the right-handed Cblo2> -

• 5-ni - ', rö ^ siiiseÄl-i takes place in an autoclave with alcohol in one

95 ⁰ O as much in the presence of Saney-Nickel as the action lasts 1 hour. Per water to ffdruok beginning 64 "kg l> with a tea temperature of 45 * 0 _b

the reaction reaches the temperature 85 * 0, Bann fias-Hickel is filtered off in the warmth, whereupon the dichloro is sater use of 40 ml conaentated Ohlorwaeeer-

is produced, üaoh an IMcrystallization from -arMlt 110 g of the rotating dichlorohydrata of

β fO ^, f. 215 ^# C).

Jifaiwwtni'iiiiiaii Μ aaMaMUJhwJHJiiii "wiiiiw '* Hffllln itMifltitii iiBiiι. WFiwwmrra ^ ΎΛ mmmjaSKaaMäSSmm

. rotating

In a 1 1-Koll) "n equipped with a stirrer, a thermometer and a pot funnel, 43 g (O ₉ 107 Hol) of the rotating bichlorohydrate of Ji- (1-Xthyl ~ 2-pyrrolidyl-

BATH ORIGINAL

2098U / 1774

215.'ml tJass © 2? "sat -11 concentrated" GhlorvaseeretoffeSure given ^ Pas © sas © is saf 55. ⁰ O sur dissolution heated-whereupon 0®ö abgoMIblt _o S @ m & \ ferd @ n drop by drop by means of the Ssopftrioliters?, 5 g

C ©, 1:07 mol) of sodium nitrite, dissolved in 10 ml of water _s §imgas © tst _a Eühren for 1 hour at Q «ö continued whereupon DIE

iuaperatur der Misehung it will rise again to WiBgebisagsteape ^ atiis ¹ !

Me alcoholic I »8ßu & g wird-'konad & trlevt · Sas g © Mld @ t © aaidchlorhydrat crystallized from« It becomes a "bg © 2im ^ a © at imfi; with water and aaasohliaßsenä with Ither g @ waschea _o üan © rfcüt 23 g ( Austeute » 65 $} de® reohtsäseaendeii 0blorli ^ 3? At8 I ^ i ~ Ithyl-2 ^ pyrr © lid ^ lm © t ^
(I ⁵ »170 - 172 · 0),

Turning Linka

NaOH procedure in Example; 3 toesclirieheRon .Working method »d however äae right-to-open Asiin through the linto-rotating ©

is replaced * This gives the levorotatory Biohlorhydrat of Ή- (1 -Ithyl-2-pyrrolidylmethyl} "2" metho3C2r-4,5-aziBido · fconsaaiid, besitst the following characteristic Eigenecshaftem:

BATH ORIGINAL

2098 U / 1774 " ^: - ^: -

170 - 172 ° C) »- 5 ° (aqueous 5% solution)

Example 5 N-C ethyl propylaminoethyl) -2-methoxy-4,5-azimidobenzamide

Pie level A is the same as in example

Stage B - Ν - (& thyl-propylaOTinoethyl) -2-methoxy nitrobenzamide

In a 2! Flask provided with a stirrer and a thermometer, 188 g (0.7 mol) of methyl ~ 2-methoxy-4-acetsmino 5 ~ nitrobenzoate and 700 ml of glycol added _β Sann 273 g of (3 x 0.7 Hol) ethyl propyl ethylenediamine added

The resulting suspension is heated to 55 ^C C and held at this temperature during a breakdown tents 72 hours

The ester partially dissolves at the beginning of the reaction, whereupon the benzamide formed begins to precipitate Reaction, the whole thing is soluble in dilute acetic acid

Then 700 ml of water at a temperature of 50 ° 0 are added. After cooling, it is suction filtered, whereupon the obtained

2098U / 1774

. . ■■ .. '■ 17QKi 1 Γ

· * 15 ~

Profitakt washed and "dried at 50 ^ 0, Man exbg ϊ? 7 β (yield β 78.5 # 5 H- (l

{P. 195 ° 6)

Level 0 ~ lfc ( j ffli3KiB% @ Ef% ^

a-2 l «Xo3.1) ea _s read? ait eia «® Stffhrea?» aiaea

-So ial water «ad. 50 al lEoazönttieste CSnöBiasssjeeteffeite?

94 g ^ i ^ i eye-setstö -SSan βτϊύΛζ * m £ 55®% wsä gifet .330 fconzeatseierie 0iilo3eweasej? EtoifSl ¹ ^ e ia Üelsaen fojet & oiien

3) 1 © EeaMioa ist sta ^ k 9 ^ atli® »a _# W

In a 3 1-Kolbea, who with an iron sÜhrer "" inem Sh-iaaouna ^ te? a fropftriofrtar is beholding, vestäieg ». .915 flCL Ifatrii ^, given, before allffiihlioh the imrstehead * ä> e8cnr £ 6 ° "bsxie solution is sugeeetst without that an Xtiäpera ^? / Of 40 ° 0 is exceeded 3) is base spbsidet eioli in pure paste from, the again la 150 al Meth ^ lenGhlozld on ge «^ ird ₀ The aqueous solution -w is ex- with HethyleaoKLorid-

2098 H / 177

traced. The organic solution obtained is washed with water and dried over potassium carbonate. The methylene chloride is then distilled, whereupon the distillation is terminated under vacuum. 131 g (yield κ 90 $>) N- (ethylpropylamino & thyl) «* 2-» iaethoxy-'4,5-diaiiilnoT? Enzaiaid _{or the like are obtained}

Stage, D - K- (Ethylpropylamlnoäthyl) - "2 ~ meth03cy" 4 "$ -

on I d

In a 2! Flask equipped with a stirrer, a thermometer and a dropping funnel, 106 g (0.258 Hol)! »« - (Ethylpropylaminoethyl) -2 «methoxy ~ 4,5-aminobenzamide dichlorohydrate, 516 ml of water and 26 ml of concentrated hydrochloric acid are added. Then it is heated to dissolve the mixture. The mixture is cooled anechlieeeend to ^{0 °} C, and fttgt dropwise by means of the Irbpftrichtere 18 g (0.258 mol) of sodium "nitrite" dissolved in 20 ml water, _e After the addition is complete the mixture Elthron on a Semperatur of 0 ° 0 during a time Penne held for 1 hour, after which the granite is allowed to warm to ambient temperature »

The solution is treated anechliessend with charcoal, filtered and evaporated to dryness ₀ The solid residue is taken up in 300 al of boiling ethanol. In heat represents the remaining sodium chloride is filtered off ₀ After a Abktth-

2098U / 1774

¹⁷⁹⁵¹

lung as well as, 'a Konsentriez-ung the alcoholic LSsmg ϊα? & · - installs the 2Τ- (1ΐ · 1ΐ7ΐρΓορ ^ ΐΗΜηο &Η; 1 ^ 1} · -2 «- · ΐηβ ^ ο ^« 4? 5- · & 2ΐΕώά "benaamid aua _e It is siphoned off and washed with water »It is a soft solid (Γ. 155 ° ö)

Bapiel _ι 6 ·

ff-j []) iät ^^^

33 g (0.113 mol + 20%) of N- (I> iäthylaininoäthyl) -2 "metlioxy-4> 5-azimidobenzaiBid, dissolved in 66 ml of Ilethyj alcohol and 19 g (0.113 mol + 20%) of methyl iodide, are dissolved in a 250 ffil flask added 38 ml of methyl alcohol ₉ is then verniiso3it _p and the flask for 136 hours in a well-sealed state is allowed to stand "the product crystallizes out" spell is filtered with suction and dried "! times a Umkristalllsation from acetone, sohliasslich K- (2) iäthylaminoäth7l) -> 2-metho3Qr-4f5-azimidobenaainidjodmethylat (P, 205 ⁰ C) ₀ "

The compounds of the invention have been used in a number of Subjected pharmacological and clinical tests to determine, on the one hand, their high toxicity and, on the other hand, their anti-emetic properties To determine effectiveness «.

The acute ioxiaities that were determined by iföusen »

■■■ ". '■■■■ BAD ORIGINAL

209814/1774

show that the compounds according to the invention have such socialities have »which allow a therapeutic Vevwe & ötspg« The loaities are exemplified in the following table Form summarized:

links

per os

, in mg / kg of the compound

in the base state

intravenous intra «=» sub- • peritoneal ku-tan

H- (diethylaminoethyl) -2- 1500 143-146

(30 # Mormotho2y »4t 5-a8imidobenisajaid tali tat)

N- (1-Xthyl-2-pyrrolidylmethyl) -2-methO2ey-4 _s 5-azistldobenzamide

1517

methyl) -2-methoacy-4> 5-aisioüdobenzamidy rotating

yes- (1 -ethyl «2-pyrrolidyl-» iEethyl'.i "" 2 — methosy · —415 — azimi— dobenäainid »counterclockwise

84-85

83-84

387-400 600-576

214-216 330-321

248

207

339

243

The antieaetiscae effect of these compounds on the centers of refraction is using dogs using apomorphine according to the method of Chen und Sie or, edited by Duorot and F. Decourt, determined ο Groups of 4 dogs are used

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BATH ORIGINAL

Bas apomorphine is administered subcutaneously at a dose of 0.1 mg / kg administered. The compounds to be tested are also administered subcutaneously 30 minutes beforehand. Vomiting occurs 30 minutes after the injection of appmorphine counted,

The values below have been obtained using some of the compounds according to the invention achieved s

links

N- (diethylaminoethyl) ~ 2-methosy-4 » 5-azimidobenzamide

N- (1-ethyl-2- pyrrolidylaethyl) -2- -4,5-aziaidobenBamid

H- (1-Xthyl-2-pyrrolidylaethyl) -2-methoxy-4 »5- ^ng i ^ ^^ ^f > ^ ^{> aT> gfljn} i ^» rotatory

Nr (1-Xthyl-2-pyrrolidyliadthyl) «* 2-methoxy-4 , 5-a2imi dobensamid, linked rotating

Level of protection at a dose of 250 mt / kg (base)

100

100

$ 100>

$ 100>

The compounds according to the invention have the interesting ones pharmacological property that they are not cataleptic TQr swei invention ^ exnäsee connections goes the cataleptieohe Effectiveness is evident from the results below, with the

2098 U / 177

Results are measured at the level of the effect, i.e. after 30 - 360 meows.

Connections way

methoxy-4,5-azimidobeii2iainId subcutaneous effect of

20 # at

H- (diethylaminoä1; hyl) -2- N- (1-ethyl-2-pyrrolidylmethyl) -

2-methoxy-4,5-asimidobenzamide subcutaneous * 84.8

The experimental results were confirmed in the clinic, where the products according to the invention are in the form of tablets or Ampoules were administered as pharmaceutically acceptable salts

The treatments did not give rise to clinical conditions corresponding to the phaxma dynamics. In addition, they are compounds according to the invention contractually · the broadening stop quickly and do not recur after treatment is stopped. To a 70-year-old can who suffered from severe gastrointestinal disease with repeated vomiting during food intake, were given 2 ampoules administered per sag, which contain 10 mg of ÜT- (I "iäthylGminoatnyl) -2-methox; f-4,5-aBimidobenBaaidohlorhydrat", The tolerance was

2098U / 1774

excellent, where it was found «that within 2 Say a noticeable reduction in broadening occurred, it was possible to re-feed the patient » The congestion ceased after 4 days of treatment. constantly onο

In a woman aged 55 years who suffered from breast cancer and was ^{treated with chloroethasines (moutardee ä I 9} azote) (|, the hereditary lesions heard after the administration of 3 ampoules with 10 mg K- (i-ethyl -2-pyrrolidylmethyl) -2-methoxy-4,5-a2imidobenaamido carbohydrate per day to ₀

The antiemetic compounds according to the invention can be administered in the form of pharmaceutically acceptable salts, tablets or injectable ampoules. In addition, administration in the form of aerosols, suppositories, granulated sugars, syrups with ingredients or the like is possible _a

2098 U / 177 A

Claims (5)

Claims sas = »ar κ ==: =! a = s 1. 2-Alkoiy »4» 5-aziinidobeiizainide of the general formula C3ONH (OH ₂ ) _n - A OB wherein A is a mono »or dialkylamino radical of the formula -N, where the substituents R ₁ and R ₂ * are the same or can be different, hydrogen or alkyl radicals with 1-5 carbon atoms and with the formation of a ring with or without nitrogen) oxygen or sulfur can be connected »where, if the ring contains a nitrogen atom» this can be substituted by an alkyl group with 1-5 carbon atoms »or a heterocyclic Best of the formula B. 2098U / 1774 where · ■. R is an alkyl radical with 1 - 5 carbon atoms, iet, ta represents an integer below 4, B is an alkyl or alkenyl radical with 1 - 5 carbon atoms symbolized and η is 1 or 2 » as well as their clockwise and counterclockwise "forms, whose pharmaceutical» Zeutisoh compatible acid addition salts with kineral acids or organic acids and their pharmaceutically acceptable quaternary ammonium ales. 2. ii- (diethylaminolithyl) -2-mathoxy-4,5-asimidoben2ainiö _c 3. K- (1-Xthyl-2-pyrrolidyltoethyl) -2-metho3y »4 _f S-asimidobenzaiaid, 4 · Eeohtsdrehendee H- (i-Ethyl-2-pyrrolidylmethyl) -2Hiiethoxy-4t 5-ejBimidobenBaiiid. 5. Rotating F ~ (1-Xthyl-2-pyrrolidylmethyl) -2-ffletho ^ - * 4 » 6 · H- (1-ethyl-propylaminoethyl) -2-metho3iy-415-azjnidobenzamido methylate. 2098U / 1774 ~ 24 - Process for the preparation of 2-alkoxy-4,5- ^c: 'äi3iraia9bensaiiiiänen according to claim 1, characterized in that a substituted 2-alkoxy-4,5-aminebenzamide is treated with a metal nitrite in an acidic medium, whereupon the acid audition salts using a Mineral acid or an organic acid or the quaternary ammonium salts are produced ₀ 209 8 U / 1774