NO138250B - ANALOGICAL PROCEDURE FOR THE PREPARATION OF PHARMACOLOGICALLY ACTIVE BENZYLAMINES - Google Patents

Description

The present invention relates to an analogous process for the production of pharmacologically active benzylamines with the general formula I:

where

R^ is a hydrogen atom or a lower alkanoyl- or an optionally

with halogen substituted benzoyl group,

R 2 is a hydrogen, chlorine or bromine atom,

R is a fluorine atom; a methyl group in the 3-, 4- or 5-position,

or, when R^ means a lower alkanoyl or an optionally halogen-substituted benzoyl group or when R^ means a chlorine or bromine atom, also in the 2- or 6-position in the phenyl nucleus;

a linear or branched alkyl radical of 2-4 carbon atoms; a trifluoromethyl, cyano, carbamoyl, carbalkoxy, acetyl or 1-hydroxyethyl group; a carboxyl group when at least one of the radicals R 1 , R 2 , R 4 or R 1 does not mean a hydrogen atom; a lower alkoxy group in the 3-, 4- or 5-position, or, when R 2 means a chlorine or bromine atom, also in the 2- or 6-position of the phenyl nucleus; or an aminomethyl group of the formula:

where R6 and R7, which may be the same or different, mean lower alkyl, cycloalkyl or hydroxycycloalkyl groups with 5-7 carbon atoms or together with the nitrogen atom form a

pyrrolidine, piperidine or morpholine ring,

R^ and R^, which may be the same or different, are hydrogen atoms,

linear or branched alkyl radicals with 1 to 5 carbon atoms which may be substituted with 1 or 2 hydroxy groups, alkenyl radicals with 2 to 4 carbon atoms, cycloalkyl radicals with 5 to 7 carbon atoms which are optionally substituted with one or

two hydroxy groups, benzyl, morpholinocarbonylmethyl groups or together with the nitrogen atom a pyrrolidine, piperidine, hexamethyleneamine, morpholine, N-methylpiperazine or

camphidin ring,

and their physiologically compatible acid addition salts with inorganic or organic acids.

The compounds of the above general formula I exhibit valuable pharmacological properties, in particular an anti-ulcer effect, a secretolytic, antitussive and a stimulating effect on the production of surfactant or the anti-atelectase factor in the alveoli.

The procedure for producing the new compounds is distinctive in that:

a) A compound of the general formula II:

where and is as stated above,

R3' is the residue -CH2_X or has the meanings given for R3 at the beginning, and

X means a chlorine, bromine or iodine atom, a hydroxyl group, an acyloxy, sulfonyloxy, alkoxy, aryloxy or aralkyl radical, a trialkylammonium group or a pyridinium radical,

is reacted with an amine of the general formula III

where R 4 and R 4 are as indicated at the outset.

In the above-mentioned formula II, the meanings of chlorine or bromine, hydroxy, acetyloxy, butyryloxy, benzoyloxy, methylsulfonyloxy, p-toluenesulfonyloxy, methoxy, ethoxy, phenoxy, trimethylammonium or pyridinium residue.

X can thus mean any leaving group, which makes it possible to intermediately form a benzyl cation starting from a compound with the above general formula II.

The reaction is suitably carried out in a suitable solvent such as e.g. carbon tetrachloride, chloroform, methanol, tetrahydrofuran, benzene, toluene, ether, dioxane, tetralin or in an excess of the amine used with the general formula III, and depending on the reactivity of the sestene X at temperatures between -70 and 200°C. However, the turnover can also be carried out without solvent.

A compound with the general formula II is reacted where

X means a hydroxyl group and where an acylamino group is in the 2-position, the acyl group can be split off during the reaction.

If X is a sulphonyloxy acid residue such as, for example, the 4-methylphenyl-sulphonyloxy group, the reaction is preferably carried out at temperatures between -70 and 50°C in a solvent such as, for example, an aliphatic or cyclic ether.

If X is a halogen atom, the reaction is preferably carried out at temperatures between 0 and 150°C, e.g. at the boiling temperature of the solvent used, and suitably in the presence of a halogen hydrogen binding agent, e.g. an inorganic base such as sodium carbonate or sodium hydroxide, an ion exchanger, a tertiary organic base such as triethylamine, pyridine or in an excess of the amine used with the general formula III. Hereby, a tertiary organic base used can also simultaneously serve as a solvent.

If X represents an acyloxy acid residue such as an acetoxy or a benzoyloxy residue or an alkoxy, aryloxy or aralkyl residue, then the reaction is possibly carried out in the presence of an acidic catalyst such as e.g. ammonium chloride, acidic aluminum oxide or sulfuric acid, and preferably at temperatures between 0 and 200°C.

If X is a hydroxy group, the reaction is possibly carried out in the presence of an acidic catalyst such as e.g. sulfuric acid, hydrobromic acid, p-toluene acid, a lower carboxylic acid such as e.g. propionic acid or butyric acid or optionally in the presence of an alkaline catalyst such as e.g. potassium hydroxide, magnesium oxide or sodium amide, preferably at temperatures between 120 and 180°C. However, the turnover can also be carried out without solvent.

If X is a trialkylammonium or pyridinium group, the reaction is preferably carried out in an excess of the amine used with the general formula III as solvent at temperatures between 120 and 180°C. However, the turnover can also be carried out without solvent.

b) For the preparation of compounds of the general formula I where R2 means a chlorine or bromine atom, and R^ and/or R^

is as indicated at the outset with the exception of an alkenyl residue, a compound with the general formula IV is halogenated:

where R^ and R^ are as indicated at the outset, and

R^' and R,.' have the meanings given for R4 and R5 at the beginning with the exception of the alkenyl residue.

The reaction is carried out with a halogenating agent, e.g. with chlorine, bromine, tribromophenol bromine or phenyliododichloride, preferably in a solvent, e.g. in 50 to 100% acetic acid or in methylene chloride resp. tetrahydrofuran in the presence of a tertiary organic base such as e.g. triethylamine or pyridine, and suitably at temperatures between -20 and 50°C. Per mole of a compound with the general formula IV, which can be used as a base or also as a salt, e.g. as mono-, di- or trihydrochloride, 1 mol of halogenating agent or a small excess thereof is suitably used. If a halohydrogen acid salt is formed during the reaction, this can be isolated as such or purified further over the base if desired.

c) For the preparation of compounds with the general formula I where R^ and/or R^ represents a hydrogen atom, a

or two protecting residues from a compound of the general formula V:

where R 2 , R 1 and R 2 are as indicated at the outset,

means a hydrolytically or hydrogenolytically cleavable protective residue for an amino group or has the meanings given for R1 at the beginning and

Y2 means a hydrolytically or hydrogenolytically cleavable protective residue for an amino group or have they for R^introductory

show indicated meanings, with at least one of the residues Y1 and Y2 meaning a protective residue.

Does Y1 and/or Y2 represent, for example, an arbitrary acyl residue,

e.g. an acetyl, benzoyl or p-toluenesulfonyl residue, a trimethylsilyl or tetrahydropyranyl-(2) residue, the cleavage of these residues is carried out hydrolytically in the presence of a solvent; e.g.

using ethanolic hydrochloric acid or aqueous-alcoholic caustic soda,

suitably at temperatures between 20 and 150°C, however preferably at the boiling temperature of the solvent used. Herein, in a compound with the general formula V R3 means a cyano, carbalkoxy or carbamoyl group, then these can simultaneously be saponified into a carboxyl group.

If Y1 and/or Y^, for example, means a benzyloxy-carbonyl or benzyl residue, the cleavage of these residues is carried out hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as e.g. palladium, preferably in a solvent such as methanol, methanol/water or methanol/hydrochloric acid and preferably at room temperature. In the turnover, they can by the definition of the residues R. and/or Rj. said alkenyl residues are simultaneously transferred to the corresponding alkyl residues and the acetyl and cyano groups mentioned in the definition of the residue R^ are simultaneously reduced.

d) For the preparation of compounds of the general formula I where R^ denotes a 1-hydroxyethyl group, a compound of the general formula VI is reduced:

where R 1 , R 4 or 3 R 5 are as indicated at the outset.

The reduction is preferably carried out in a solvent such as e.g. methanol, methanol/water, ethanol, isopropanol, ether, tetrahydrofuran or dioxane, suitably with a complex metal hydride, e.g. lithium aluminum hydride or particularly advantageously with sodium borohydride, with an aluminum alcoholate such as e.g. aluminum isopropylate in the presence of a primary or secondary alcohol, such as ethanol or isopropanol or with hydrogen in the presence of a catalyst such as e.g. Raney nickel, platinum or palladium/charcoal, suitable at temperatures between -20°C and the boiling temperature of the solvent used.

If the reduction is carried out with catalytically activated hydrogen, the alkenyl residues mentioned in the definition of the residues R 4 and/or R 1 can be transferred into the corresponding alkyl residues and/or the benzyl residues mentioned can be split off hydrogenolytically.

e) For making connections with the general

formula I where R_ means a carboxyl group, a compound is hydrolyzed

with the general formula (VII):

where R^, R^, R^ and R^, are as indicated at the outset and A means a functional derivative of a carboxyl group.

For the functional derivatives mentioned in the definition of the residue A, in particular amides, iminoesters, esters or nitriles come into consideration.

The reaction is suitably carried out in a solvent such as e.g. methanol, ethanol, methanol/water, ethanol/water, dioxane/water or water in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid or in the presence of a base such as e.g. sodium hydroxide and at temperatures between 50 and 150°C, however preferably at the boiling temperature of the solvent used. During the reaction, however, the residue R^ can also be cleaved off at the same time, if this is an acyl residue.

f) For the preparation of compounds of the general formula I where R^ means a hydrogen atom, R^ is as at the beginning

indicated with the exception of a cyano, carboxyl, carbaloxy, carbamoyl or acetyl group and R^ and/or R,, does not mean a morpholinocarbonylmethyl residue, a compound of the general formula VIII is reduced:

where R2 and R4 and R1, with the exception of a morpholinocarbonylmethyl residue and R^ with the exception of a cyano, carboxyl, carbamoyl, carbalkoxy and acetyl group are as indicated at the outset.

The reduction is conveniently carried out in a solvent with nascent hydrogen, e.g. with sodium in ethanol, with catalytically activated hydrogen or with complex metal hydrides, e.g. with sodium borohydride in pyridine or particularly advantageously with lithium aluminum hydride in ether or tetrahydrofuran, preferably at slightly elevated temperatures, e.g. at temperatures between 30 and 70°C, or at boiling temperatures for the solvent used.

g) A compound of the general formula IX:

where R2 to Rj. is, as stated at the outset, reduced.

The reduction is suitably carried out in a solvent such as e.g. water, methanol, ethanol, water/methanol or ethyl acetate, preferably with nascent hydrogen, e.g. zinc/glacial acetic acid or ferric/hydrochloric acid, with hydrogen in the presence of a catalyst such as e.g. Raney nickel, platinum or palladium/coal, with a complex metal hydride such as lithium aluminum hydride or with stannous chloride/hydrochloric acid, suitably at temperatures between 0 and 100°C.

For the preparation of a compound of the general formula I, where R 3 means an acetyl group and/or R 4 and/or R 5 means alkenyl residues, the reaction is preferably carried out with stannous chloride/hydrochloric acid.

If the reduction is carried out with catalytically activated hydrogen in the presence of a corresponding carboxylic acid anhydride, compounds of the general formula I are obtained, where R 2 - means a corresponding acyl group.

h) For the preparation of compounds of the general formula I where R,, does not mean a residue which is substituted by an or

several hydroxy groups and R4 and/or R5 do not mean hydrogen,

a compound of the general formula X: where R^, R^, R^ and R^ are as indicated at the outset, is alkylated with a compound of the general formula XI:

where R^" have the meanings given at the beginning for R, with the exception of hydrogen and the residues which are substituted with one or two hydroxyl groups and

W means a halogen atom or a sulfonic acid residue.

The reaction is suitably carried out in a solvent such as e.g. methanol, dioxane or dimethylformamide and suitably at temperatures between -20 and 150°C, however preferably at the boiling temperature of the solvent used. Methylation can also be carried out with formaldehyde in the presence of formic acid at an elevated temperature, e.g. at the boiling temperature of the reaction mixture.

i) For the preparation of compounds of the general formula I where R does not mean an acyl group, an aldehyde of the general formula XII is reacted:

where R^ and R^ are as indicated at the outset and

R3" has the meanings given for R3 at the beginning with the exception of an acetyl group, with an amine of the general formula III:

where R4 and R^ are as stated at the beginning, resp. with the corresponding formamide in the presence of formic acid.

The reductive amination is preferably carried out at temperatures between 50 and 250°C, optionally in a solvent and optionally during simultaneous distillation of the water formed. However, it is particularly advantageous when, during the reaction, the amine with the general formula III and/or formic acid simultaneously serves as a solvent. If and/or R,, in a compound of the general formula III means a hydrogen atom, the resulting reaction mixture is heated after the reaction with a dilute acid such as e.g. 2n hydrochloric acid under reflux.

j) For the preparation of -compounds with the general formula I where R^ means a hydrogen atom and R^ is as indicated initially with the exception of an acetyl group, a compound with the general formula XIII is reduced:

or a compound of the general formula Xlla:

where R^, R2 and R,, are as indicated at the outset,

R " has the meanings given for R at the beginning with the exception of an acetyl group and

Z means a cyclohexylidene residue which is optionally substituted with one or two hydroxy groups, an alkylidene residue with 3 to 5 carbon atoms or a morpholinocarbonylmethylidene residue.

The reduction conveniently takes place with catalytically activated hydrogen, e.g. with hydrogen in the presence of Raney nickel or Raney cobalt, with nascent hydrogen, e.g. with activated metallic aluminum and water, with sodium amalgam and ethanol, with zinc and hydrochloric acid or particularly advantageously with a complex metal hydride such as e.g. sodium borohydride in a suitable solvent such as e.g. methanol, ethanol, ethanol/water, tetrahydrofuran, dioxane, dioxane/water, pyridine or ether and at temperatures up to the boiling point of the solvent used, for example at temperatures between -50 and 100°C.

A compound of the general formula XIII or XHIa can also be reduced directly in situ without prior isolation.

k) For the preparation of compounds of the general formula I where R does not mean a 1-hydroxyethyl group, a compound of the general formula XIV is reacted:

where R^ and R^ are as indicated at the outset and

R^"' has the meanings indicated for R^ at the beginning with the exception of a hydroxyethyl group, with an amide of the general formula XV:

where R4"* means a hydrogen atom or an alkyl radical with 1 to 3 carbon atoms and

R 5"' means an alkyl radical with 1 to 3 carbon atoms or a cyclohexyl group or

R4"' and R^"' together with the nitrogen atom mean a morpholino or piperidinore residue, or with an amide of the general formula XVa:

where Rj and R,, are as indicated at the beginning and

Rg means an alkyl, aryl or aralkyl radical.

The reaction is suitably carried out in a solvent such as e.g. tetralin and at temperatures between 100 and 250°C, however preferably at temperatures between 120 and 180°C. However, the turnover can also be carried out without solvent.

1) A compound of the general formula XVI:

where R 2 and R 3 are as indicated at the outset and

Rg is a hydrogen atom, an alkyl, aryl, aralkyl or hydroxy group,

is reacted with an amine of the general formula III:

where R4 and Rj. is as indicated at the outset, and optionally the resulting reaction product is then hydrolysed.

The reaction is suitably carried out in a solvent such as e.g. tetralin or in an excess of the amine used with the general formula III at temperatures between 100 and 200°C, however preferably at temperatures between 120 and 180°C. However, the turnover can also be carried out without solvent.

The optionally connected hydrolysis is preferably carried out in the presence of an acid such as e.g. hydrochloric acid or in the presence of a base such as caustic soda in a polar solvent such as water, ethanol/water or dioxane/water and at temperatures up to the boiling temperature of the solvent used.

For the groups mentioned in the definition of the radical R_ above, the meanings of the methyl, ethyl or phenyl radicals come into consideration in particular.

m) For the preparation of compounds of the general formula I where R^ denotes a carbolicoxy group, a compound of the general formula XVII is reacted:

where R^, R2/R^ and R^ are as indicated at the outset and B means a carboxyl group or a functional derivative thereof, with a compound of the general formula XVIII:

where R^O means a lower alkyl residue and

D means a hydroxyl group or a halogen atom.

The reaction is suitably carried out in a solvent such as e.g. ethanol, tetrahydrofuran, dioxane or in an excess of the compound used with the general formula XVIII, optionally in the presence of an alcoholate such as e.g. sodium ethylate or an acid such as ethanolic hydrochloric acid at temperatures between 0 and 100°C, preferably at the boiling temperature of the solvent used. An optionally connected hydrolysis of the intermediately formed iminoester is carried out with water and an optionally connected entacylation is preferably carried out with the corresponding alcohol and an acid.

For the functional derivatives mentioned in the definition of the residue B, in particular anhydrides, acid halides, amides, amidines, esters or nitriles come into consideration.

If a compound of the general formula I is obtained by the methods a) to m), where R3 means a cyano group, this can be transferred to the corresponding carbamoyl compound of the general formula I by means of partial hydrolysis, e.g. with aqueous-alcoholic caustic soda, and/or a compound with the general formula I where R± denotes a hydrogen atom and 1^, R3, R4 and R5 are as initially indicated with the exception of a residue containing a reactive hydrogen atom, these can, if desired acylated afterwards. This conversion is conveniently carried out with a reactive acid derivative such as e.g. an acid halide, acid anhydride or mixed acid anhydride or in the presence of a water-extracting agent such as e.g. N,N'-dicyclohexyl carbodiimide.

The obtained compounds of the general formula I can, if desired, be transferred, in their^. physiologically compatible acid addition salts with one, two or three equivalents of the acid in question. As acids, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, maleic acid or fumaric acid have proven suitable.

The compounds of the general formula II used as starting materials can be prepared according to usual methods, e.g. by reacting the corresponding toluene derivatives with N-bromosuccinimide resp. with halogen under UV irradiation, from the corresponding benzyl alcohols with thionyl chloride or by reacting a corresponding benzyl halide with an alkali salt of a carboxylic acid,

with an alkali alcoholate or phenolate or by halogenation of a corresponding benzylammonium salt.

The benzylamines with the general formulas IV, V, VI, VII are obtained by reacting the corresponding benzyl halides with the corresponding amines.

The benzamides of the general formula VIII are obtained, for example, from the corresponding isatoic anhydrides by reaction with the corresponding amines.

Compounds with the general formulas II, IX, X and XVII used as starting materials are obtained, for example, by reacting a corresponding benzyl halide with a corresponding amine or a starting compound with the general formula X is also obtained by reacting a corresponding 4H-3,1-benzoxazine with a corresponding amine.

An aldehyde with the general formula XII used as starting material is obtained, for example, by oxidation of a corresponding benzyl alcohol, suitably with manganese dioxide or by hydrolysis of a corresponding nitrone.

Compounds with the general formulas XIII and XHIa used as starting materials are obtained, for example, by reacting a corresponding carbonyl compound with a corresponding amine.

Compounds of the general formulas II and XIV used as starting materials are obtained, for example, by reduction of a corresponding aldehyde or by saponification of a corresponding benzyl halide.

A compound with formula XVI is obtained, for example, by halogenation of a corresponding benzoxazine derivative or by splitting off water from a 2-acylamino-benzyl alcohol.

As mentioned at the outset, the new compounds of the general formula I have valuable pharmacological properties, in particular an anti-ulcer effect, a secretolytic, antitussive effect and a stimulating effect on the production of surfactant or the anti-atelectase factor from the alveoli.

For example, the following compounds were examined for their biological effects: A = 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine hydrochloride,

B = N-ethyl-2-amino-3-bromo-5-carboxy-N-cyclohexyl-benzylamine hydrochloride,

C = N-ethyl-2-amino-5-bromo-H-cyclohexyl-3-fluoro-benzylamine hydrochloride,

D = N-(2-amino-5-bromo-3-methyl-benzyl)-hexamethyleneamine dihydrochloride,

E = N-(2-amino-5-bromo-4-tert.butyl-benzyl)-morpholine dihydrochloride,

F = 5-acetyl-2-amino-3-bromo-N,N-dimethyl-benzylamine and

G = 2-amino-3-bromo-N,N-dimethyl-5-fluoro-benzylamine hydrochloride.

1. Secretolytic action:

Expectoration experiments were carried out on anesthetized guinea pigs or on anesthetized rabbits (see also Perry and Boyd, Pharmacol. exp. Therap. 13, 65 (1941)). The substances were applied to 6 to 8 animals in a dosage of 8 mg/kg p.o. The calculation of the increase in secretion (2-hour values) took place by comparing the amount of secretion before and after substance addition.

The circuit tests were carried out on 3 cats under chloralose-urethane anesthesia after intravenous administration of 2.4 and 8 mg/kg of the substance to be examined:

Experiments on guinea pigs:

Experiments on rabbits:

2. Anti-ulcer effect:

The effect of the test substances on wounds was determined according to the method of K. Takagi et al (Jap. J. Pharmac. 19_, 418 (1969)). In addition, the abdominal cavity of female rats with a body weight between 220

and 250 g were opened under general anesthesia and the stomach was left outside. Then 0.05 ml of a 5% acetic acid solution was injected in a place between the Muscularis mucosae and the submucosa. The abdominal cavity was closed again after the injection. The abscess that appeared after 3 to 5 days at the application site in the mucous skin was treated for 3 weeks by mixing the test substance in dosages of 50 and 100 mg/kg to the feed (6 animals/dose). The control animals only received the powdered feed.

After three weeks of treatment, the animals were killed, the stomachs removed and the wounds determined by measuring the length and width of the abscess. The substance effect was calculated against the controls (100%): At a dosage of substance A of 50 mg/kg p.o. a reduction of the wound of 52% was found and at a dosage of 100 mg/kg p.o. a wound reduction of 79% compared to the controls.

3. Acute toxicity:

The acute toxicity of the test substances was roughly determined on groups of 5 white mice each after a single administration of 1000 or 2000 mg/kg p.os.:

The new compounds of the general formula I allow

for pharmaceutical applications incorporate into the usual pharmaceutical preparations such as e.g. tablets, dragées, capsules, suppositories, ampoules and solutions, possibly in combination with other active substances. The single dose thereby amounts to 1 to 100 mg, preferably 4 to 60 mg, and the daily dose 2-300 mg, preferably 4 to 200 mg. For compounds with secretolytic action, the single dose amounts to 1 to 20 mg, preferably 4 to 15 mg, and with antiulcer action 25 to 100 mg, preferably 30 to 60 mg.

The following examples shall explain the invention in more detail:

Example 1

2- amino- 3- bromo- N, N- dimethyl- 5- fluoro- benzylamine

Dissolve 5.5 g of 2-amino-3-bromo-5-fluoro-benzyl alcohol in 150 ml of chloroform. While stirring and cooling with ice, 7.13 g (4.35 ml) of thionyl chloride are added dropwise, whereby a yellow precipitate falls out. The suspension is allowed to stand overnight at room temperature and is then evaporated to dryness under vacuum at room temperature on a rotary evaporator. The crude benzyl chloride thus obtained is suspended in 100 ml of chloroform. While stirring and cooling with ice, 20 ml of dimethylamine is added, whereby a clear solution is obtained. The mixture is allowed to stand for 30 minutes with ice cooling and it is then extracted twice with saturated potassium carbonate solution. The chloroform phase is washed with water, dried over sodium sulphate and evaporated to dryness in vacuo. The rest in

taken up in absolute ethanol and acidified with ethereal hydrochloric acid to pH 3. The precipitated hydrochloride is suctioned off and dissolved in absolute ethanol. After adding activated charcoal, the solution is heated to boiling. After filtering off the activated carbon and adding ether, colorless crystals are obtained.

Melting point: 241-243°C.

Example 2

2- acetylamino- N, N- diethyl- 3- methyl- benzylamine

22 g of 2-acetylamino-3-methyl-benzyl bromide in 1.6 l of carbon tetrachloride are added to 20 g of diethylamine and boiled for 1 hour under reflux. The reaction solution is then evaporated, the residue is dissolved in 1 1 2n hydrochloric acid, shaken twice with chloroform, the acidic phase is made alkaline with concentrated ammonia and extracted three times with chloroform. The organic phase is evaporated and the residue is chromatographed over silica gel with acetone-methanol (9:1). The crude product obtained is dissolved in ethanol, acidified with ethanolic tartaric acid and 2-acetylamino-N,N-diethyl-3-methyl-benzylamine is crystallized as tartrate by adding ether.

Melting point: 134-136°C.

Example 3

2- acetylamino- 5- bromo- N, N- diethyl- 3- diethylaminomethyl- benzylamine

16.5 g of 2-acetylamino-5-bromo-3-bromomethyl-benzyl bromide i

1.6 1 carbon tetrachloride is added to 24 g of diethylamine and boiled for 1 hour under reflux. The reaction solution is then evaporated, the residue is dissolved in 0.7 1 2N hydrochloric acid, shaken out twice with chloroform, the hydrochloric acid phase is made alkaline with concentrated ammonia and extracted three times with chloroform. The organic phase is dried with sodium sulphate and the solvent is distilled off. The residue is separated by column chromatography over silica gel with ethyl acetate-methanol (1:1),

the corresponding fractions are combined, they are evaporated to dryness and by recrystallization from petroleum ether 2-acetylamino-5-bromo-N,N-diethyl-3-diethylaminomethyl-benzylamine is obtained.

Melting point: 91.5-93°C.

Example 4

2- acetylamino- 5- bromo- 4- tert. butyl-N-cyclohexyl-N-methyl-benzylamine

25 g of 2-acetylamino-5-bromo-4-tert.butyl-benzyl bromide i

1.5 1 of carbon tetrachloride is boiled with 23 g of N-methyl-cyclohexylamine i

1 hour under reflux, cool, the precipitated N-methyl-cyclohexylamine hydrobromide is filtered off and the filtrate is evaporated. The rest is added

2n hydrochloric acid and extracted twice with benzene. The acidic phase is made alkaline with concentrated ammonia, shaken three times with chloroform, the organic phase is dried and evaporated. The residue is purified by column chromatography over silica gel with ethyl acetate-chloroform (1:1) and 2-acetylamino-5-bromo-4-tert.butyl-N-cyclohexyl-N-methyl-benzylamine hydrochloride is precipitated from ethanol-ether with ethanolic hydrochloric acid. The crude product is recrystallized from ethanol-ether.

Melting point: 2 31-234°C.

Example 5

2- acetylamino- 4- tert. butyl-5-chloro-N-cyclohexyl-N-methyl-benzylamine

29 g of 2-acetylamino-4-tert.butyl-5-chloro-benzyl bromide i

1.5 1 of carbon tetrachloride is boiled with 26 g of N-methyl-cyclohexylamine i

2 hours under reflux, cool, N-methyl-cyclohexylamine hydrobromide is filtered off and the filtrate is evaporated. The residue is taken up in 2N acetic acid, shaken out with chloroform, the acidic phase made alkaline with concentrated ammonia, extracted three times with chloroform and the organic phase evaporated. After column chromatographic purification over silica gel with ethyl acetate-chloroform (1:1), 2-acetylamino-4-tert.butyl-5-chloro-N-cyclohexyl-N-methyl-benzylamine crystallizes from absolute ethanol and recrystallized from ethanol.

Melting point: 174-175.5°C.

Example 6

2- acetylamino- 5- tert. butyl-N-cyclohexyl-N-methyl-benzylamine

23 g of 2-acetylamino-5-tert.butyl-benzyl bromide in 1.6 l of carbon tetrachloride are boiled with 24 g of N-methyl-cyclohexylamine for 1 hour under reflux. After cooling, N-methyl-cyclohexylamine hydrobromide is filtered off, the filtrate is evaporated and the crude product is purified by column chromatography over silica gel with ethyl acetate. The corresponding fractions are evaporated and 2-acetylamino-5-tert.butyl-N-methyl-benzylamine is crystallized from petroleum ether.

Melting point: 111-112.5°C.

Example 7

4- acetylamino- 3- tert. butyl-N-cyclohexyl-N-methyl-benzylamine

56 g of 4-acetylamino-3-tert.butyl-benzyl bromide in 500 ml of chloroform are boiled with 48 g of N-methyl-cyclohexylamine for 1.5 hours at reflux, then shaken three times with water and the organic phase evaporated. The residue is purified by column chromatography over silica gel with chloroform-methanol (5:1) and 4-acetylamino-3-tert.butyl-N-cyclo-ihexyl-N-methyl-benzylamine is crystallized from absolute ethanol-ether with the addition of absolute ethanolic hydrochloric acid.

Melting point: 240-243°C (dec.).

Example 8

5- acetyl- 2- acetylamino- N/ N- dimethyl- benzylamine

21 g of 5-acetyl-2-acetylamino-benzyl bromide in 500 ml of chloroform is added to 8.1 g of dimethylamine and stirred for 30 minutes. With the onset of an exothermic reaction, the substance dissolves. The reaction solution is then shaken with water three times and with 2N hydrochloric acid twice. The hydrochloric acid phase is extracted with chloroform, made alkaline with 2N ammonia and shaken twice with chloroform. The organic phase is evaporated, the residue is purified column chromatographically over silica gel with ethyl acetate and the corresponding fractions are combined and evaporated to dryness whereby crystalline 5-acetyl-2-acetylamino-N,N-dimethylbenzylamine is obtained.

Melting point: 68-72°C.

Example 9

2- amino- 3- bromo- N- cyclohexyl- 5- fluoro- N- methyl- benzylamine

Dissolve 3 g of 2-amino-N-cyclohexyl-5-fluoro-N-methyl-benzylamine in 30 ml of glacial acetic acid. While stirring, a solution of 1.98 g (0.63 ml) of bromine in 20 ml of glacial acetic acid is added dropwise at room temperature. After the addition is finished, stir for a further 10 minutes and then add 10n sodium hydroxide solution under ice cooling until pH 9 is reached and shake the mixture twice with 150 ml of methylene chloride each time. The combined methylene chloride solutions are washed with water, dried over sodium sulfate and evaporated to dryness under vacuum. The residue is dissolved in absolute ethanol and acidified with ethanolic hydrochloric acid to pH 3. The precipitated hydrochloride is filtered off with suction and recrystallized from a mixture of absolute ethanol and ether.

Melting point: 222-224°C.

Example 10

2- amino- 3- bromo- 5- tert. butyl-N-cyclohexyl-N-methyl-benzylamine

10 g of 2-amino-5-tert.butyl-N-cyclohexyl-N-methyl-benzylamine are dissolved in 50 ml of 90% acetic acid and 5.8 g of bromine are added dropwise while stirring at room temperature. The reaction solution is then stirred for a further 30 minutes, then diluted with 200 ml of water, made alkaline with concentrated ammonia and shaken three times with chloroform. The organic phase is evaporated, the residue is purified by column chromatography over silica gel with chloroform-ethyl acetate (5:1) and 2-amino-3-bromo-5-tert.butyl-N-cyclohexyl-N-methyl-benzylamine hydrochloride is crystallized from ethanol-ether with the addition of ethanolic hydrochloric acid.

Melting point: 214-215°C (dec.).

Example 11

5- acetyl- 2- amino- 3- bromo- N, N- dimethyl- benzylamine

Dissolve 12.8 g of 5-acetyl-2-amino-N,N-dimethyl-benzylamine hydrochloride in 100 ml of 80% acetic acid and add 9.0 g of bromine dropwise. The reaction mixture is then made alkaline with 2N ammonia, shaken twice with chloroform and the organic phase evaporated. By recrystallization of the residue from ethanol-water, 5-acetyl-2-amino-3-bromo-N,N-dimethyl-benzylamine with melting point 92-95°C is obtained.

Example 12

2- amino- 5- chloro- N- cyclohexyl- N- methyl- 3- trifluoromethyl- benzylamine

A solution of 9.5 g of 2-amino-N-cyclohexyl-N-methyl-3-trifluoromethyl-benzylamine and 3 ml of pyridine in 40 ml of tetrahydrofuran is cooled to -10°C and added with stirring at this temperature during 20 minutes a solution of 9.1 g of phenyliododichloride in 80 ml of tetrahydrofuran. It is stirred for a further 4.5 hours at 0 to -10 C and the mixture is then allowed to stand for 18 hours at approx. 20°C. It is diluted with water and shaken with chloroform. The organic phase is washed with potassium carbonate solution and water. After drying over magnesium sulfate, the solution is evaporated in vacuo, the oily residue is taken up in ethyl acetate and the hydrochloride of the aforementioned compound is precipitated with isopropanolic hydrochloric acid. After three recrystallizations from ethanol using activated carbon, colorless crystals are obtained. Melting point: 260-262°C.

Example 13

2- amino- N, N- diethyl- 3- methyl- benzylamine

8 g of 2-acetylamino-N,N-diethyl-3-methyl-benzylamine are dissolved in

300 ml of 2N hydrochloric acid, boiled for 14 hours under reflux, the solution is de-coloured with activated charcoal and made alkaline with concentrated ammonia. The mixture is extracted three times with chloroform, the organic phase is evaporated and the residue is purified by column chromatography over silica gel with ethyl acetate. The crude base is dissolved in acetone-ethanol and neutralized with ethanolic hydrochloric acid, whereby 2-amino-N,N-diethyl-3-methyl-benzylamine hydrochloride crystallizes out.

Melting point: 182-184°C.

Example 14

2- amino- 5- bromo- N, N- diethyl- 3- diethylamino" ethyl- benzylamine

Dissolve 11.5 g of 2-acetylamino-5-bromo-N,N-diethyl-3-diethylaminomethyl-benzylamine in 250 ml of 2N hydrochloric acid, boil for 14 hours under reflux and then decolorize with activated charcoal. The filtrate is made alkaline with concentrated ammonia, extracted three times with chloroform and the organic phase is evaporated. The residue is purified by column chromatography over silica gel with chloroform-ethyl acetate (1:2). The combined fractions are evaporated, the residue is dissolved in absolute ethanol and slightly acidified with absolute ethanolic hydrochloric acid, after which 2-amino-5-bromo-N,N-diethyl-3-diethylaminomethyl-benzylamine is crystallized as dihydrochloride. Melting point: 213.5-215°C (dec.).

Example 15

2- amino- 5- bromo- 4- tert. butyl-N-cyclohexyl-N-methyl-benzylamine

5 g of 2-acetylamino-5-bromo-4-tert.butyl-N-cyclohexyl-N-methyl-benzylamine are boiled in 50 ml of ethanol and 50 ml of concentrated hydrochloric acid for 15 hours at reflux, then made alkaline with concentrated ammonia and shaken three times times with chloroform. The organic phase is evaporated, the residue is purified by column chromatography over silica gel with ethyl acetate and 2-amino-5-bromo-4-tert.butyl-N-cyclohexyl-N-methyl-benzylamine is crystallized from ethanol-ether with the addition of ethanolic hydrochloric acid as hydrochloride.

Melting point: 202-202.5°C (dec.).

Example 16

2- amino- 5- tert- butyl- N- cyclohexyl- N- methyl- benzylamine

15 g of 2-acetylamino-5-tert.butyl-N-cyclohexyl-N-methyl-benzylamine in 0.5 1 4N hydrochloric acid is boiled for 14 hours at reflux. It is then made alkaline with concentrated ammonia, the solution is shaken three times with chloroform and the organic phase is evaporated. The crude product is purified by column chromatography over silica gel with ethyl acetate and 2-amino-5-tert.butyl-N-cyclohexyl-N-methyl-benzylamine is crystallized as hydrochloride from acetone-ether with ethanolic hydrochloric acid. Melting point: 144-146°C.

Example 17

4- amino- 3- tert. butyl-N-cyclohexyl-N-methyl-benzylamine

20 g of 4-acetylamino-3-tert.butyl-N-cyclohexyl-N-methyl-benzylamine in 200 ml of 3N hydrochloric acid are boiled for 6 hours at reflux, then made alkaline with concentrated ammonia and the organic phase is evaporated. 4-amino-3-tert.butyl-N-cyclohexyl-N-methyl-benzylamine is crystallized from absolute ethanol ether as dihydrochloride after addition of absolute ethanolic hydrochloric acid.

Melting point: 197-199°C (dec.).

Example 18

5- acetyl- 2- amino- N, N- dimethyl- benzylamine

22.5 g of 5-acetyl-2-acetylamino-N,N-dimethyl-benzylamine is dissolved

in a solution of 8 g of sodium hydroxide in 400 ml of 50% ethanol and heated for 5 hours to 7Q-80°C. The reaction solution is then diluted with water, extracted three times with chloroform and the organic phase is evaporated. The residue is dissolved in absolute ethanol and neutralized with absolute ethanolic hydrochloric acid, after which 5-acetyl-2-amino-N,N-dimethyl-benzylamine hydrochloride is crystallized. Melting point: 209-215°C (dec.).

Example 19

N-[ 2- amino- 3- bromo- 5-( 1- hydroxyethyl)- benzyl]- hexamethyleneamine

9 g of N-(5-acetyl-2-amino-3-bromo-benzyl)-hexamethyleneamine are dissolved in 250 ml of ethanol and 100 ml of water, 6 g of sodium borohydride are added in portions while stirring and allowed to stand for 15 hours. The reaction solution is then diluted with 300 ml of water, shaken three times with chloroform, the organic phase is extracted with water and evaporated. The residue is purified by column chromatography over silica gel with ethyl acetate, whereby N-[2-amino-3-bromo-5-(1-hydroxyethyl)-benzyl]-hexamethyleneamine is obtained in crystalline form and recrystallized from isopropanol. Melting point: 110-112°C.

Example 20

N- ethyl- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

13 g of N-ethyl-2-amino-3-bromo-5-carbethoxy-N-cyclohexyl-benzylamine are boiled with 100 ml of 6N hydrochloric acid for one hour. The obtained oil precipitate is then decanted and the solution is evaporated to dryness. The residue is recrystallized from methanol. N-ethyl-2-amino-3-bromo-5-carboxy-N-cyclohexyl-benzylamine hydrochloride with melting point 227-229°C is obtained.

Example 21

2- amino- 3- bromo- 4- carbamoyl- N, N- diethyl- benzylamine

11 g of 2-amino-3-bromo-5-cyano-N,N-diethyl-benzylamine are boiled with 70 ml of ethanol and 100 ml of 5N caustic soda at reflux. After cooling, dilute with 100 ml of water and extract with chloroform. The chloroform extract is dried over sodium sulfate and the residue is recrystallized from isopropanol. 2-amino-3-bromo-5-carbamoyl-N,N-diethyl-benzylamine with melting point 140-142°C is obtained.

Example 22

2- acetamido- 3- bromo- 5- carbetoxy- N, N- diethyl-. benzylamine

1 g 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine

dissolve in 2 ml of acetyl chloride and heat for 1 hour at 50°C. The acetyl chloride is evaporated in vacuo, the residue is distributed between cold dilute ammonia and chloroform, the chloroform solution is evaporated, the product is purified by chromatography on silica gel (eluent: ethyl acetate), the evaporation residue from the eluate is dissolved in isopropanol and 2-acetamino-3-bromo-5-carbethoxy- N,N-diethyl-benzylamine hydrochloride is caused to crystallize by the addition of isopropanolic hydrochloric acid. Melting point: 190-194°C.

Example 23

2- acetamirio- 3- bromo- N, N- diethyl- 5- methyl- benzylamine

1.53 g of 2-amino-3-bromo-N,N-diethyl-5-methyl-benzylamine hydrochloride are dissolved in 50 ml of acetic anhydride at 75°C. It is evaporated to dryness in vacuo and the residue is recrystallized from ethanol. The 2-acetamino-3-bromo-N,N-diethyl-5-methyl-benzylamine hydrochloride obtained melts at 170-172°C.

. Example 2 4

2- acetamino- 3- bromo- N, 5- dimethyl- N-( trans- 4- hydroxycyclohexyl)-benzylamine

2.2 g of 2-amino-3-bromo-N,5-dimethyl-N-(trans-4-hydroxycyclohexyl)-benzylamine are dissolved in 100 ml of methanol and heated to boiling.

Over the course of 2 hours, 75 ml of acetic anhydride are added and the acetic acid methyl ester thus obtained is distilled off. It is evaporated to dryness in a vacuum and the evaporation is repeated after adding more methanol. The residue obtained is dissolved in ethanol and transferred to 2-acetamino-3-bromo-N,5-dimethyl-N-(trans-4-hydroxycyclohexyl)-benzylamine hydrochloride with ethanolic hydrochloric acid.

Melting point: 246-248°C.

Example 25

2- acetamino- 5- carbethoxy- N, N- diethyl- benzylamine

30 g of 2-acetamino-5-carbethoxy-benzyl bromide are dissolved in 400 ml of chloroform and 100 ml of ethanol and refluxed for 1 hour with 22 g of diethylamine. It is cooled, evaporated in vacuo, the residue is distributed between dilute ammonia and chloroform, the chloroform solution is dried over sodium sulphate and evaporated in vacuo. The residue is purified by chromatography on silica gel (eluent: ethyl acetate). The 2-acetamino-5-carbethoxy-N,N-diethyl-benzylamine obtained is recrystallized from ethanol.

Melting point: 57-59°C..

Example 26

2- amino- N- cyclohexyl- N- methyl- 3- trifluoromethyl- benzylamine

Dissolve 20 g of 2-amino-3-trifluoromethyl-benzyl alcohol in 200 ml

chloroform and add 15.9 ml of thionyl chloride dropwise over 10 minutes with stirring. It is then boiled for a further 90 minutes under reflux. It is cooled and all volatiles are carefully removed under vacuum. The residue of crude benzyl chloride obtained is dissolved in 200 ml of chloroform. Under mechanical stirring and ice-cooling, 38.1 g of N-methyl-cyclohexylamine are added within 10 minutes and then the mixture is allowed to stand for 18 hours at approx. 20°C. It is washed with saturated potassium carbonate solution, dried and the solvent is removed in vacuo. The oil residue is purified by chromatography over a silica gel column (eluent: chloroform:methanol = 9:1). The obtained, again oily evaporation residue is dissolved in a mixture of ether and ethyl acetate ( 1:1). Upon addition of isopropanolic hydrochloric acid, 2-amino-N-cyclohexyl-N-methyl-3-trifluoromethyl-benzylamine hydrochloride precipitates as crystals. After two recrystallizations from isopropanol, the melting point is 203-206°C.

Example 27

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

Dissolve 80 g of 2-amino-5-carbethoxy-N,N-diethyl-benzylamine in 300 ml of glacial acetic acid and 30 ml of water and add dropwise at room temperature and stirring a solution of 40 g of bromine in 40 ml of glacial acetic acid. The solution is allowed to stand for one hour, it is poured onto ice, made alkaline with ammonia and extracted with chloroform. The combined chloroform solutions are evaporated to dryness in vacuo. The crude product obtained is purified by chromatography on silica gel (eluent: ethyl acetate) and transferred to 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine hydrochloride with isopropanolic hydrochloric acid, which is recrystallized from ethanol.

Melting point: 165-168°C.

Example 28

2- amino- 3- bromo- 5- cyano- N- cyclohexyl- N- methyl- benzylamine

7 g of 2-amino-5-cyano-N-cyclohexyl-N-methyl-benzylamine are dissolved

in 100 ml of 90% acetic acid and add drop by drop while stirring

solution of 4 g of bromine in 4 ml of glacial acetic acid. It is stirred for one hour at room temperature and for a further 30 minutes at 60°C, cooled, poured onto ice, made alkaline with ammonia, shaken out three times with chloroform, the chloroform solution evaporated in vacuo, the residue dissolved in ethanol and 2-amino-3- bromo-5-cyano-N-cyclohexyl-N-methyl-benzylamine hydrochloride is brought to crystallisation by the addition of ethanolic hydrochloric acid.

Melting point: 236-240°C.

Example 29

2- amino- 5- chloro- N- cyclohexyl- 3- methoxy- N- methyl- benzylamine

11 g 2-amino-N-cyclohexyl-3-methoxy-N-methyl-benzylamine

dissolve in 100 ml of glacial acetic acid and quickly add a solution of 2.8 g of chlorine in 50 ml of glacial acetic acid while stirring at room temperature. After the addition has been completed, the mixture is immediately poured into a sodium hydrogen sulphite solution, ice is added and made alkaline with 1L caustic soda. The resulting precipitate is extracted with chloroform, the chloroform phase is washed with water, dried over sodium sulphate and evaporated to dryness in vacuo. The residue is chromatographed over silica gel with chloroform: ethyl acetate (3:1). The crude product obtained is dissolved in absolute ethanol and acidified with ethereal hydrochloric acid to pH 5-6 and petroleum ether is added. The separated hydrochloride is suctioned off and washed with a little petroleum ether.

Melting point: 189-193°C (dec.).

Example 30

2- amino- 5- bromo- N- cyclohexyl- N- methyl- 3- trifluoromethyl- benzylamine

9.5 g of 2-amino-N-cyclohexyl-N-methyl-3-trifluoromethyl-benzylamine are dissolved in 140 ml of 70% acetic acid and 5.5 g of bromine in 30 ml of glacial acetic acid are added during 5 minutes while stirring. After 90 minutes, excess bromine is destroyed with sodium hydrogen sulphite solution and the solution is then evaporated in a vacuum. The residue is distributed between ethyl acetate and saturated potassium carbonate solution. The organic phase is dried and re-evaporated in vacuo. The remaining oil is dissolved in a mixture of ether and ethyl acetate (1:1) and the hydrochloride of the above-mentioned compound is precipitated by the addition of isopropanolic hydrochloric acid. After recrystallization from ethanol twice, the melting point is 259-261°C.

Example 31

2-amino-5-carbethoxy-N,N-diethyl-benzylamine

Dissolve 19 g of 2-acetamino-5-carbethoxy-N,N-diethyl-benzylamine in 100 ml of ethanol and boil for one hour under reflux after adding 60 ml of concentrated hydrochloric acid. The mixture is poured onto ice, made alkaline with ammonia, shaken three times with chloroform, the chloroform solution is dried over sodium sulfate, evaporated in vacuo, the crude product is purified by chromatography on silica gel (eluent: ethyl acetate) and with isopropanolic hydrochloric acid, 2-amino-5-carbethoxy-N,N-diethyl-benzylamine hydrochloride is obtained, which is recrystallized from ethanol.

Melting point: 138-142°C.

Example 32

2- amino- 5- carboxy- N- cyclohexyl- N- methyl- benzylamine.

21 g of 2-acetamino-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine are boiled with 100 ml of ethanol, 90 ml of water and 60 ml of concentrated hydrochloric acid for one hour under reflux. It is cooled, poured onto ice, made alkaline with ammonia, extracted three times with chloroform, the ammoniacal phase is evaporated to dryness in vacuo, the residue is stirred thoroughly with ethanol, filtered, the filtrate is evaporated to dryness in vacuum and the residue is recrystallized from ethanol. 2-amino-5-carboxy-N-cyclohexyl-N-methyl-benzylamine with melting point 200-205°C is obtained

Example 33

2-amino-5-carbamoyl-N,N-diethyl-benzylamine

10 g of 2-acetamino-5-cyano-N,N-diethyl-benzylamine are boiled in

4 hours with 100 ml 5n caustic soda and 70 ml ethanol. It is cooled, diluted with 200 ml of water and extracted three times with 250 ml of chloroform each time. The chloroform solution is dried over sodium sulfate and evaporated in vacuo. The residue is recrystallized from ethanol. 2-amino-5-carbamoyl-N,N-diethyl-benzylamine with melting point 129-131°C is obtained.

Example 34

2- amino- N- ethyl- N- cyclohexyl- 5- methyl- benzylamine

2 g of 2-acetamino-N-ethyl-N-cyclohexyl-5-methyl-benzylamine are heated with 50 ml of concentrated hydrochloric acid for 1.5 hours at 90°C. The mixture is cooled, poured onto ice, fermented alkaline with caustic soda, extracted with chloroform, the chloroform solution is evaporated in vacuo, the residue is dissolved in ethanol, it is obtained with ethanolic hydrochloric acid 2-amino-N-ethyl-N-cyclohexyl-5-methyl-benzylamine hydrochloride .

Melting point: 189-191°C (dec.).

Example 35

2- amino- 3- chloro- N- cyclohexyl- 5- fluoro- N- methyl- benzylamine

To a suspension of 3.8 g of lithium aluminum hydride in 200 ml of absolute ether, a solution of 9.1 g of 2-amino-3-chloro-N-cyclohexyl-5-fluoro-N-methyl-benzamide in 300 ml of absolute ether is added dropwise while stirring . After completion of the addition, it is heated for one hour to the reflux temperature, then cooled in an ice bath and excess lithium aluminum hydride is decomposed under nitrogen as protective gas carefully with water. The organic solution is decanted from the precipitate and dried over sodium sulphate. On acidification with ethereal hydrochloric acid, 2-amino-3-chloro-N-cyclohexyl-5-fluoro-N-methyl-benzylamine precipitates as hydrochloride, which is recrystallized from absolute ethanol/ether.

Melting point: 190-192°C.

Example 36

2- amino- N- tert. butyl-5-carbethoxy-benzylamine

3.4 g of 2-amino-N-benzyl-N-tert.butyl-5-carbethoxy-benzylamine are dissolved in 50 ml of ethanol. Ethanolic hydrochloric acid is added until the pH is approx. 2 is obtained, and is hydrated in the presence of palladium (10%) on charcoal. After absorption of 1 mol of hydrogen, the hydrogenation is interrupted, the catalyst is filtered off, evaporated to dryness in a vacuum and the residue is distributed between dilute ammonia and chloroform. The chloroform solution is dried, evaporated to dryness and the residue recrystallized from ethanol, whereby 2-amino-N-tert.butyl-5-carbethoxy-benzylamine with a melting point of 77-79°C is obtained.

Example 37

2-acetamino-N-tert. butyl-5-carbethoxy-benzylamine

Melting point: 136-139°C*

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and tert-butylamine analogously to example 25.

Example 38

2- amino- N- tert. butyl-5-carbethoxy-benzylamine

Melting point: 77-79°C.

Prepared by saponification of 2-acetamino-N-tert.butyl-5-carbethoxy-benzylamine in ethanolic hydrochloric acid analogously to example 31.

Example 39

2- amino- 3- bromo- N- tert. butyl-5-carbethoxy-benzylamine Melting point: 78-81°C.

Prepared from 2-amino-N-tert.butyl-5-carbethoxy-benzylamine and bromine analogously.Example 27.

Example 40

2- acetamino- 5- carbethoxy- N- cyclohexyl- N- methyl- benzylamine Melting point: 71-74°C.

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and N-methyl-cyclohexylamine analogous to example 25.

Example 41

2- amino- 5- carbetoxy- N- cyclohexyl- N- methyl- benzylamine The melting point of the hydrochloride: 160-170°C.

Prepared by saponification of 2-acetamino-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine in ethanolic hydrochloric acid analogously to example 31.

Example 42

2- amino- 3- bromo- 5- carbetoxy- N- cyclohexyl- N- methyl- benzylamine Melting point of the hydrochloride: 212-215°C.

Prepared from 2-amino-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine and bromine analogous to example 27.

Example 4 3

2- amino- 5- carbetoxy- 3- chloro- N- cyclohexyl- N- methyl- benzylamine Melting point of the hydrochloride: 207-209°C.

Prepared from 2-amino-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine and chlorine analogous to example 27.

Example 4 4

2- acetamino- 3- bromo- 5- carbetoxy- N- cyclohexyl- N- methyl- benzylamine Melting point: 220-223°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine and acetyl chloride analogously to example 22.

Example 45

2- acetamino- N- ethyl- 5- carbetoxy- N- cyclohexyl- benzylamine Melting point: 92-95°C. v

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and N-ethyl-cyclohexylamine analogously to example 25.

Example 46.

N- ethyl- 2- amino- 5- carbethoxy- N- cyclohexyl- benzylamine Melting point of the dihydrochloride: 188-194°C.

Prepared by saponification of 2-acetamino-N-ethyl-5-carbethoxy-N-cyclohexyl-benzylamine in ethanolic hydrochloric acid analogously to example 31.

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Example 47

N- ethyl- 2- amino- 3- bromo- 5- carbethoxy- N- cyclohexyl- benzylamine Melting point: 66-68°C.

Prepared from N-ethyl-2-amino-5-carbethoxy-N-cyclohexyl-benzylamine and bromine analogous to example 27.

Example 48

N- ethyl- 2- amino- 5- carbetoxy- 3- chloro- N- cyclohexyl- benzylamine The melting point of the hydrochloride: 165-170°C.

Prepared from N-ethyl-2-amino-5-carbethoxy-N-cyclohexyl-benzylamine and chlorine analogous to example 27.

Example 49-

N-(2-acetamino-5-carbethoxy-benzyl)-hexamethyleneamine

Melting point: 100-102°C.

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and hexamethyleneamine analogously to example 25.

Example 50

2- amino- N- tert. butyl-5-carbamoyl-benzylamine

Melting point of the hydrochloride: 120-130°C.

Prepared by saponification of 2-acetamino-N-tert.butyl-5-cyano-benzylamine in caustic soda analogously to example 33.

Example 51

2- amino- 3- bromo- N- tert. butyl-5-carbamoyl-benzylamine

Melting point of the hydrochloride: 160-170°C.

Prepared by saponification of 2-amino-3-bromo-N-tert.butyl-5-cyano-benzylamine in caustic soda analogous to example 21.

Example 52

2- amino- 5- carbamoyl- N- cyclohexyl- N- methyl- benzylamine Melting point: 142-143°C.

Prepared by saponification of 2-amino-5-cyano-N-cyclohexyl-N-methylbenzylamine in caustic soda analogous to example 21.

Example 53

2- amino- 3- bromo- 5- carbamoyl- N- cyclohexyl- N- methyl- benzylamine Melting point: 150-152°C.

Prepared by saponification of 2-amino-3-bromo-5-cyano-N-cyclohexyl-N-methyl-benzylamine in caustic soda analogous to example 21.

Example 54

2-acetamino-3-bromo-5-carbamoyl-N-cyclohexyl-N-methyl-benzylamine

Melting point: 185-190°C

Prepared from 2-amino-3-bromo-5-carbamoyl-N-cyclohexyl-N-methyl-benzylamine and acetyl chloride analogously to example 22.

Example 55

N- ethyl- 2- amino- 5- carbamoyl- N- cyclohexyl- benzylamine Melting point: 136-138°C.

Prepared by saponification of N-ethyl-2-acetamino-5-cyano-N-cyclohexylbenzylamine in caustic soda analogous to example 33.

Example 56

N- ethyl- 2- amino- 3- bromo- 5- carbamoyl- N- cyclohexyl- benzylamine Melting point: 144-146°C.

Prepared by saponification of N-ethyl-2-amino-3-bromo-5-cyano-N-cyclohexyl-benzylamine in caustic soda analogous to example 21.

Example 57

N-(2-amino-5-carbamoyl-benzyl)-hexamethyleneamine

Melting point: 115-118°C..

Prepared by saponification of N-(2-amino-5-cyano-benzyl)-hexamethyleneamine in caustic soda analogously to example 21.

Example 58

N-(2-amino-3-bromo-5-carbamoyl-benzyl)-hexamethyleneamine Melting point: 155-157°C.

Prepared by saponification of N-(2-amino-3-bromo-5-cyano-benzyl)-hexamethyleneamine in caustic soda analogously to example 21.

Example 59

2-amino-5-carboxy-N,N-diethyl-benzylamine

Melting point of the hydrochloride: 194-198°C.

Prepared by saponification of 2-amino-5-carbethoxy-N,N-diethyl-benzylamine in hydrochloric acid analogously to example 20.

Example 60

2- amino- 3- bromo- 5- carboxy-^ I, N- diethyl- benzylamine Melting point of the hydrochloride: 233-234°C (dec.).

Prepared from 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine by saponification in hydrochloric acid analogously to example 20.

Example 61

2- amino- N- tert. butyl-5-carboxy-benzylamine Hydrochloride melting point: 220-230°C.

Prepared by saponification of 2-acetamino-N-tert.butyl-5-carbethoxy-benzylamine in hydrochloric acid analogously to example 32.

Example 62

2- amino- 3- bromo- N- tert. butyl-5-carboxy-benzylamine The melting point of the hydrochloride: 270-280°C (decomp.).

Prepared by saponification of 2-amino-3-bromo-N-tert.butyl-5-carbethoxy-benzylamine in hydrochloric acid analogously to example 20.

Example 63

2- acetamino- 5- carboxy- N- cyclohexyl- N- methyl- benzylamine The melting point of the hydrochloride: 228-232°C.

Prepared from 2-amino-5-carboxy-N-cyclohexyl-N-methyl-benzylamine and acetyl chloride analogously to example 22.

Example 64

2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- N- methyl- benzylamine The melting point of the hydrochloride: 230-240°C.

Prepared by saponification of 2-amino-3-bromo-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine in hydrochloric acid analogously to example 20.

Example 65

N- ethyl- 2- amino- 5- carboxy- N- cyclohexyl- benzylamine Melting point of the dihydrochloride: 175-181°C.

Prepared by saponification of N-ethyl-2-amino-5-carbethoxy-N-cyclohexyl-benzylamine in hydrochloric acid analogously to example 20.

Example 66

N- ethyl- 2- amino- 5- carboxy- 3- chloro- N- cyclohexyl- benzylamine The melting point of the hydrochloride: 228-232°C.

Prepared by saponification of N-ethyl-2-amino-5-carbethoxy-3-chloro-N-cyclohexyl-benzylamine in hydrochloric acid analogously to example 20.

Example 6 7

2- acetamino- 5- cyano- N/ N- dimethyl- benzylamine

melting point of the hydrochloride: 244-245°C (dec.).

Prepared from 2-acetamino-5-cyano-benzyl bromide and dimethylamine analogously to example 25.

Example 68

2- amino- 5- cyano- N, N- dimethyl- benzylamine

Melting point of the hydrochloride: 240-241°C.

Prepared by saponification of 2-acetamino-5-cyano-N,N-dimethyl-benzylamine in hydrochloric acid analogously to example 34.

Example 69

2- amino- 3- bromo- 5- cyano- N, N- dimethyl- benzylamine

Melting point of the hydrochloride: 250-255°C (dec.).

Prepared from 2-amino-5-cyano-N,N-dimethyl-benzylamine and bromine analogously to example 28.

Example 70

2- acetamino- 5- cyano- N, N- diethyl- benzylamine

Melting point: 80-82°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and diethylamine analogously to example 25.

Example 71

2-amino-5-cyano-N,N-diethyl-benzylamine

Melting point of the hydrochloride: 241-244°C.

Prepared by saponification of 2-acetamino-5-cyano-N,Nf-diethyl-benzylamine in hydrochloric acid analogously to example 34.

Example 72

2- amino- 3- bromo- 5- cyano- N, N- diethyl- benzylamine Melting point of the hydrochloride: 226-229°C.

Prepared from 2-amino-5-cyano-N,N-diethyl-benzylamine and bromine analogous to example 28.

Example 73

2- acetamino- 5- cyano- N, N- dipropyl- benzylamine.

Melting point: 80-82°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and dipropylamine analogous to example 25.

Example 74

2- amino- 5- cyano- NyN- dipropyl- benzylamine

Melting point of the hydrochloride: 215-219°C.

Prepared by saponification of 2-acetamino-5-cyano-N,N-dipropyl-benzylamine in hydrochloric acid analogously to example 34.

Example 75

2-acetamino-N-tert. butyl-5-cyano-benzylamine Hydrochloride melting point: 260-265°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and tert-butylamine analogously to example 25.

Example 76

2- amino- N- tert. butyl-5-cyano-benzylamine

Melting point of the hydrochloride: 233-238°C.

Prepared by saponification of 2-acetamino-N-tert.butyl-5-cyano-benzylamine in hydrochloric acid analogously to example 34.

Example 77

2- amino- 3- bromo- N- tert. butyl-5-cyano-benzylamine Melting point: 78-80°C.

Prepared from 2-amino-N-tert.butyl-5-cyano-benzylamine and bromine analogously to example 28.

Example 78

2- acetamino- 5- cyano- N- cyclohexyl- N- methyl- benzylamine Melting point: 116-118°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and N-methyl-cyclohexylamine analogous to example 25.

Example 79

2- amino- 5- cyano- N- cyclohexyl- N- methyl- benzylamine Melting point of the hydrochloride: 207-211°C.

Prepared by saponification of 2-acetamino-5-cyano-N-cyclohexyl-N-methyl-benzylamine in hydrochloric acid analogously to example 34.

Example 80

2- acetamino- 3- bromo- 5- cyano- N- cyclohexyl- N- methyl- benzylamine Melting point: 101-103°C

Prepared from 2-amino-3-bromo-5-cyano-N-cyclohexyl-N-methyl-benzylamine and acetyl chloride analogously to example 22.

Example 81

2- acetamino- N- ethyl- 5- cyano- N- cyclohexyl- benzylamine Melting point: 85-88°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and N-ethyl-cyclohexylamine analogous to example 25.

Example 82

2- amino- N- ethyl- 5- cyano- N- cyclohexyl- benzylamine The melting point of the dihydrochloride: 201-206°C.

Prepared by saponification of 2-acetamino-N-ethyl-5-cyano-N-cyclohexyl-benzylamine in hydrochloric acid analogously to example 34.

Example 83

N- ethyl- 2- amino- 3- bromo- 5- cyano- N- cyclohexyl- benzylamine Melting point of the hydrochloride: 194-197°C.

Prepared from N-ethyl-2-amino-5-cyano-N-cyclohexyl-benzylamine and bromine analogous to example 28.

Example 84 2-acetamino-N-ethyl-N-benzyl-5-cyano-benzylamine Melting point: 112-113°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and N-ethyl-benzylamine analogously to example 25.

Example 85

2- amino- N- ethyl- N- benzyl- 5- cyano- benzylamine Melting point: 107-108°C.

Prepared by saponification of 2-acetamino-N-ethyl-N-benzyl-5-cyano-benzylamine in hydrochloric acid analogously to example 34.

Example 86

N- ethyl- 2- amino- N- benzyl- 3- bromo- 5- cyano- benzylamine Melting point: 89-90°C.

Prepared from N-ethyl-2-amino-N-benzyl-5-cyano-benzylamine and bromine analogous to example 28.

Example 87

2- acetamino- N- benzyl- 5- cyano- N- propyl- benzylamine Melting point: 109-111°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and N-propyl-benzylamine analogously to example 25.

Example 88

2- amino- N- benzyl- 5- cyano- N- propyl- benzylamine Melting point: 63-64°C.

Prepared by saponification of 2-acetamino-N-benzyl-5-cyano-N-propyl-benzylamine in hydrochloric acid analogously to example 34.

Example 89

2- amino- N- benzyl- 3- bromo- 5- cyano- N- propyl- benzylamine Melting point: 96-98°C.

Prepared from 2-amino-N-benzyl-5-cyano-N-propyl-benzylamine and bromine analogous to example 28.

Example 90

2- acetamino- N- benzyl- N- butyl- 5- cyano- benzylamine Melting point: 65-66°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and N-butyl-benzylamine analogously to example 25.

Example 91

2- amino- N- benzyl- 3- bromo- N- butyl- 5- cyano- benzylamine Melting point: 71-73°C.

Prepared from 2-amino-N-benzyl-N-butyl-5-cyano-benzylamine and bromine analogous to example 28.

Example 92

N-(2-acetamino-5-cyano-benzyl)-hexamethyleneamine Melting point: 108-110°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide and hexamethyleneamine analogously to example 25.

Example 93

N-(2-amino-5-cyano-benzyl)-hexamethyleneamine

Melting point of the hydrochloride: 228-232°C.

Prepared by saponification of N-(2-acetamino-5-cyano-benzyl)-hexamethyleneamine in hydrochloric acid analogously to example 34.

Example 94

N-(2-amino-3-bromo-5-cyano-benzyl)- hexamethyleneamine The melting point of the hydrochloride: 172-176°C.

Prepared from N-(2-amino-5-cyano-benzyl)-hexamethyleneamine and bromine analogously to example 28.

Example 95

2- acetamino- 3- bromo- N, N, 5- trimethyl- benzylamine Melting point: 89-91°C.

Prepared from 2-amino-3-bromo-N,N,5-trimethyl-benzylamine and acetic anhydride analogously to example 2 3.

Example 96

2- amino- 3- bromo- N, N, 5- trimethyl- benzylamine Melting point of the hydrochloride: 216-217°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and dimethylamine analogously to example 1.

Example 97

2-acetamino-N-ethyl-3-bromo-N,5-dimethyl-benzylamine Melting point: 81-83°C.

Prepared from N-ethyl-2-amino-3-bromo-N,5-dimethyl-benzylamine and acetic anhydride analogously to example 2 3.

Example 98

2- amino- N- ethyl- 3- bromo- N, 5- dimethyl- benzylamine Melting point of the hydrochloride: 199-200°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and N-methyl-ethylamine analogously to example 1.

Example 99

2- acetamino- N, N- diethyl- 5- methyl- benzylamine The melting point of the hydrochloride: 184-186°C.

Prepared from 2-acetamino-5-methyl-benzyl bromide and diethylamine analogously to example 6.

Example 100

2- amino- N/ N- diethyl- 5- methyl- benzylamine

Melting point of the dihydrochloride: 193-195°C.

Prepared by saponification of 2-acetamino-N,N-diethyl-5-methyl-benzylamine in hydrochloric acid analogously to example 34.

Example 101

2- amino- 3- bromo- N, N- diety1- 5- methyl1- benzylamine

Melting point of the hydrochloride: 205-207°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and diethylamine analogously to example 1.

Example 102

2- acetamino- N- cyclohexyl- Nf 5- dimethyl- benzylamine

Melting point of the hydrochloride: 222-223°C.

Prepared from 2-acetamino-5-methyl-benzyl bromide and N-methyl-cyclohexylamine analogous to example 6.

Example 103

2-amino-N-cyclohexyl-N,5-dimethyl-benzylamine

Melting point of the dihydrochloride: 203-205°C.

Prepared by saponification of 2-acetamino-N-cyclohexyl-N,5-dimethylbenzylamine in hydrochloric acid analogously to example 34.

Example 104

2- amino- 3- bromo- N- cyclohexyl- N, 5- dimethyl- benzylamine Melting point of the hydrochloride: 223-224°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and N-methyl-cyclohexylamine analogous to example 1.

Example 105

2- acetamiho- 3- bromo- N, 5- dimethyl- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine

Melting point of the hydrochloride: 96-97°C.

Prepared from 2-amino-3-bromo-N,5-dimethyl-N-(cis-3-hydroxy-cyclohexyl)-benzylamine and acetic anhydride analogous to example 24.

Example 106

2- amino- 3- bromo- N, 5- dimethyl- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 198°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and N-methyl-cis-3-hydroxy-cyclohexylamine analogous to eczema]

Example 107

2- acetamino- N- ethyl- N- cyclohexyl- 5- methyl- benzylamine Melting point of the hydrochloride: 22 4-225°C.

Prepared from 2-acetamino-5-methyl-benzyl bromide and N-ethyl-cyclohexylamine analogous to example 6.

Example 108

2- amino- N- ethyl- 3- bromo- N- cyclohexyl- 5- methyl- benzylamine Melting point of the hydrochloride: 186°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and N-ethyl-cyclohexylamine analogously to example 1.

Example 109

2- amino- 3- bromo- N, 5- dimethyl- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine

Melting point of the hydrochloride: 212°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and N-methyl-trans-4-hydroxy-cyclohexylamine analogous to example 1.

Example 110

2- acetamino- N- benzyl- 3- bromo- N, 5- dimethyl- benzylamine

Melting point of the hydrochloride: 210-212°C.

Prepared from 2-amino-N-benzyl-3-bromo-N,5-dimethyl-benzylamine and acetic anhydride analogous to example 23.

Example 111

2- amino- N- benzyl- 3- bromo- N, 5- dimethyl- benzylamine

Melting point of the hydrochloride: 220-2'22°C.

Prepared from 2-amino-3-bromo-5-methylbenzyl alcohol, thionyl chloride and N-methyl-benzylamine analogously to example 1.

Example 112

N-(2-acetamino-3-bromo-5-methyl-benzyl)-pyrrolidine

Melting point of the hydrochloride: 197-198°C.

Prepared from N-(2-amino-3-bromo-5-methyl-benzyl)-pyrrolidine and acetic anhydride analogous to example 23.

Example 113

N-(2-amino-3-bromo-5-methyl-benzyl)-pyrrolidine

Melting point of the hydrochloride: 179-181°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and pyrrolidine analogous to example 1.

Example 114

N-(2-acetamino-3-bromo-5-methyl-benzyl)- piperidine The melting point of the hydrochloride: 252-253°C.

Prepared from N-(2-amino-3-bromo-5-methyl-benzyl)-piperidine and acetic anhydride analogously to example 23.

Example 115

N-(2-amino-3-bromo-5-methyl-benzyl)- piperidine

Melting point of the hydrochloride: 238-239°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and piperidine analogous to example 1.

Example 116

N-(2-amino-3-bromo-5-methyl-benzyl)-morpholine

Melting point of the hydrochloride: 243-244°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and morpholine analogous to example 1.

Example 117

N-(2-acetamino-5-methyl-benzyl)-hexamethyleneamine The melting point of the hydrochloride: 164-165°C.

Prepared from 2-acetamino-5-methyl-benzyl bromide and hexamethyleneamine analogously to example 6.

Example 118

N-(2-amino-5-methyl-benzyl)-hexamethyleneamine Dihydrochloride melting point: 205-207°C.

Prepared by saponification of N-(2-acetamino-5-methyl-benzyl)-hexamethyleneamine in hydrochloric acid analogously to example 34.

Example 119

N-(2- amino- 3- bromo- 5- methyl- benzyl)- hexamethylene amine The melting point of the hydrochloride: 193-194°C.

Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and hexamethyleneamine analogously to example 1.

Example 120

2- amino- 3- bromo- N, N- dimethyl- 5- methoxy- benzylamine

Prepared from 2-amino-N,N-dimethyl-5-methoxy-benzylamine and bromine analogous to example 9.

Evidence of structure by IR, UV and NMR spectra.

IR spectrum (methylene chloride):

3250 cm"1 NH2

34 cl cn-1 NH2

2780 cm"<1>N(CH3)2

2830 cm"<1>0CH3

1590 cm"<1>C=C

1600 cm"<1>C=C

Example 121

2-amino-N,N-dimethyl-5-methoxy-benzylamine

Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and dimethylamine analogously to example 1. Structural evidence by IR, UV and NMR spectra. IR spectrum (methylene chloride): 3280 cm"<1>NH9

-1

3420 cm NH2

2780 cm"<1>N(CH3)2

2830 cm"<1>0CH3

1600 cm"<1>C=C

Example 122

2-amino-N,N-diethyl-5-methoxy-benzylamine

Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and diethylamine analogous to example 1. Structural evidence by IR, UV and NMR spectra. IR spectrum (methylene chloride): 3260 cm"<1>NH0

-1

3410 cm NH2

2830 cm"<1>0CH3

2800 cm"<1>N-ethyl

1510 cm"<1>C=C

1600 cm"<1>C=C

Example 123

2- amino- 3- bromo- N, N- diethyl- 5- methoxy- benzylamine

Prepared from 2-amino-N,N-diethyl-5-methoxy-benzylamine and bromine analogous to example 9.

Evidence of structure by IR, UV and NMR spectra. IR spectrum (methylene chloride): 3250 cm"<1>NH2

3410 cm"<1>NH2

2830 cm"<1>0CH,

-1

2800 cm N-ethyl 1480 cm"<1>C=C

1590 cm"<1>C=C

Example 124

N-(2-amino-3-bromo-5-methoxy-benzyl)-morpholine

Prepared from N-(2-amino-5-methoxy-benzyl)-morpholine and bromine analogously to example 9.

Evidence of structure by IR, UV and NMR spectra. IR spectrum (methylene chloride).

3280 cm"<1>NH2

3420 cm"<1>NH2

2830 cm"<1>OCH,

-1

2810 cm N-alkyl

1480 cm"<1>C=C

1590 cm"<1>C=C

Example 125

2- amino- 3- bromo- N- cyclohexyl- 5- methoxy- N- methyl- benzylamine

Prepared from 2-amino-N-cyclohexyl-5-methoxy-N-methyl-benzylamine and bromine analogous to example 9. Structural evidence by IR and UV spectra. IR spectrum (methylene chloride): 32 40 cm<-1>NH23410 cm"<1>NH9-1 2860 cm aliphatic hydrocarbon 2940 cm 1 aliphatic hydrocarbon 2830 cm"<1>OCH,

-1

2800 cm N-alkyl

1480 cm"<1>C=C

1590 cm"<1>C=C

Example 126

N- ethyl- 2- amino- 3- bromo- N- cyclohexyl- 5- methoxy- benzylamine

Prepared from N-ethyl-2-amino-N-cyclohexyl-5-methoxy-benzylamine and bromine analogous to example 9. Structural evidence by IR, UV and NMR spectra. IR spectrum (methylene chloride): 32 40 cm"<1>NH2

3410 cm"1 NH-

2860 cm aliphatic hydrocarbon 2940 cm 1 aliphatic hydrocarbon 2830 cm"<1>OCH,

-1 J

2800 cm N-ethyl (shoulder)

in

1480 cm<-1>C=C

1590 cm<-1>C=C

Example 127

N-(2-amino-5-methoxy-benzyl)-morpholine

Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and morpholine analogous to example 1. Structural evidence by IR and UV spectra.

IR spectrum (methylene chloride):

3280 cm"<1>NH23410 cm-1NH~-1

2830 cm OCH-

-1

2800 cm N-alkyl

1500 cm"<1>C=C

1600 cm<-1>C=C

Example 128

2- amino- N- cyclohexy1- 5- methoxy- N- methyl1- ben zy1amine

Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and N-methyl-cyclohexylamine analogous to example 1. Structural evidence by IR and UV spectra.

IR spectrum (methylene chloride):

3240 cm'<1>NH9

-1

3400 cm NH-

-1

2780 cm N-methyl

2830 cm"1 OCH,

2850 cm aliphatic hydrocarbon

2930 cm 1 aliphatic hydrocarbon

1500 cm<-1>C=C

1510 cm<-1>C=C

Example 129

N- ethyl- 2- amino- N- cyclohexyl- 5- methoxy- benzylamine

Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and N-ethyl-cyclohexylamine analogous to example 1. Structural evidence by IR and UV spectra.

IR spectrum (methylene chloride):

3250 cm"<1>NH2

3400 cm"<1>NH2

2830 cm"<1>OCH,

-1

2800 cm N-ethyl (shoulder)

2850 cm 1 aliphatic hydrocarbon

2930 cm 1 aliphatic hydrocarbon

1500 cm<-1>C=C

1600 cm<-1>C=C

Example 130

N-(2-amino-3-bromo-5-methoxy-benzyl)- piperidine

Prepared from N-(2-amino-5-methoxy-benzyl)-piperidine and bromine analogously to example 9.

Evidence of structure by IR, UV and NMR spectra.

IR spectrum (methylene chloride):

3240 cm"<1>NH0

3400 cm NH2

2830 cm<-1>OCH,

-1 J

2790 cm N-alkyl

1480 cm"<1>C=C

1590 cm<-1>C=C

Example 131

N-(2-amino-5-methoxy-benzyl)-piperidine

Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and piperidine analogous to example 1.

Evidence of structure by IR and UV spectra.

IR spectrum (methylene chloride):

3260 cm"<1>NH0

-1

3410 cm NH2

2830 cm"1 0CH3

2800 cm"1 N-alkyl

1510 cm"<1>C=C

1600 cm<-1>C=C

Example 132

2- amino- 5- bromo- N- cyclohexyl- 3- methoxy- N- methyl- benzylamine Hydrochloride's melting point: 198-201°C.

Prepared from 2-amino-N-cyclohexyl-3-methoxy-N-methyl-benzylamine and bromine analogous to example 9.

Example 133

4- amino- 3- bromo- N- cyclohexyl- 5- methoxy- N- methyl- benzylamine Melting point of the hydrochloride: 177-180°C.

Prepared from 4-amino-N-cyclohexyl-5-methoxy-N-methyl-benzylamine and bromine analogous to example 9.

Example 134

N-(2-amino-5-fluoro-benzyl)-hexamethyleneamine

K?0.03: 96-100°C.

Prepared from 2-amino-5-fluoro-N-hexamethyleneamino-benzamide and lithium aluminum hydride analogously to Example 35.

Example 135

N-(2-amino-3-bromo-5-fluoro-benzyl)- hexamethyleneamine The melting point of the hydrochloride: 197-199°C.

Prepared from N-(2-amino-5-fluoro-benzyl)-hexamethyleneamine and bromine analogously to example 9.

Example 136

N-(2-amino-3-bromo-5-fluoro-benzyl)-morpholine

Melting point of the hydrochloride: 230-2 32°C.

Prepared from N-(2-amino-5-fluoro-benzyl)-morpholine and bromine analogous to example 9.

Example 137

2- amino- 3- bromo- N, N- diethyl- 5- fluoro- benzylamine Melting point of the hydrochloride: 182-184°C.

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and diethylamine analogously to example 1.

Example 138

N- ethyl- 2- amino- 3- bromo- N- cyclohexyl- 5- fluoro- benzylamine Melting point of the hydrochloride: 176-178°C.

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and N-ethyl-cyclohexylamine analogously to example 1.

Example 139

N- ethyl- 2- amino- 3- bromo- 5- fluoro- benzylamine

Melting point of the hydrochloride: 210-212°c.

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and ethylamine analogously to example 1.

Example 140

2- amino- 3- bromo- N, N- dimethyl- 5- fluoro- benzylamine Melting point of the hydrochloride: 241-243°C.

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and dimethylamine analogous to example 1..

Example 141

2- amino- 3- bromo- N- cyclohexyl- 5- fluoro- benzylamine

Melting point of the hydrochloride: 250-252°C (dec.).

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and cyclohexylamine analogously to example 1.

Example 142

2- amino- 3- bromo- 5- fluoro- N- methyl- benzylamine

Melting point of the hydrochloride: 215-217°C (dec.).

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and methylamine analogously to example 1.

Example 143

2- acetylamino- 5- bromo- N- cyclohexyl- N- methyl- 3-( N- methyl- cyclohexyl-aminomethyl)- benzylamine

Melting point: 194-199°C.

Prepared from 2-acetylamino-5-bromo-3-bromomethyl-benzyl bromide and N-methyl-cyclohexylamine analogously to example 3.

Example 144

2- acetylamino- 5- bromo- N-( trans- 4- hydroxy- cyclohexyl)- N- methyl- 3-[ N- methyl-( trans- 4- hydroxy- cyclohexylamino)- methyl]- benzylamine Melting point: 208-209 °C.

Prepared from 2-acetylamino-5-bromo-3-bromomethyl-benzyl bromide and trans-4-methylamino-cyclohexanol analogous to example 3.

Example 145

2- amino- N, N- diethyl- 3- diethylaminomethyl- benzylamine

Melting point of the dihydrochloride: 199-201°C (dec.).

Prepared by saponification of 2-acetylamino-N,N-diethyl-3-diethylaminomethyl-benzylamine in 2n hydrochloric acid analogously to example 14.

Example 146

2- amino- 5- bromo- N-( trans- 4- hydroxy- cyclohexyl)- N- methyl- 3-[ N- methyl—

(trans-4-hydroxy-cyclohexylamino)-methyl]-benzylamine

Melting point: 179-180°C.

Prepared by saponification of 2-acetylamino-5-bromo-N-(trans-4-hydroxy-cyclohexyl)-N-methyl-3-[N-methyl-(trans-4-hydroxy-cyclohexylamino)-methyl]-benzylamine in 2n hydrochloric acid analogous to example 14.

Example 147

2- acetylamino- N, N, 3- trimethyl- benzylamine

Melting point of the hydrochloride: 162-164°C.

Prepared from 2-acetylamino-3-methyl-benzyl bromide and dimethylamine analogously to example 2.

Example 148

2- acetylamino- N- ethyl- N, 3- dimethyl- benzylamine The melting point of the hydrochloride: 168-170°C.

Prepared from 2-acetylamino-3-methyl-benzyl bromide and N-methyl-ethylamine analogously to example 2.

Example 149

2- acetylamino- N, N- dipropyl- 3- methyl- benzylamine Melting point of the hydrochloride: 156-159°C.

Prepared from 2-acetylamino-3-methyl-benzyl bromide and dipropylamine analogous to example 2.

Example 150

2- acetylamino- 5- bromo- N, N, 3- trimethyl- benzylamine Melting point: 114-116°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and dimethylamine analogously to example 2.

Example 151

2- acetylamino- N- ethyl- 5- bromo- N, 3- dimethyl- benzylamine Melting point: 81-83°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and N-methyl-ethylamine analogously to example 2.

Example 152

2- acetylamino- 5- bromo- N, N- diethyl- 3- methyl- benzylamine The melting point of the hydrochloride: 192.5-194°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and diethylamine analogously to example 2.

Example 153

N-(2-acetylamino-5-bromo-3-methyl-benzyl)-pyrrolidine Melting point: 123-127°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and pyrrolidine analogous to example 2.

Example 154

N-(2-acetylamino-5-bromo-3-methyl-benzyl)- piperidine Melting point: 119-124°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and piperidine analogous to example 2.

Example 155

N-(2-acetylamino-5-bromo-3-methyl-benzyl)-hexamethyleneamine Melting point: 129-132°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide

and hexamethyleneamine analogous to example 2.

Example 156

N-(2-acetylamino-5-bromo-3-methyl-benzyl)-morpholine

Melting point: 105-110°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide

and morpholine analogous to example 2.

Example 157

2- acetylamino- 5- bromo- N- cyclohexyl- N, 3- dimethyl- benzylamine

Melting point: 102-104°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide

and N-methyl-cyclohexylamine analogous to example 2.

Example 158

2- acetylamino- 5- bromo- N, 3- dimethyl- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine

Melting point: 144-146°C. IN

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide

and cis-3-methylamino-cyclohexanol analogous to example 2.

Example 159

2- acetylamino- 5- bromo- N, 3- dimethyl- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine

Melting point: 136.5-138°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide

and trans-4-methylamino-cyclohexanol analogous to example 2.

Example 160

2- acetylamino- N- ethyl- 5- bromo- N- cyclohexyl- 3- methyl- benzylamine Melting point: 115-119°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and N-ethylcyclohexylamine analogously to example 2.

Example 161

2- acetylamino- N- ethyl- 5- bromo- N-( trans- 4- hydroxy- cyclohexyl)- 3- methyl- benzylamine

Melting point: 168-170°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide

and trans-4-ethylamino-cyclohexanol analogous to example 2.

Example 162

2- acetylamino- N- benzy1- 5- bromo- N, 3- dimethyl- benzylamine

Melting point: 97-99°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and N-methylbenzylamine analogously to example 2.

Example 16 3

N-(2-Acetylamino-5-bromo-3-methyl-benzyl)-N'-methyl-piperazine The melting point of the dihydrochloride: 256-257°C (dec.).

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and N-methylpiperazine analogously to example 2.

Example 164

2- amino- N, N, 3- trimethyl-benz y1amine

Melting point of the dihydrochloride: 188-190°C.

Prepared by saponification of 2-acetylamino-N,N,3-trimethyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 165

N-ethyl-2-amino-N,3-dimethyl-benzylamine

Melting point of the dihydrochloride: 196-198°C (dec.).

Prepared by saponification of 2-acetylamino-N-ethyl-N,3-dimethyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 166

2- amino- N, N- dipropyl- 3- methyl- benzylamine

Melting point of the dihydrochloride: 168-173°C (dec.).

Prepared by saponification of 2-acetylamino-N,N-dipropyl-3-methyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 167

2- amino- 5- bromo- N, N, 3- trimethyl- benzylamine Hydrochloride melting point: 218-221°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-N,N,3-trimethyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 168

N- ethyl- 2- amino- 5- bromo- N, 3- dimethyl- benzylamine Melting point of the hydrochloride: 191-193°C (dec.).

Prepared by saponification of 2-acetylamino-N-ethyl-5-bromo-N,3-dimethyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 169

2- amino- 5- bromo- N, N- diethyl- 3- methyl- benzylamine Hydrochlor<i>'s melting point: 177-179°C (dec.).

Prepared from 2-amino-N,N-diethyl-3-methyl-benzylamine hydrochloride and bromine analogous to example 10.

Example 170

N-(2-amino-5-bromo-3-methyl-benzyl)-pyrrolidine

Melting point of the dihydrochloride: 206-210°C (dec.).

Prepared by saponification of N-(2-acetylamino-5-bromo-3-methyl-benzyl)-pyrrolidine in 2n hydrochloric acid analogously to example 13.

Example 171

N-(2-amino-5-bromo-3-methyl-benzyl)- piperidine

Melting point of the dihydrochloride: 176-179°C (dec.).

Prepared by saponification of N-(2-acetylamino-5-bromo-3-methyl-benzyl)-piperidine in 2n hydrochloric acid analogously to example 13.

Example 172

N-( 2- amino- 5- bromo- 3- methyl- benzyl.) - hexamethyleneamine

Melting point of the dihydrochloride: 159-164°C (dec.).

Prepared by saponification of N-(2-acetylamino-5-bromo-3-methyl-benzyl)-hexamethyleneamine in 2n hydrochloric acid analogously to example 13.

Example 173

N-(2-amino-5-bromo-3-methyl-benzyl)-morpholine

Melting point of the dihydrochloride: 159-163°C (dec.).

Prepared by saponification of N-(2-acetylamino-5-bromo-3-methyl-benzyl)-morpholine in 2n hydrochloric acid analogously to example 13.

Example 174

2- amino- 5- bromo- N-( trans- 4- hydroxy- cyclohexyl)- 3- methyl- benzylamine Melting point of the hydrochloride: 225-226°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-N-(trans-4-hydroxy-cyclohexyl)-3-methyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 175

2- amino- 5- bromo- N- cyclohexyl- N, 3- dimethyl- benzylamine Melting point of the hydrochloride: 206.5-207.5°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-N-cyclohexyl-N,3-dimethyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 176

2- amino- 5- bromo- N, 3- dimethyl- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine Melting point: 118-1190C

Prepared by saponification of 2-acetylamino-5-bromo-N,3-dimethyl-N-(cis-3-hydroxy-cyclohexyl)-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 177

2- amino- 5- bromo- N, 3- dimethyl- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine

Melting point: 122-123.5°C.

Prepared by saponification of 2-acetylamino-5-bromo-N,3-dimethyl-N-(trans-4-hydroxy-cyclohexyl)-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 178

N- ethyl- 2- amino- 5- bromo- N- cyclohexyl- 3- methyl- benzylamine The melting point of the dihydrochloride: 183-187°C (dec.).

Prepared by saponification of 2-acetylamino-N-ethyl-5-bromo-N-cyclohexyl-3-methyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 179

N-ethyl-2-amino-5-bromo-N-(trans-4-hydroxy-cyclohexyl)-3-methyl-benzylamine Melting point of the hydrochloride: 156-161°C (dec.).

Prepared by saponification of 2-acetylamino-N-ethyl-5-bromo-N-(trans-4-hydroxy-cyclohexyl)-3-methyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 180

2- amino- N- benzyl- 5- bromo- N, 3- dimethyl- benzylamine

Melting point of the hydrochloride: 214-216°C (dec.).

Prepared by saponification of 2-acetylamino-N-benzyl-5-bromo-N,3-dimethyl-benzylamine in 2n hydrochloric acid analogously to example 13.

Example 181

2- acetylamino- 4- tert. butyl-N-cyclohexyl-N-methyl-benzylamine Melting point of the hydrochloride: 231-234°C.

Prepared from 2-acetylamino-4-tert.butyl-benzyl bromide and N-methyl-cyclohexylamine analogously to example 4.

Example 182

2- acetylamino- 5- bromo- 4- tert. butyl-N,N-dimethyl-benzylamine Melting point: 111-113°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and dimethylamine analogously to example 4.

Example 183

2- acetylamino- 5- bromo- 4- tert. butyl-N,N-diethyl-benzylamine Melting point: 88-91°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and diethylamine analogously to example 4.

Example 184

2- acetylamino- 5- bromo- 4- tert. butyl-N-(hydroxy-tert.butyl)-benzylamine Melting point: 125-127°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl bromide and hydroxy-tert.butylamine analogously to example 4.

Example 185

N-(2-acetylamino-5-bromo-4-tert.butyl-benzyl)-pyrrolidine. Melting point: 103-107°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and pyrrolidine analogous to example 4.

Example 186

N-(2- acetylamino- 5- bromo- 4- tert. butyl- benzyl)- piperidine

Melting point: 132-134°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl bromide and piperidine analogous to example 4.

Example 187

N-(2- acetylamino- 5- bromo- 4- tert. butyl- benzyl)- morpholine

Melting point: 136-139°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and morpholine analogous to example 4.

Example 188

2- acetylamino- 5- bromo- 4- tert. butyl-N-(cis-3-hydroxy-cyclohexyl)-N-methyl-benzylamine

Melting point: 167-172°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and cis-3-methylamino-cyclohexanol analogous to example 4.

Example 189

2- acetylamino- 5- bromo- 4- tert. butyl-N-(trans-4-hydroxy-cyclohexyl)-N-methyl-benzylamine

Melting point: 174-176°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and trans-4-methylamino-cyclohexanol analogous to example 4.

Example 190

2- Acet:ylamino- N- ethyl- 5- bromo- 4- tert. butyl-N-cyclohexyl-benzylamine Melting point: 102-105°C.

Prepared from 2-acetylamino-5-bromo-4-tert-butyl-benzyl-bromide and N-ethyl-cyclohexylamine.

Example 191

N-(2-acetylamino-5-bromo-4-tert.butyl-benzyl)-N'-methyl-piperazine Melting point of the dihydrochloride: from 250°C (dec.).

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and N-methyl-piperazine analogously to example 4.

Example 192

N-(2-acetylamino-5-bromo-4-tert.butyl-benzyl)- camphidine

Melting point: 133-138°C.

Prepared from 2-acetylamino-5-bromo-4-tert.butyl-benzyl-bromide and camphidine analogously to example 4.

Example 19 3

2- amino- 4- tert. butyl- N, N, diethyl- benzylamine -

Melting point of the dihydrochloride: 188-190°C.

Prepared by saponification of 2-acetylamino-4-tert.butyl-N,N-diethylbenzylamine in aqueous-ethanolic hydrochloric acid analogously to example 15.

Example 194

2- amino- 4- tert. butyl-N-cyclohexyl-N-methyl-benzylamine The melting point of the dihydrochloride: 198-199°C.

Prepared by saponification of 2-acetylamino-4-tert.butyl-N-cyclohexyl-N-methyl-benzylamine in 3n hydrochloric acid analogously to example 15.

Example 195

2- amino- 5- bromo- 4- tert. butyl-N,N-dimethyl-benzylamine Melting point of the dihydrochloride: 213-218°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N,N-dimethyl-benzylamine in 3n hydrochloric acid analogously to example 15.

Example 196

2- amino- 5- bromo- 4- tert. butyl-N,N-diethyl-benzylamine

Melting point of the hydrochloride: 198-200°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N,N-diethyl-benzylamine in 3n hydrochloric acid analogously to example 15.

Example 197

2- amino- 5- bromo- 4- tert. butyl-N,N-diallyl-benzylamine

Melting point of the hydrochloride: 176-178°C.

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N,N-diallyl-benzylamine in 3n hydrochloric acid analogously to example 15.

in

Example 198

2- amino- 5- bromo- 4- tert. butyl-N-(hydroxy-tert.butyl)-benzylamine Melting point: 12 3-125°C.

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N-(hydroxy-tert-butyl)-benzylamine in 3n hydrochloric acid analogously to example 15.

Example 199

2- amino- 5- bromo- 4- tert. butyl-N-(1,3-dihydroxy-2-methyl-propyl-2-)-benzylamine

Melting point of the dihydrochloride: 200-205°C (decomp.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N-(1,3-dihydroxy-2-methyl-propyl-2)-benzylamine in 4n hydrochloric acid analogously to example 15.

Example 200

2- amino- 5- bromo- 4- tert. butyl- N-( tris- hydroxymethyl- methyl)- benzylamine The melting point of the dihydrochloride: from 190°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N-(tris-hydroxymethyl-methyl)-benzylamine in hydrochloric acid analogously to example 15.

Example 201

N-(2-amino-5-bromo-4-tert.butyl-benzyl)-pyrrolidine

Melting point of the hydrochloride: from 190°C (decomposition).

Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert.butyl-benzyl)-pyrrolidine in 3n hydrochloric acid analogously to example 15.

Example 202

N-(2-amino-5-bromo-4-tert.butyl-benzyl)-piperidine

Melting point of the dihydrochloride: 188-195°C.

Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert.butyl-benzyl)-piperidine in 3n hydrochloric acid analogously to example 15.

Example 203

N-(2-amino-5-bromo-4-tert.butyl-benzyl)-morpholine

Melting point of the dihydrochloride: 194-198°C (dec.).

Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert-butyl-benzyl)-morpholine in 3n hydrochloric acid analogously to example 15.

Example 204

~ 2- amino- 5- bromo- 4- tert.- butyl- N-{ trans- 4- hydroxy- cyclohexyl)- benzylamine

Melting point of the dihydrochloride: 212-218°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N-(trans-4-hydroxy-cyclohexyl)-benzylamine in 4n hydrochloric acid analogously to example 15.

Example 205

2- amino- 5- bromo- 4- tert. butyl-N-(cis-3-hydroxy-cyclohexyl)-N-methyl-benzylamine

Melting point of the dihydrochloride: 205-208°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N-(cis-3-hydroxy-cyclohexyl)-N-methyl-benzylamine in 4n hydrochloric acid analogously to example 15.

Example 206

2- amino- 5- bromo- 4- tert. butyl-N-(trans-4-hydroxy-cyclohexyl)-N-methyl-benzylamine

Melting point of the hydrochloride: 208-210°C (dec.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert-butyl-N-(trans-4-hydroxy-cyclohexyl)-M-methyl-benzylamine in 3n hydrochloric acid analogous to example 15.

Example 207

N-ethyl 1- 2- amino- 5- bromo- 4- tert. butyl-N-cyclohexyl-benzylamine Melting point of the hydrochloride: 191-194°C (dec.).

Prepared by saponification of 2-acetylamino-N-ethyl-5-bromo-4-tert.butyl-N-cyclohexyl-benzylamine in aqueous-ethanolic hydrochloric acid analogously to example 15.

Example 208

N-(2-amino-5-bromo-4-tert.butyl-benzyl)-N'-methyl-piperazine Trihydrochloride melting point: 170-180°C (decomposition).

Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert.butyl-benzyl)-N'-methyl-piperazine in 3n hydrochloric acid analogously to example Example 209

N-(2- amino- 5- bromo- 4- tert. butyl- benzyl)- camphidine

Melting point of the dihydrochloride: 198-205°C (dec.).

Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert-butyl-benzyl)-camphidine in 3n hydrochloric acid analogously to example 15.

Example 210

4- amino- 3- tert. butyl-N,N-diethyl-benzylamine

Melting point of the dihydrochloride: 183-185°C (dec.).

Prepared by saponification of 4-acetylamino-3-tert.butyl-N,N-diethyl-benzylamine in 3n hydrochloric acid analogously to example 17.

Example 211

4- amino- 5- bromo- 3- tert. butyl-N,N-diethyl-benzylamine The melting point of the dihydrochloride: 201-204°C (dec.).

Prepared from 4-amino-3-tert.butyl-N,N-diethyl-benzylamine dihydrochloride and bromine analogously to example 10.

Example 212

4- amino- 5- bromo- 3- tert. butyl-N-cyclohexyl-N-methyl-benzylamine Melting point of the hydrochloride: 198-201°C (dec.).

Prepared from 4-amino-3-tert.butyl-N-cyclohexyl-N-methyl-benzylamine dihydrochloride and bromine analogously to example 10.

Example 213

5- acetyl- 2- acetylamino- N, N- diethyl- benzylamine Melting point: 102-103°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and diethylamine analogously to example 8.

Example 214

5- acetyl- 2- acetylamino- N, N- dipropyl- benzylamine Melting point: 80-82°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and dipropylamine analogous to example 8.

Example 215

5- acetyl- 2- acetylamino- N, N- dibutyl- benzylamine Melting point: 40-42°C

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and dibutylamine analogously to example 8.

Example 216

N-(5-acetyl-2-acetylamino-benzyl)-pyrrolidine

Melting point: 88-90°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and pyrrolidine analogous to example 8.

Example 217

IS - (5-acetyl-2-acetylamino-benzyl)-piperidine

Melting point for the hydrochloride: 210-212°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and

..piperidine analogous to example 8.

Example 218

N~( 5- acetyl- 2- acetylamino- benzyl)- hexamethyleneamine Melting point: 112-114°C..

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and hexamethyleneamine analogously to example 8.

Example 219

N-(5-acetyl-2-acetylamino-benzyl)-morpholine

Melting point: 100-102°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and morpholine analogous to example 8.

Example 220

5- acety1- 2- acetylamino- N- cyclohexyl- N- methyl- benzylamine The melting point of the hydrochloride: 210-211°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and N-methylcyclohexylamine analogously to example 8.

Example 221

5- acetyl- 2- acetylamino- N- ethyl- N- cyclohexyl- benzylamine Melting point: 98-100°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and N-ethyl-cyclohexylamine analogous to example 8.

Example 222

5- acetyl- 2- acetylamino- N- cyclohexyl- N- isopropyl- benzylamine Melting point: 108-110°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and N-isopropylcyclohexylamine analogously to example 8.

Example 223

N-(5- acetyl- 2- acetylamino- benzyl)- N'- methyl-piperazine The melting point of the hydrochloride: from 275°C (decomposition).

Prepared from 5-acetyl-2-acetylamino-benzyl bromide and N-methyl-piperazine analogously to example 8.

Example 224

5- acetyl- 2- amino- N, N- diethyl- benzylamine

Melting point of the hydrochloride: 218-221°C.

Prepared by saponification of 5-acetyl-2-acetylamino-N,N-diethyl-benzylamine in aqueous-ethanolic caustic soda analogous to example lb.

Example 225

5- acetyl- 2- amino- N, N- dipropyl- benzylamine

Melting point of the hydrochloride: 171-173°C.

Prepared by saponification of 5-acetyl-2-acetylamino-N,N-dipropyl-benzylamine in aqueous-ethanolic caustic soda analogous example

Example 2 26

5- acety1- 2- amino- N, N- dibutyl- benzylamine

Melting point of the hydrochloride: 110-120°C.

Prepared by saponification of 5-acetyl-2-acetylamino-N,N-dibutyl-benzylamine in 4n hydrochloric acid analogously to example 16.

Example 22 7

N-(5-acetyl-2-amino-benzyl)-pyrrolidine

Melting point of the hydrochloride: 203-205°C.

Prepared by saponification of N-(5-acetyl-2-acetylamino-benzyl)-pyrrolidine in aqueous-ethanolic caustic soda analogous to example 10.

Example 228

N-(5-acetyl-2-amino-benzyl)-piperidine

Melting point of the hydrochloride: 220-222°C.

Prepared by saponification of N-(5-acetyl-2-acetylamino-benzyl)-piperidine in aqueous-ethanolic caustic soda analogous to example 18.

Example 229

N-(5-acetyl-2-amino-benzyl)-hexamethyleneamine

Melting point of the hydrochloride: 205-207°C (dec.).

Prepared by saponification of N-(5-acetyl-2-acetylamino-benzyl)-hexamethyleneamine in aqueous-ethanolic caustic soda analogous to example 18.

Example 230

N-(5-acetyl-2-amino-benzyl)-morpholine

Melting point of the hydrochloride: 218-220°C (dec.).

Prepared by saponification of N-(5-acetyl-2-acetylamino-benzyl)-morpholine in aqueous-ethanolic caustic soda analogous to example 18.

Example 2 31 5-acetyl-N-ethyl-2-amino-N-cyclohexyl-benzylamine

Melting point: 100-102°C.

Prepared by saponification of 5-acetyl-2-acetylamino-N-ethyl-N-cyclohexyl-benzylamine in aqueous-ethanolic caustic soda analogously

example 18.

Example 232

N-(5-acetyl-2-amino-benzyl)-N'-methyl-piperazine

Melting point: 135-138°C.

Prepared by saponification of N-(5-acetyl-2-acetylamino-benzyl)-N'-methyl-piperazine in aqueous-ethanolic caustic soda analogous to example 18.

Example 233

5- acetyl- 2- amino- 3- bromo- N, N- diety1- benzylamine Melting point of the hydrochloride: 208-212°C.

Prepared from 5-acetyl-2-amino-N,N-diethyl-benzylamine hydrochloride and bromine analogous to example 11.

Example 2 34

5- acety1- 2- amino- 3- bromo- N, N- dipropyl- benzylamine The melting point of the hydrochloride: 136-140°C.

Prepared from 5-acetyl-2-amino-N,N-dipropyl-benzylamine hydrochloride and bromine analogous to example 11.

Example 2 35

5- acetyl- 2- amino- 3- bromo- N, N- dibutyl- benzylamine Melting point of the hydrochloride: 112-115°C.

Prepared from 5-acetyl-2-amino-N,N-dibutyl-benzylamine hydrochloride and bromine analogous to example 11.

Example 236

N-(5-acetyl-2-amino-3-bromo-benzyl)-pyrrolidine The melting point of the hydrochloride: 165-167°C.

Prepared from N-(5-acetyl-2-amino-benzyl)-pyrrolidine hydrochloride and bromine analogously to Example 11.

Example 2 37

N-(5-acetyl-2-amino-3-bromo-benzyl)- piperidine

Melting point: 108-110°C.

Prepared from N-(5-acetyl-2-amino-benzyl)-piperidine hydrochloride and bromine analogously to example 11.

Example 238

N-(5-acetyl-2-amino-3-bromo-benzyl)- hexamethyleneamine The melting point of the hydrochloride: 203-206°C.

Prepared from N-(5-acetyl-2-amino-benzyl)-hexamethyleneamine hydrochloride and bromine analogously to example 8.

Example 239

N-(5-acetyl-2-amino-3-bromo-benzyl)-morpholine Hydrochloride melting point: 235-239°C (dec.).

Prepared from N-(5-acetyl-2-amino-benzyl)-morpholine hydrochloride and bromine analogously to example 11.

Example 240

5- acetyl- 2- amino- 3- bromo- N- cyclohexyl- N- methyl- benzylamine

Melting point of the hydrochloride: 229-231°C.

Prepared from 5-acetyl-2-amino-N-cyclohexyl-N-methyl-benzylamine dihydrochloride and bromine analogously to example 11.

Example 2 41

5- acety1- N- ethyl- 2- amino- 3- bromo- N- cyclohexyl- benzylamine. Melting point: 111-113°C.

Prepared from 5-acetyl-N-ethyl-2-amino-N-cyclohexyl-benzylamine and bromine analogous to example 11.

Example 2 42

N-(5- acetyl- 2- amino- 3- bromo- benzyl)- N'- methyl- piperazine

Melting point: 99-104°C.

Prepared from N-(5-acetyl-2-amino-benzyl)-N'-methyl-piperazine and bromine analogously to Example 11.

Example 2 43

2- amino- 3- bromo- N, N- dimethyl- 5-( 1- hydroxy- ethyl)- benzylamine Melting point: 69-72°C.

Prepared by reduction of 5-acetyl-2-amino-3-bromo-N,N-dimethyl-benzylamine with sodium borohydride analogously to example 19.

Example 2 44

2- amino- 3- bromo- N, N- diethyl- 5-( 1- hydroxy- ethyl)- benzylamine Melting point: 62-65°C.

Prepared by reduction of 5-acetyl-2-amino-3-bromo-N,N-diethyl-benzylamine with sodium borohydride analogously to example 19.

Example 2 45

2- amino- 3- bromo- N, N- dipropyl- 5-( 1- hydroxy- ethyl)- benzylamine Melting point: 52-54°C.

Prepared by reduction of 5-acetyl-2-amino-3-bromo-N,N-dipropyl-benzylamine with sodium borohydride analogously to example 19.

Example 2 46

2- amino- 3- bromo- N, N- dibutyl- 5-( 1- hydroxy- ethyl)- benzylamine Melting point: 48-51°C.

Prepared by reduction of 5-acetyl-2-amino-3-bromo-N,N-dibutyl-benzylamine with sodium borohydride analogously to example 19.

Example 2 47

N-[2-amino-3-bromo-5-(1-hydroxy-ethyl)-benzyl]-pyrrolidine Melting point: 98-102°C.

Prepared by reduction of N-(5-acetyl-2-amino-3-bromo-benzyl)-pyrrolidine with sodium borohydride, analogous to example 19.

Example 2 48

N- ethyl- 2- amino- 3- bromo- N- cyclohexyl- 5-( 1- hydroxy- ethyl)- benzylamine Melting point: 117-121°C.

Prepared by reduction of 5-acetyl-N-ethyl-2-amino-3-bromo-N-cyclohexyl-benzylamine with sodium borohydride analogous to example 19.

Example 249

N-[2-amino-3-bromo-5-(1-hydroxy-ethyl)-benzyl]-N'-methyl- piperazine Melting point: 134-136°C.

Prepared by reduction of N-(5-acetyl-2-amino-3-bromo-benzyl)-N'-methyl-piperazine with sodium borohydride analogously to example 19.

Example 250

2-amino-N-isopropyl-3-trifluoromethyl-benzylamine

Melting point of the hydrochloride: 188-189°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and isopropylamine analogously to example 1.

Example 251

2- amino- N, N- diety1- 3- trifluoromethyl- benzylamine

Melting point of the hydrochloride: 194-196°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and diethylamine analogously to example 1.

Example 252

N-(2-amino-3-trifluoromethyl-benzyl)-hexamethyleneamine

Melting point of the hydrochloride: 208-209°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and hexamethyleneamine analogously to example 1.

Example 253

N-ethyl1- 2- amino- N- cyclohexyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 189-191°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and N-ethyl-cyclohexylamine analogously to example 1.

Example 254

2- amino- N- methyl- N-( morpholino- carbonyl- methyl)- 3- trifluoromethyl- benzylam. Melting point of the hydrochloride: 200-203°C (dec.).

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and sarcosine morpholide analogously to example 1.

Example 255

2- amino- 5- bromo- N-o isopropyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 206-208°C.

Prepared from 2-amino-N-isopropyl-3-trifluoromethyl-benzylamine and bromine analogously to example 10.

Example 256

2- amino- 5- bromo- N, N- diethyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 198-200°C.

Prepared from 2-amino-N,N-diethyl-3-trifluoromethyl-benzylamine and bromine analogous to example 10.

Example 257

N-(2-amino-5-bromo-3-trifluoromethyl-benzyl)- hexamethyleneamine Melting point of the hydrochloride: 223-225°C.

Prepared from N-(2-amino-3-trifluoromethyl-benzyl)-hexamethyleneamine and bromine analogously to example 10.

Example 258

N- ethyl- 2- amino- 5- bromo- N- cyclohexyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 204-207°C.

Prepared from N-ethyl-2-amino-N-cyclohexyl-3-trifluoromethyl-benzylamine and bromine analogous to example 10.

Example 259

2- amino- 5- bromo- N- methyl- N-( morpholino- carbonyl- methyl)- 3- trifluoromethyl- benzylamine

Melting point of the hydrochloride: 211-215°C (dec.).

Prepared from 2-amino-N-methyl-N-(morpholino-carbonyl-methyl)-3-trifluoromethyl-benzylamine and bromine analogous to example 10.

Example 260

2- amino- 5- chloro- N- isopropyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 197-200°C.

Prepared from 2-amineb-N-isopropyl-3-trifluoromethyl-benzylamine and phenyliododichloride analogously to example 12.

Example 261

Melting point of the hydrochloride: 197-198°C.

Prepared from 2-amino-N,N-diethyl-3-trifluoromethyl-benzylamine and phenyliododichloride analogous to example 12.

Example 262

N-(2-amino-5-chloro-3-trifluoromethyl-benzyl)- hexamethyleneamine The melting point of the hydrochloride: 128-130°C.

Prepared from N-(2-amino-3-trifluoromethyl-benzyl)-hexamethyleneamine and phenyliododichloride analogously to example 12.

Example 26 3

N- ethyl- 2- amino- 5- chloro- N- cyclohexyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 202-205°C.

Prepared from N-ethyl-2-amino-N-cyclohexyl-3-trifluoromethyl-benzylamine and phenyliododichloride analogously to example 12.

Example 264

2- amino- 5- chloro- N- methyl- N-( morpholino- carbonyl- methyl)- 3- trifluoromethyl- benzylamine

Melting point of the hydrochloride: 200-207°C (decomp.).

Prepared from 2-amino-N-methyl-N-(morpholino-carbonyl-methyl)-3-trifluoromethyl-benzylamine and phenyliododichloride analogous to example 12.

Example 265

N-(2-amino-3-bromo-5-fluoro-benzyl)-pyrrolidine

Melting point of the dihydrochloride: 173-175°C (dec.).

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and pyrrolidine analogous to example 1.

Example 266

2- amino- 3- bromo- 5- fluoro- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine. Melting point of the hydrochloride: 237-239°C (dec.).

Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and trans-4-hydroxy-cyclohexylamine analogous to example 1.

Example 267-2-benzoylamino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine Melting point of the hydrochloride: 220-222°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine and benzoyl chloride in benzene solution analogous to example 22.

Example 268

3- bromo- 5- carbetoxy- 2- ( 4- chloro- benzoylamino)- N, N- diethyl- benzylamine Melting point of the hydrochloride: 187-193°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine and 4-chloro-benzoyl chloride in benzene solution analogous to example 22

Example 269

2- acetamino- 5- carbomethoxy- N, N- diethyl- benzylamine

3.4 g of 2-acetamino-5-carbomethoxy-benzyl bromide are dissolved in

125 ml of chloroform and allowed to stand for 15 minutes after adding 35 ml of diethylamine. The mixture is evaporated to dryness in vacuo, the residue is taken up in chloroform, the chloroform solution is shaken with dilute hydrochloric acid, the

aqueous phase is made alkaline with ammonia and it is shaken

new with chloroform. This chloroform extract is dried over sodium

sulfate and evaporated in vacuo. The residue is 2-acetamino-5-carbomethoxy-N,N-diethyl-benzylamine (melting point: 77-80°C) and is transferred with

methanolic hydrochloric acid in the hydrochloride with melting point 213-214°C.

Example 270

2- amino- 3- bromo- 5- carbomethoxy- N, N- diethyl- benzylamine

1.6 g of 2-amino-5-carbomethoxy-N,N-diethyl-benzylamine is dissolved in

2 7 ml acetic acid and 3 ml water and a solution of 1.1 g bromine in 2 ml acetic acid is added dropwise at room temperature and stirring. After an hour's rest, pour on ice, make alkaline with ammonia and extract with chloroform. The chloroform solution is dried over sodium sulfate and evaporated to dryness in vacuo. The residue is dissolved in acetone and 2-amino-3-bromo-5-carbomethoxy-N,N-diethylbenzylamine hydrochloride with melting

point 180-181°C is precipitated with ethereal hydrochloric acid.

Example 271

2-amino-5-carbomethoxy-N,N-diethyl-benzylamine

2.5 g 2-acetamino-5-carbomethoxy-N,N-diethyl-benzylamine

boil for 30 minutes with 50 ml of methanol and 15 ml of concentrated hydrochloric acid. The mixture is poured onto ice, made alkaline with ammonia, shaken out with chloroform, the chloroform solution is dried over sodium sulfate,

is evaporated in vacuo and 2-amino-5-carbomethoxy-N,N-diethyl-benzylamine-hydrogen fumarate is obtained from the residue by dissolution in methanol and addition of fumaric acid in ether.

Melting point: 177-179°C.

Example 272

N-ethyl-2- amino- 3- bromo- 5- carboxy- benzylamine

2.7 g of N-ethyl-2-amino-3-bromo-5-carbomethoxy-benzylamine

boil for 35 minutes with 65 ml of 6N hydrochloric acid. Upon cooling to -15°C, N-ethyl-2-amino-3-bromo-5-carboxy-benzylamine hydrochloride crystallizes out. It is recrystallized from ethanol/ether.

Melting point of the hydrochloride: 261°C (dec.).

Example 273

2- amino- 5- bromo- N, N- dimethyl- 3- fluoro- benzylamine

Dissolve 5.5 g of 2-amino-5-bromo-3-fluoro-benzyl alcohol in 150 ml of chloroform. While stirring and cooling with ice, 7.13 g are added dropwise

(4.35 ml) of thionyl chloride, whereby a yellow precipitate is precipitated. The suspension is allowed to stand overnight at room temperature and it is evaporated

then to dryness at room temperature in a rotary evaporator. The crude benzyl chloride thus obtained is suspended in 150 ml of chloroform. While stirring and cooling with ice, 20 ml of dimethylamine is added to this, whereby a clear solution is obtained. It is allowed to stand for 30 minutes under ice cooling and then extracted twice with saturated potassium carbonate solution. The chloroform phase is washed with water, dried over sodium sulphate and evaporated to dryness in vacuo. The residue is taken up in absolute ethanol and acidified with ethereal hydrochloric acid to pH 3. The precipitated hydrochloride is suctioned off and dissolved in absolute ethanol. After adding activated charcoal, the solution is heated to boiling. After filtering off the activated carbon and adding ether, colorless crystals with a melting point of 263-265°C (dec.) are obtained.

Example 274

2- amino- 5- bromo- N- cyclohexyl- 3- fluoro- N- methyl- benzylamine Melting point of the hydrochloride: 226-228°C (dec.).

Prepared from 2-amino-5-bromo-3-fluoro-benzyl alcohol, thionyl chloride and N-methyl-cyclohexylamine analogous to example 2 73.

Example 2 75

2-amino-5-bromo-N-(trans-4-hydroxy-cyclohexyl)-3-fluoro-benzylamine Melting point of the hydrochloride: 2 31-233°C.

Prepared from 2-amino-5-bromo-3-fluoro-benzyl alcohol, thionyl chloride and trans-4-hydroxy-cyclohexylamine analogous to Example 273.

Example 276

N- ethyl1- 2- amino- 5- bromo- N- cyclohexyl- 3- fluoro- benzylamine Melting point of the hydrochloride: 193-195°C.

Prepared from 2-amino-5-bromo-3-fluoro-benzylamine, thionyl chloride and N-ethyl-cyclohexylamine analogous to Example 273.

Example 277

N-(2-amino-5-carboxy-benzyl)-pyrrolidine

Melting point of the hydrochloride: 193-194°C (dec.).

Prepared from N-(2-amino-5-carbethoxy-benzyl)-pyrrolidine

and 6n hydrochloric acid analogous to example 2 72.

Example 278

N-(2-amino-3-bromo-5-carboxy-benzyl)-pyrrolidine

Melting point of the hydrochloride: 267°C (dec.).

Prepared from N-(2-amino-3-bromo-5-carbethoxy-benzyl)-pyrrolidine and 6n hydrochloric acid analogously to Example 272.

in

Example 279

2- amino- 5- carboxy- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 224°C (dec.).

Prepared from 2-amino-5-carbethoxy-N-(trans-4-hydroxy-cyclohexyl)-benzylamine and 6n hydrochloric acid analogously to Example 272.

Example 280

2- amino- 3- bromo- 5- carboxy- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 279°C (dec.).

Prepared from 2-amino-3-bromo-5-carbethoxy-N-(trans-4-hydroxy-cyclohexyl)-benzylamine and 6n hydrochloric acid analogously to Example 272.

Example 281

N-(2-amino-5-carboxy-benzyl)-morpholine

Melting point of the hydrochloride: 222°C (dec.).

Prepared from N-(2-amino-5-carbethoxy-benzyl)-morpholine and 6n hydrochloric acid analogous to Example 272.

Example 282

N-(2-amino-3-bromo-5-carboxy-benzyl)-morpholine

Melting point of the hydrochloride: 286°C (dec.).

Prepared from N-(2-amino-3-bromo-5-carbethoxy-benzyl)-morpholine and 6n hydrochloric acid analogous to example 2 72.

Example 2 83

N-(2-amino-5-carboxy-benzyl)-hexamethyleneamine

Melting point of the dihydrochloride: from 121°C (dec.).

Prepared from N-(2-amino-5-carbethoxy-benzyl)-hexamethyleneamine and 6n hydrochloric acid analogously to Example 272.

Example 2 84

N-(2- amino- 3- bromo- 5- carboxy- benzyl)- hexamethylene amine Hydrochloride melting point: from 224°C (dec.).

Prepared from N-(2-amino-3-bromo-5-carbethoxy-benzyl)-hexamethyleneamine and 6n hydrochloric acid analogously to Example 272.

Example 285

2- amino- 5- carboxy- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine Dihydrochloride melting point: 162°C (dec.).

Prepared from 2-amino-5-carbethoxy-N-(cis-hydroxy-cyclohexyl)-benzylamine and 6n hydrochloric acid analogously to Example 272.

Example 286

2- amino- 3- bromo- 5- carboxy- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine

Melting point of the hydrochloride: 119°C (dec.).

Prepared from 2-amino-3-bromo-5-carbethoxy-N-(cis-hydroxy-cyclohexyl)-benzylamine and 6n hydrochloric acid analogously to Example 272.

Example 287

2- acetamino- 5- bromo- N, N- dimethyl- 3- dimethylamino- methyl- benzylamine

12 g of 4-bromo-2,6-dimethylacetanilide are dissolved in 1.9 l of tetrachloromethane and heated to boiling. The solution is irradiated with UV light and 15.8 g of bromine are added dropwise over the course of 50 minutes. After cooling to room temperature, 60 ml of dimethylamine is added and the mixture is allowed to stand overnight. It is shaken twice with water, dried over sodium sulphate and evaporated to dryness in vacuo. The residue is dissolved in ethanol and the solution is acidified with ethanolic hydrochloric acid. 2-acetamino-5-bromo-N,N-dimethyl-3-dimethylamino-methyl-benzylamine dihydrochloride with melting point 291°C (dec.) is crystallized.

Example 288

4-bromo-2,6-bis-(pyrrolidino-methyl)-acetanilide

Melting point of the dihydrochloride: 319°C (dec.).

Prepared from 4-bromo-2,6-dimethylacetanilide, bromine and pyrrolidine analogous to Example 287.

Example 2 89

4-bromo-2,6-bis-(piperidino-methyl)-acetanilide

Melting point of the dihydrochloride: 308-312°C (dec.).

Prepared from 4-bromo-2,6-dimethylacetanilide, bromine and piperidine analogous to Example 287.

Example 290

4-bromo-2,6-bis-(morpholino-methyl)-acetanilide

Melting point of the dihydrochloride: 283-284°c (dec.).

Prepared from 4-bromo-2,6-dimethylacetanilide, bromine and morpholine analogous to Example 287.

Example 291

2- amino- 5- bromo- 3- dimethylaminomethyl- N, N- dimethyl- benzylamine Melting point of the dihydrochloride: 284-287°C (dec.).

Prepared from 2-acetamine.o-5-bromo-3-dimethylaminomethyl-N,N-dimethyl-benzylamine and hydrochloric acid analogous to example 2 71.

Example 292

4-bromo-2,6-bis-(piperidino-methyl)-aniline

Melting point of the dihydrochloride: 283-286°C (dec.).

in

Prepared from 4-bromo-2,6-bis-(piperidino-methyl)-

acetanilide and hydrochloric acid analogous to example 271.

Example 293

4-bromo-2/6-bis-(morpholino-methyl)-aniline

The melting point of the dihydrochloride 251-257°C (dec.).

Prepared from 4-bromo-2,6-bis-(morpholino-methyl)-acetanilide and hydrochloric acid analogously to Example 271.

Example 2 94

5- acetyl- 2- amino- 3- bromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 214-216°C (dec.).

Prepared from 5-acetyl-2-amino-3-bromo-benzyl bromide and trans-4-hydroxy-cyclohexylamine analogous to Example 269.

Example 295

5- acetyl- 2- amino- 3- chloro- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 192-194°C (dec.).

Prepared from 4-acetamino-2-amino-3-chloro-benzyl bromide and trans-4-hydroxy-cyclohexylamine analogous to Example 269.

Example 296 2-amino-5-bromo-N-[1,3-dihydroxy-2-methyl-propyl-(2)]-3-trifluoromethyl-benzylamine

Melting point of the hydrochloride: 226-228°C (dec.).

Prepared from 2-amino-N-[1,3-dihydroxy-2-methyl-propyl-(2)]-3-trifluoromethyl-benzylamine and bromine analogous to example 270.

Example 297

2- amino- N-[ 1, 3- dihydroxy- 2- methyl- propyl-( 2)]- 3- trifluoromethyl- benzylamine

Melting point: 110-112°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and 2-amino-2-methyl-1,3-propanediol analogously to Example 269.

Example 298

2- amino- 5- bromo- N-( cis- 3- hydroxy- cyclohexyl)- 3- trifluoromethyl- benzylamine

Melting point of the hydrochloride: from 70°C (splitting).

Prepared from 2-amino-N-(cis-3-hydroxy-cyclohexyl)-3-trifluoromethyl-benzylamine and bromine analogously to Example 270.

Example 299

2- amino- N-( cis- 3- hydroxy- cyclohexyl)- 3- trifluoromethyl- benzylamine

Melting point of the hydrochloride: 196-200°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and cis-3-hydroxy-cyclohexylamine analogously to example 26 9.

Example 300

2- amino- 5- bromo- N-( hydroxy- tert. butyl)- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 226-228°C (dec.).

Prepared from 2-amino-N-(hydroxy-tert.butyl)-3-trifluoromethyl-benzylamine and bromine analogously to Example 270.

Example 301

2- amino- 5- bromo- N-( trans- 4- hydroxy- cyclohexyl)- 3- trifluoromethyl- benzylamine

Melting point of the hydrochloride: 233-236°C (dec.).

Prepared from 2-amino-N-(trans-4-hydroxy-cyclohexyl)-3-trifluoromethyl-benzylamine and bromine analogously to Example 270.

Example 302

2- amino- N-( trans- 4- hydroxy- cyclohexyl)- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 228-230°C (dec.).

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and trans-4-hydroxy-cyclohexylamine analogously to example 26 9.

in Example 303. 2-amino-N-(hydroxy-tert.butyl)-3-trifluoromethyl-benzylamine Melting point: 110-112°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and hydroxy-tert-butylamine analogously to example 269.

Example 304

2- amino- 5- chloro- N, N- dimethyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 210-212°C (dec.).

Prepared from 2-amino-3-trifluoromethyl-benzylamine and phenyliododichloride analogously to Example 270.

Example 305

2- amino- 5- bromo- N, N- dimethyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 184-185°C.

Prepared from 2-amino-N,N-dimethyl-3-trifluoromethyl-benzylamir and bromine analogous to Example 270.

Example 306

N- ethyl- 2- amino- 3- carbethoxy- benzylamine

3.8 g of N-ethyl-2-amino-N-benzyl-5-carbethoxy-benzylamine are hydrated in 50 ml of methanol and 1 ml of concentrated hydrochloric acid at room

temperature and at 5 ato hydrogen pressure in the presence of palladium on charcoal. The catalyst is filtered off and the filtrate is evaporated to dryness in a vacuum. The residue is recrystallized from ethanol with the addition of ether. N-ethyl-2-amino-5-carbethoxy-benzylamine hydrochloride with melting point 173-176°C. (splitn.) is obtained.

Example 307

3- bromo- 2- butyrylamino- 5- carbethoxy- N, N- diethyl- benzylamine

3 g of 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine are dissolved in 30 ml of benzene and heated with 3 ml of butyric acid chloride for 30 minutes at 50°C. The solution is evaporated to dryness in vacuo and the residue is purified by chromatography on silica gel (eluent: benzene: ethyl acetate = 6:1). 3-bromo-2-butyryl-amino-5-carbethoxy-N,N-diethyl-benzylamine is obtained, which is transferred to the hydrochloride with a melting point of 134°C.

Example 308

N- ethyl- 2- amino- N- benzyl- 5- carbethoxy- benzylamine

Melting point of the hydrochloride: from 61°C (splitting).

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and N-ethyl-benzylamine analogous to example 269 and the reactions of the crude 2-acetamino-N-ethyl-N-benzyl-5-carbethoxy-benzylamine thus obtained with ethanol/hydrochloric acid analogous to example 271.

Example 309

N-(2-acetamino-5-carbethoxy-benzyl)-pyrrolidine

Oil, chromatographically uniform.

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and pyrrolidine analogously to example 26 9.

Example 310

N-(2-amino-5-carbethoxy-benzyl)-pyrrolidine

Melting point of the dihydrochloride: 146-14 9°C

Prepared from N-(2-acetamino-5-carbethoxy-benzyl)-pyrrolidine and ethanol/hydrochloric acid analogously to example 2 71.

Example 311

N-(2-amino-3-bromo-5-carbethoxy-benzyl)-pyrrolidine

Melting point of the hydrochloride: 204-205°C.

Prepared from N-(2-amino-5-carbethoxy-benzyl)-pyrrolidine and bromine analogous to example 2 70.

Example 312

2- amino- 5- carbethoxy- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 237°C (decomposition).

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and trans-4-hydroxy-cyclohexylamine analogous to example 26 9 and reaction of the thus obtained 2-acetamino-5-carbethoxy-N-(trans-4-hydroxy-cyclohexyl)-benzylamine with ethanol/hydrochloric acid analogous to example 2 71.

Example 313

2- amino- 3- bromo- 5- carbethoxy- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine

Melting point of the hydrochloride: 137°C (dec.).

Prepared from 2-amino-5-carbethoxy-N-(trans-4-hydroxy-cyclohexyl)-benzylamine and bromine analogous to Example 270.

Example 314

2- acetamino- 3- bromo- 5- carbethoxy- N- cyclohexyl- N- methyl 1- benzylamine Melting point of the hydrochloride: 220-223°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine and acetyl chloride analogously to Example 307.

Example 315

N-(2-amino-5-carbethoxy-benzyl)-morpholine

Melting point of the hydrochloride: 205°C (dec.).

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and morpholine analogous to example 269 and reaction of the thus obtained N-(2-acetamino-5-carbethoxy-benzyl)-morpholine with ethanol/hydrochloric acid analogous to example 271.

Example 316

N-(2-amino-3-bromo-5-carbethoxy-benzyl)-morpholine

Melting point of the hydrochloride: 221°C (dec.).

Prepared from N-(2-amino-5-carbethoxy-benzyl)-morpholine and bromine analogous to Example 270.

Example 317

N-(2-amino-5-carbethoxy-benzyl)-hexamethyleneamine

Melting point of the hydrochloride: 168-169°C.

Prepared from N-(2-acetamino-5-carbethoxy-benzyl)-hexamethyleneamine and ethanol/hydrochloric acid analogous to example 271.

Example 318

N-(2-amino-3-bromo-5-carbethoxy-benzyl)- hexamethyleneamine

Melting point of the hydrochloride: 219-221°C.

Prepared from N-(2-amino-5-carbethoxy-benzyl)-hexamethyleneamine and bromine analogous to Example 2 70.

Example 319

2- acetamino- N- benzyl- 5- carbethoxy- N- tert. butyl-benzylamine Melting point of the hydrochloride: 208°C (dec.).

Prepared from 2-acetamino-5-carbethoxy-benzylbromide and N-tert-butyl-benzylamine analogous to example 269.

Example 320

2- amino- 5- carbethoxy- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 201-203°C.

Prepared from 2-acetamino-5-carbethoxy-benzyl bromide and cis-3-hydroxy-cyclohexylamine analogously to example 2 69 and reaction of the thus obtained 2-acetamino-5-carbethoxy-N-(cis-hydroxy-cyclohexyl)-benzylamine with ethanol /hydrochloric acid analogous to example 271.

Example 321

2- amino- 3- bromo- 5- carbethoxy- N-( cis- 3- hydroxy- cyclohexyl)- benzylamine Melting point of the hydrochloride: 103°C (dec.).

Prepared from 2-amino-5-carbethoxy-N-(cis-3-hydroxy-cyclohexyl)-benzylamine and bromine analogous to Example 270.

Example 322

2- amino- 5- carbomethoxy- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Fumarate's melting point: 221°C (dec.).

Prepared from 2-acetamino-5-carbomethoxy-benzyl bromide and trans-4-hydroxy-cyclohexylamine analogous to example 269 and reaction of the thus obtained 2-acetamino-5-carbomethoxy-N-(trans-4-hydroxy-cyclohexyl)-benzylamine with methanol/hydrochloric acid analogous to example 271.

Example 323

2- amino- N, N- diethyl- 5- isopropoxy- carbonyl- benzylamine

Melting point of hydrogen fumarate: 158°C.

Prepared from 2-acetamino-5-isopropoxy-carbonyl-benzyl-bromide and diethylamine analogous to example 269 and reaction of the thus obtained 2-acetamino-N,N-diethyl-5-isopropoxy-carbonyl-benzylamine with isopropanol/hydrochloric acid analogous to example 271 .

Example 324

2-acetamino-N-benzyl-5,N-dimethyl-benzylamine

The substance is an oil, structural evidence by UV, NMR and IR spectra. Prepared from 2-acetamino-5-methyl-benzyl bromide and N-methyl-benzylamine analogous to example 269.

Example 325

N- ety1- 2- amino- 3- bromo- 5- carbethoxy- benzylamine

Melting point: 199-201°C.

Prepared from N-ethyl-2-amino-5-carbethoxy-benzylamine and bromine analogous to example 270.

Example 326

4-bromo-2,6-bis-(pyrrolidino-methyl)-aniline

Melting point of the dihydrochloride: 274-276°C (dec.).

Prepared from 4-bromo-2,6-bis-(pyrrolidino-methyl)-acetanilide and hydrochloric acid analogously to Example 271.

Example 32 7

2- amino- 3- bromo- N-( trans- 4- hydroxy- cyclohexyl)- 5- methoxy- benzylamine

Amorphous, structural evidence by IR, UV and NMR spectra.

Prepared from 2-amino-3-bromo-5-methoxy-benzyl alcohol, thionyl chloride and trans-4-hydroxy-cyclohexylamine analogous to Example 273.

Example 32 8

N- ethyl- 2- amino- 3- bromo- N- cyclohexyl- 5- methyl- benzylamine

4.4 g of 2-amino-3-bromo-5-methyl-benzyl alcohol are heated with 1.5 g of propionic acid and 3 g of N-ethyl-cyclohexylamine for 5 hours at 165°C. It is evaporated to dryness in a vacuum, the residue is taken up in ether, shaken twice with water, dried, evaporated to dryness in a vacuum and the residue is purified by chromatography on silica gel (eluent: chloroform-ethyl acetate = 6:1). The eluate is evaporated, taken up in isopropanol and the hydrochloride with a melting point of 184-186°C is brought to crystallization with hydrogen chloride.

Example 329

N- ethyl1- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

1 g of 2-amino-3-bromo-5-carboxy-benzyl alcohol is heated with

3 g of N-ethyl-cyclohexylamine and 1.5 g of butyric acid for 5 hours at 140°C. It is evaporated in vacuo and the residue is purified by chromatography on silica gel with methanol as eluent. From the eluate, the hydrochloride with melting point 227-229 C (splitting.) is obtained with hydrochloric acid.

in

Example 330

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

2.7 g of 2-amino-3-bromo-5-carbethoxy-benzyl alcohol are heated with 3 g of diethylamine and 2 g of butyric acid in an autoclave for 5 hours at 150°C. It is evaporated in vacuo and the residue is purified by chromatography on silica gel with toluene/acetone = 4:1 as eluent. The hydrochloride is obtained from the eluate with ethereal hydrochloric acid.

Melting point: 165-168°C.

Example 331

N- ethyl1- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

2.4 g of 2-amino-3-bromo-5-carboxy-benzyl alcohol are heated

with 3.3 g of N-ethyl-cyclohexylamine and 0.1 g of magnesium oxide for 5 hours at 150°C. The product obtained is then distributed between chloroform and water, the chloroform phase is dried and evaporated to dryness. The hydrochloride with a melting point of 227-229°C (decomposition) is brought to crystallization by taking up in ethanol and by adding ethereal hydrochloric acid.

Example 332

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

2.7 g of 2-amino-3-bromo-5-carbethoxy-benzyl alcohol are heated with 2.4 g of diethylamine and 0.2 g of magnesium oxide in an autoclave for 5 hours at 150-160°C. It is evaporated in a vacuum and the residue is chromatographed on silica gel with toluene/acetone = 4:1. The hydrochloride with a melting point of 165-168°C is obtained from the eluate with ethanol/hydrochloric acid.

Example 333

N- ethyl- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

2.5 g of 2-amino-3-bromo-5-carboxy-benzyl alcohol are heated

with 4 g of N-ethyl-cyclohexylamine and 0.1 g of sulfuric acid for 5 hours at 150°C. Excess N-ethyl-cyclohexylamine is distilled off in a vacuum and the residue is distributed between chloroform and dilute ammonia. The chloroform solution is dried and evaporated to dryness. The residue is chromatographed on silica gel with methanol and from the eluate the hydrochloride with a melting point of 227-229°C (dec.) is brought to crystallization with ethereal hydrochloric acid.

Example 334

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

2.7 g of 2-amino-3-bromo-5-carbethoxy-benzyl alcohol is heated with 2.4 g of diethylamine and 0.1 g of sulfuric acid in an autoclave for 5 hours at 150-160°C. It is evaporated in vacuo, the residue is distributed between

chloroform and dilute ammonia, the chloroform solution is evaporated and the residue is purified by chromatography on silica gel with toluene-acetone (4:1) as eluent. The hydrochloride with melting point 165-168°C is obtained from the evaporation residue from the eluate with ethanolic hydrochloric acid Example 335

N- ethyl1- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

2.9 g of 2-acetamino-3-bromo-5-carboxy-benzyl alcohol are stirred with 1.5 g of N-ethyl-cyclohexylamine in 20 ml of tetralin for 4 hours at 175°C. The solution is evaporated to dryness in vacuo, the residue is distributed between chloroform and water, the chloroform solution is evaporated to dryness and the residue is chromatographed on silica gel with methanol. The hydrochloride with a melting point of 227-229°C (dec.) is obtained from the eluate by adding ethereal hydrochloric acid.

Example 336

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

3.1 g of 2-acetamino-3-bromo-5-carbethoxy-benzyl alcohol is heated with 2.4 g of diethylamine in an autoclave for 5 hours at 150-170°C. The solution is evaporated and the residue is chromatographed on silica gel with toluene:acetone (4:1) as eluent. The hydrochloride with a melting point of 165-168°C is obtained from the filtrate with ethanolic hydrochloric acid.

Example 337

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

1 g of 3-acetoxymethyl-4-amino-5-bromo-benzoic acid ethyl ester is heated in an autoclave for 2 hours with 5 ml of diethylamine at 120°C.

After cooling to room temperature, the reaction mixture is evaporated to dryness in vacuo and the residue is purified by chromatography on silica gel (eluent:toluene:acetone = 4:1). The hydrochloride with a melting point of 165-168°C is obtained from the eluate using hydrogen chloride.

Example 338

N- ethyl- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

2.8 g of 3-acetoxymethyl-4-amino-5-bromo-benzoic acid are heated with 5 g of N-ethyl-cyclohexylamine for 5 hours at 120-130°C. The solution is evaporated to dryness in vacuo and the residue is purified by chromatography on silica gel with methanol as eluent. The hydrochloride with a melting point of 227-229°C (dec.) is obtained from the eluate with ethereal hydrochloric acid.

Example 339

2- amino- 3- bromo- 5- carbethoxy- N, N- diethyl- benzylamine i

2.7 g of 2-amino-3-bromo-5-carbethoxy-benzyl alcohol and 0.5 g of sodium hydride are boiled in 100 ml of absolute ether and 50 ml of absolute tetrahydrofuran for 6 hours. The solution is cooled to -70°C, 1.7 g of toluene sulphochloride in 30 ml of ether is added slowly, the mixture is heated with stirring to -30°C, cooled again to -70°C and 1.4 g of diethylamine is added. The cooling bath is removed and the mixture is stirred until it has reached room temperature. The solution is shaken with water,

the organic phase is separated, evaporated in vacuo and the residue chromatographed on silica gel with toluene/acetone (4:1). The hydrochloride with a melting point of 165-168°C is obtained from the eluate with hydrochloric acid.

Example 340

N- ethyl- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

3.2 g of (2-amino-3-bromo-5-carboxy-benzyl)-ethyl ether and

13.7 g of N-ethyl-cyclohexylamine are heated in the presence of acidic alumina at 200°C for 5 hours. The reaction mixture is then distributed between water and chloroform, the chloroform phase is washed with water, dried and evaporated. The residue is chromatographed on silica gel with methanol. The hydrochloride with a melting point of 227-229°C (dec.) is obtained from the eluate with hydrochloric acid.

Example 341

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

3.5 g of (2-amino-3-bromo-5-carbethoxy-benzyl)-phenyl ether and

6 ml of diethylamine is heated in an autoclave in the presence of acidic aluminum oxide for 5 hours at 180-200°C. The solution is evaporated, the residue is distributed between chloroform and water, the chloroform phase is dried, evaporated and the residue is chromatographed on silica gel with toluene-acetone (4:1). The hydrochloride with a melting point of 165-168°C is obtained from the eluate with ethanolic hydrochloric acid.

Example 342

N- ethyl1- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

4.7 g of N-(2-amino-3-bromo-5-carboxy-benzyl)-N,N-diethyl-methyl-ammonium iodide are heated with 10 g of N-ethyl-cyclohexylamine for 1 hour at 150°C. Excess N-ethyl-cyclohexylamine is distilled off in a vacuum and the residue is distributed between chloroform and dilute ammonia. The chloroform phase is washed with water, evaporated and the residue transferred by dissolving in ethanol and adding ethereal hydrochloric acid to the hydrochloride with melting point 227-229°C (dec.).

Example 343

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

4.4 g of N-(2-amino-3-bromo-5-carbethoxy-benzyl)-trimethyl-ammonium iodide are heated with 10 g of diethylamine in an autoclave for 1 hour at 150-170°C. The solution is evaporated in vacuo, the residue is distributed between chloroform and water, the chloroform solution is evaporated and the residue is chromatographed on silica gel with toluene-acetone (4:1) as eluent. The hydrochloride with a melting point of 165-168°C is obtained from the eluate with ethanolic hydrochloric acid.

Example 344

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

Dissolve 2 g of 3-bromo-5-carbethoxy-N,N-diethyl-benzylamine in 20 ml of ethanol and hydrate after adding 0.2 g of Raney nickel at room temperature and 5 ato hydrogen pressure. The catalyst is filtered off, the filtrate is evaporated in vacuo to dryness and the residue is purified by chromatography on silica gel (eluent: chloroform/ethyl acetate = 6:1) and the base is transferred to the hydrochloride with a melting point of 165-168°C.

Example 345

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

0.9 g of N-ethyl-2-amino-3-bromo-5-carbethoxy-benzylamine is heated with 0.4 ml of diethyl sulfate and 0.4 ml of 30% caustic soda with stirring for 15 minutes at 90°C. After cooling to room temperature, the mixture is extracted twice with chloroform. The chloroform extract is washed once with diluted caustic soda and twice with water and evaporated to dryness in vacuum after drying over sodium sulfate. The residue is taken up in isopropanol and transferred to 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine hydrochloride with isopropanolic hydrochloric acid.

Melting point: 165-168°C.

Example 346

N- ethyl- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

2.5 g of 2-amino-3-bromo-5-carboxy-benzaldehyde is heated with 8.5 g of N-ethyl-cyclohexylamine and 3.2 g of formic acid for 8 hours at 100°C. The mixture is evaporated to dryness in vacuo and the residue is chromatographed on silica gel (eluent: methanol). The hydrochloride with a melting point of 227-229°C (dec.) is obtained from the eluate with hydrochloric acid.

Example 347

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

2.7 g of 2-amino-3-bromo-5-carbethoxy-benzaldehyde, 5 g of diethylamine;

l

and 3 g of formic acid are heated for 6 hours at 120°C. The reaction mixture is distributed between dilute ammonia and chloroform, the chloroform phase is dried, evaporated to dryness and the residue is purified by chromatography on silica gel (eluent: toluene/acetone = 4:1). The hydrochloride with a melting point of 165-168°C is obtained from the eluate with hydrogen chloride in ethanol.

Example 348

2- amino- 3- bromo- 5- carb. sy-N-cyclohexyl-benzylamine

3.5 g of N-(2-amino-3-bromo-5-carboxy-benzylidene)-cyclohexylamine and 0.4 g of sodium hydroxide are dissolved in 30 ml of absolute ethanol and stirred with 0.5 g of sodium borohydride for 5 hours. Excess sodium borohydride is destroyed by the addition of hydrochloric acid to a pH value of

about. 3, the mixture is evaporated to dryness in vacuo, the residue is distributed between chloroform and dilute ammonia, the chloroform phase is evaporated to dryness, the residue is taken up in ethanol, and the dihydrochloride with melting point 261-262°C (dec.) is brought to crystallization by adding ethereal hydrochloric acid

Example 349 2-amino-3-bromo-5-carboxy-N-cyclohexyl-N-methyl-benzylamine

2.5 g of 2-amino-3-bromo-5-carboxy-benzyl alcohol and 15.3 g of N,N<*>,N"-tricyclohexyl-N,N',N"-trimethyl phosphoric acid triamide are heated

for one hour at 210° C. The mixture is cooled, the residue is distributed between chloroform and dilute hydrochloric acid, the hydrochloric acid solution is filtered over charcoal, made alkaline with ammonia, extracted with chloroform, the chloroform extract is dried and evaporated to dryness. The residue is dissolved in 1 ethanol and the hydrochloride with a melting point of 2 30-240°C is separated from it by the addition of ethereal hydrochloric acid.

Example 350

2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- N- methyl- benzylamine

2.5 g of 2-amino-3-bromo-5-carboxy-benzyl alcohol and 10 g of N-cyclohexyl-N-methylacetamide are heated for 5 hours at 170°C. Excess amide is distilled off and the residue is purified by chromatography on silica gel with methanol as eluent. By addition of ethereal hydrochloric acid and evaporation, the hydrochloride with melting point 2 30-2 40°C is obtained from the eluate.

Example 351

2- benzoylamino- 3- bromo- 5- carbethoxy- N, N- diethyl- benzylamine

3.6 g of 8-bromo-6-carbethoxy-2-phenyl-4H-3,1-benzoxazine hydrobromide is heated with 4.4 g of diethylamine in an autoclave for 2 hours at

150-160°C, after which the reaction mixture is evaporated to dryness in vacuum. The residue is distributed between chloroform and dilute ammonia, the chloroform phase is evaporated, the residue is dissolved in ethanol and the hydrochloride with a melting point of 220-222°c is precipitated with ethereal hydrochloric acid.

Example 352

N- ethyl1- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

0.6 g of N-ethyl-2-amino-3-bromo-5-carbamoyl-N-cyclohexyl-benzylamine is dissolved in 45 ml of concentrated hydrochloric acid and boiled for 40 minutes] On cooling, a precipitate crystallizes out which is suctioned off. Recrystallization from ethanol gives the hydrochloride with a melting point of 227-229°C (dec.).

Example 353

N- ethyl1- 2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

1 g of N-ethyl-2-amino-3-bromo-N-cyclohexyl-5-cyano-benzylamine is boiled with 45 ml of concentrated hydrochloric acid for 40 minutes. The reaction mixture is poured onto ice, neutralized with ammonia and freed by filtration from a small amount of insoluble material. The filtrate is extracted with ether, the ether extract is evaporated to dryness, from the residue obtained by dissolving in ethanol and adding ethereal hydrochloric acid the hydrochloride with a melting point of 227-229°C (dec.).

Example 354

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

1 g of 2-amino-3-bromo-5-cyano-N,N-diethyl-benzylamine is dissolved in

50 ml absolute ethanol. The solution is saturated with hydrogen chloride, boiled for 10 hours and boiled for a further 5 hours after adding 5 ml of water. Then evaporate to dryness in vacuo. The crude product is transferred into the base and purified by chromatography on silica gel (eluent: ethyl acetate). After evaporation of the eluate, the obtained residue is transferred into the hydrochloride with a melting point of 165-1.68°C with isopropanolic hydrochloric acid.

Example 355

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

5 g of 2-amino-3-bromo-5-carboxy-N,N-diethyl-benzylamine are dissolved in 150 ml of absolute ethanol. This solution is saturated with hydrogen chloride, boiled for 1 hour and then evaporated to dryness in vacuo. Crystallization of the residue from ethanol yields the hydrochloride with a melting point of 165-168°C.

in

Example 356

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

Dissolve 0.7 g of 2-amino-3-bromo-5-carbomethoxy-N,N-diethyl-benzylamine in 75 ml of absolute ethanol, add 0.02 g of sodium hydroxide,

boiled for 15 minutes and then evaporated to dryness in vacuo. The residue is distributed between water and chloroform, the chloroform solution is dried and evaporated to dryness. The residue is transferred with ethereal hydrochloric acid to the hydrochloride with a melting point of 165-168°C.

Example 357

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

3 g of 2-amino-3-bromo-5-carboxy-N,N-diethyl-benzylamine are heated with 9 ml of thionyl chloride in 30 ml of toluene for 1 hour at approx. 100°C

and then evaporated to dryness in vacuo. The 4-amino-3-bromo-5-(N,N-diethyl)-aminomethyl-benzoyl chloride hydrochloride thus obtained is stirred in a solution of 1 g of sodium in 20 ml of absolute ethanol for 3 hours. The mixture is evaporated to dryness in vacuo and the residue is distributed

between chloroform and water, the chloroform phase is dried and evaporated to dryness. The hydrochloride with a melting point of 165-168°C is obtained from the residue by dissolving in ethanol and adding ethereal hydrochloric acid.

Example 358

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine

1.1 g 2-amino-3-bromo-5-carbamoyl-N,N-diethyl-benzylamine

dissolve in 30 ml of absolute ethanol. The solution is saturated with hydrogen chloride and boiled for 6 hours. The mixture is evaporated to dryness in vacuo and the residue is distributed between chloroform and dilute ammonia. The chloroform solution is evaporated and the residue is purified by chromatography

on silica gel (eluent: toluene/acetone = 4:1). From the evaporation residue from the eluate, the hydrochloride with a melting point of 165-168°C is obtained from ethanol with ethereal hydrochloric acid.

Example 359

N-(2-amino-5-carboxy-benzyl)-hexamethyleneamine

Melting point of the dihydrochloride: from 121°C (dec.).

Prepared from 2-amino-5-carboxy-benzyl bromide and hexamethyleneamine analogously to example 25.

Example 360

2- amino- 3- bromo- 5- carbetoxy- N- cyclohexyl- N- methyl- benzylamine Melting point of the hydrochloride: 212-215°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-benzyl bromide and N-methyl-cyclohexylamine analogous to example 25.

Example 361

2- amino- 3- bromo- 5- carbethoxy- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine

Melting point of the hydrochloride: 137°C (dec.).

Prepared from 2-amino-3-bromo-5-carbethoxy-benzyl bromide and trans-4-hydroxy-cyclohexylamine analogous to example 25.

Example 362

N-(2-amino-3-bromo-5-carbethoxy-benzyl)- hexamethyleneamine The melting point of the hydrochloride: 219-221°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-benzyl bromide and hexamethyleneamine analogous to example 25.

Example 36 3

N- ethyl- 2- amino- N- cyclohexyl- 5- methyl- benzylamine Melting point of the hydrochloride: 189-191°C (dec.).

Prepared from 2-amino-5-methyl-benzyl bromide and N-ethyl-cyclohexylamine analogously to example 25.

Example 364

2- amino- 3- bromo- 5- cyano- N- cyclohexyl- N- methyl- benzylamine The melting point of the hydrochloride: 236-240°C.

Prepared from 2-amino-3-bromo-5-cyano-benzyl bromide and N-methyl] cyclohexylamine analogously to example 25.

Example 365

2- amino- 3- bromo- 5- carbamoyl- N, N- diethyl- benzylamine Melting point: 140-142°C.

Prepared from 2-amino-3-bromo-5-carbamoyl-benzyl bromide and diethylamine analogously to Example 25.

Example 366

2- amino- 5- bromo- N, N- diethyl- 3- trifluoromethyl- benzylamine Melting point of the hydrochloride: 198-200°C.

Prepared from 2-amino-5-bromo-3-trifluoromethyl-benzyl bromide and diethylamine analogously to example 25.

Example 367

2- amino- 5- bromo- N, N- diethyl- 3- methyl- benzylamine Melting point of the hydrochloride: 177-179°C (dec.).

Prepared from 2-amino-5-bromo-3-methyl-benzyl bromide and diethylamine analogously to example 25.

Example 368 N-ethyl-2-amino-5-bromo-N-cyclohexyl-3-methyl-benzylamine

Melting point of the dihydrochloride: 183-187°C (dec.).

Prepared from 2-amino-5-bromo-3-methyl-benzyl bromide and

N-ethyl-cyclohexylamine analogous to example 25.

Example 369

N-(2-amino-5-bromo-3-methyl-benzyl)-hexamethyleneamine

Melting point of the dihydrochloride: 159-164°C (dec.).

Prepared from 2-amino-5-bromo-3-methyl-benzyl bromide and hexamethyleneamine analogously to example 25.

Example 370

2- amino- 5- bromo- 4- tert. butyl-N-cyclohexyl-N-methyl-benzylamine

Melting point of the hydrochloride: 202-202.5°C (dec.).

Prepared from 2-amino-5-bromo-4-tert-butyl-benzyl bromide and

N-methyl-cyclohexylamine analogous to example 25.

Example 371 I N-(2-amino-5-bromo-4-tert.butyl-benzyl)-morpholine

Melting point of the dihydrochloride: 194-198°C (dec.).

Prepared from 2-amino-5-bromo-4-tert-butyl-benzyl bromide and

morpholine analogue example 25.

Example 372

2- amino- 5- bromo- N-( trans- 4- hydroxy- cyclohexyl)- N- methyl- 3-[ N- methyl-( trans- 4- hydroxy- cyclohexylamino)- methyl]- benzylamine

Melting point: 179-180°C.

Prepared from 2-amino-5-bromo-3-hydroxymethyl-benzyl alcohol,

thionyl chloride and N-methyl-trans-4-hydroxy-cyclohexylamine analogously

example 1.

Example 373 2-amino-3-bromo-N,N-dimethyl-5-methoxy-benzylamine

Oil, structural evidence by IR, UV and NMR spectra.

Prepared from 2-amino-3-bromo-5-methoxy-benzyl bromide and

dimethylamine analogous to example 25.

Example 374

N-(5-acetyl-2-amino-benzyl)- hexamethyleneamine The melting point of the hydrochloride: 205-207°C (dec.).

Prepared from 5-acetyl-2-amino-benzyl bromide and hexamethyleneamine analogously to example 25.'

Example 375

5- acetyl- 2- amino- 3- bromo- N, N- dimethyl- benzylamine

Melting point: 92-95°C.

Prepared from 5-acetyl-2-amino-3-bromo-benzyl bromide and dimethylamine analogously to example 25.

Example 376

5- acety1- 2- amino- N, N- dimethyl- benzylamine

Melting point of the hydrochloride: 209-215°C (dec.).

Prepared from 5-acetyl-2-amino-benzyl bromide and dimethylamine analogously to example 25.

Example 377

N-ethyl-2-amino-3-bromo-N-cyclohexy1-5-(1-hydroxy-ethyl)-benzylamine Melting point: 117-121°C.

Prepared from 2-amino-3-bromo-5-(1-hydroxyethyl)-benzyl bromide and N-ethyl-cyclohexylamine analogous to example 25.

Example 378

2- amino- 3- bromo- 5- carbetoxy- N, N- diethyl- benzylamine Melting point of the hydrochloride: 165-168°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-benzyl-pyridinium bromide and diethylamine analogously to example 34 3.

Example 379

N- ethyl- 2- amino- 3- carboxy- N- cyclohexyl- benzylamine

Melting point of the hydrochloride: 19 3-197°C.

Prepared from 2-amino-3-carboxy-benzyl bromide and N-ethyl-cyclohexylamine analogous to example 25.

Example 380

N- ethyl- 2- amino- 5- bromo- 3- carboxy- N- cyclohexyl- benzylamine The melting point of the hydrochloride: 130-140°C.

Prepared from 2-amino-5-bromo-3-carboxy-benzyl bromide and N-ethyl-cyclohexylamine analogous to example 25.

Example 381

2- amino- 3- bromo- 5- carboxy- N- cyclohexyl- benzylamine

3.5 g of 2-amino-3-bromo-5-carboxy-N-cyclohexylidene-benzylamine and 0.4 g of sodium hydroxide are dissolved in 30 ml of absolute ethanol and stirred for 5 hours with 0.5 g of sodium borohydride. Excess sodium borohydride is destroyed by adding hydrochloric acid to a pH value of approx. 3, evaporated to dryness in vacuo, the residue distributed between

chloroform and dilute ammonia, the chloroform phase is evaporated to dryness, the residue is taken up in ethanol and by adding ethereal hydrochloric acid, the dihydrochloride with melting point 261-262°C (splitting) is brought to crystallization.

Claims (3)

1. Analogous process for the preparation of pharmacologically active benzyl amines with the general formula I where R 1 is a hydrogen atom or a lower alkanoyl- or an optionally with halogen substituted benzoyl group, R 2 is a hydrogen, chlorine or bromine atom, R 2 is a fluorine atom; a methyl group in the 3-, 4- or 5-position, or, when R-^ means a lower alkanoyl group or an optionally halogen-substituted benzoyl group or when R 2 means a chlorine or bromine atom, also in the 2- or 6-position in the phenyl nucleus ; a linear or branched alkyl residue with 2-4 carbon atoms; a trifluoromethyl, cyano, carbamoyl, carbalkoxy, acetyl or 1-hydroxyethyl group; a carboxyl group when at least one of the radicals R 1 , R 2 , R 1 or R 1 does not mean a hydrogen atom; a lower alkoxy group in the 3-, 4- or 5-position, or, when R 2 means a chlorine or bromine atom, also in the 2- or 6-position of the phenyl nucleus; or an aminomethyl group of the formula: where Rg and R^, which may be the same or different, mean lower alkyl, cycloalkyl or hydroxycycloalkyl groups with 5-7 carbon atoms or together with the nitrogen atom form a pyrrolidine, piperidine or morpholine ring, R 4 and R 5 which may be the same or different, are hydrogen atoms, linear or branched alkyl radicals with 1 to 5 carbon atoms which may be substituted with 1 or 2 hydroxy groups, alkenyl radicals with 2 to 4 carbon atoms, cycloalkyl radicals with 5 to 7 carbon atoms which are optionally substituted with one or two hydroxy groups, benzyl, morpholinocarbonylmethyl groups or together with the nitrogen atom a pyrrolidine-, piperidine-, i hexamethyleneamine-, morpholine-, N-methylpiperazine- or | camphidin ring, and their physiologically compatible acid addition salts with inorganic or organic acids, characterized in that a) a compound of the general formula II where and R2 are as indicated above, R^' is the residue -CH2~X or they have for R^ initially an given meanings, and X means a chlorine, bromine or iodine atom, a hydroxy group, an acyloxy, sulfonyloxy, alkoxy, aryloxy or aralkoxy radical, a trialkylammonium group or a pyridinium radical, is reacted with an amine of the general formula III where R^ and R^ are as indicated initially, or b) for the preparation of compounds with the general formula I where R2 means a chlorine or bromine atom, and R^ and/or R^ are as indicated initially with the exception of an alkenyl residue, is halogenated a compound of the general formula IV where and R^ are as indicated at the beginning, and R4' and R5 <1> have the meanings indicated for R4 and R5 at the beginning with the exception of alkenyl, or c) for the preparation of compounds with the general formula in where R^ and/or R4 means a hydrogen atom, one or two protecting residues from a compound of the general formula v where R2, Rg and R,, are as indicated at the outset, Y, means a hydrolytically or hydrogenolytically cleavable protective residue for an amino group or has the meanings given for R^ at the beginning, and Y2 means a hydrolytically or hydrogenolytically cleavable protective residue for an amino group or has the meanings given for R^ at the beginning, with at least one of the residues Y^ and Y2 meaning a protective residue, or d) for the preparation of compounds of the general formula I where R^ means a 1-hydroxyethyl group, a compound is reduced with the general formula VI where R , R 2 , R 4 and R 1 are as indicated at the outset, or e) for the preparation of compounds with the general formula in which R 2 denotes a carboxyl group, a compound is hydrolyzed see with the general formula (VII) where R^, R2, R4 and Rj- are as indicated at the beginning, and A means a functional derivative of a carboxyl group, or f) for the preparation of compounds with the general formula in which R^ means a hydrogen atom, R^ is as indicated at the beginning with the exception of a cyano, carboxyl, carbalkoxy, carbamoyl or acetyl group, and R4 and/or R4 does not represent a morpholinocarbonylmethyl residue, a compound is reduced by the general formula VIII where R 2 and R 4 and R 4 with the exception of a morpholinocarbonylmethyl residue and R^ with the exception of a cyano, carboxyl, carbamoyl, carbalkoxy and acetyl group are as indicated at the outset, or in g) a compound of the general formula IX where 1*2 to R,, is as indicated at the outset, is reduced, or h) for the preparation of compounds of the general formula I where R,, does not mean a residue which is substituted by one or more hydroxy groups, andR 4 and/or R,, does not mean hydrogen, a compound of the general formula x is alkylated R, R 3 in R 3 and R 3 are as indicated at the outset, with a compound of the general formula XI where R5" have the meanings given initially for R5, except taking hydrogen and the residues which are substituted with one or two hydroxyl groups, and W means a halogen atom or a sulfonic acid residue, or i) for the preparation of compounds of the general formula I where R does not mean an acetyl group, an aldehyde of the general formula XII is reacted where R10, R2 are as initially indicated, and R^" has the meanings indicated for R^ initially with the exception of an acetyl group, with an amine of the general formula III where R^ and R,, are as indicated at the outset, resp. with the corresponding formamide in the presence of formic acid, or for the preparation of compounds of the general formula i where R^ means a hydrogen atom and R^ is as indicated initially with the exception of an acetyl group, a compound of the general formula XIII is reduced or a compound of the general formula Xlla where R1 'R2°^R5 are as indicated below, R^" have the meanings given initially for R^ with the exception of an acetyl group, and Z means a cyclohexylidene residue which is optionally substituted with one or two hydroxy groups, an alkylidene residue with 3 to 5 carbon atoms or a morpholinocarbonylmethylidene residue, or k) for the preparation of compounds of the general formula I where R does not mean a 1-hydroxyethyl group, a compound is reacted with the general connection XIV where R^ and R2 are as indicated at the beginning, and R^"1 have the meanings indicated for R^ at the beginning with except for a 1-hydroxyethyl group, with an amide of the general formula XV where R^1" means a hydrogen atom or an alkyl radical with 1 to 3 carbon atoms, and Rj-<1>" means an alkyl residue with 1 to 3 carbon atoms, or a cyclohexyl group, or R^'" and R,."' together with the nitrogen atom means a morpholino or piperidine residue, or with an amide of the general formula xva where R 5 and R 5 are as indicated at the outset, and Ro 5 means an alkyl, aryl or aralkyl residue, or 1) a compound of the general formula XVI where R2 and is, as indicated at the outset, Rg is a hydrogen atom, an alkyl, aryl, aralkyl or hydroxy group, is reacted with an amine of the general formula III where R^ and R,, are as indicated at the outset, and optionally the reaction product obtained is then hydrolyzed, or m) for the preparation of compounds of the general formula I where R^ denotes a carbolicoxy group, a compound of the general formula XVII is reacted where R 1 , R 2 , R 4 and R 1 are as indicated at the outset, and B means a carboxyl group or a functional derivative hence, with a compound of the general formula XVIII where R^Q means a lower alkyl residue and D means a hydroxyl group or a halogen atom, and a compound obtained according to methods a to m with the general formula i where R3 denotes a cyano group, optionally transferred by partial hydrolysis to the corresponding carbamoyl compound with the general formula i, and/or optionally acylated a compound obtained with the general formula I where R-^means a hydrogen atom, and R2, R3 / R4 and R,, are as stated at the beginning with the exception of residues containing a reactive hydrogen atom, and/or an obtained compound of the general formula I is optionally transferred to the physiologically compatible salts thereof with inorganic or organic acids. 2. Process as stated in claim 1 for the production of 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine hydrochloride, characterized in that starting materials are used where the substituents have or are transferred to the following meanings: NHR-^: 2-amino, R2: 3-bromo, R3: 5-carbethoxy, NR^R^: diethylamino. 3. Process as stated in claim 1 for the production of N-ethyl-2-amino-3-bromo-5-carboxy-N-cyclohexyl-benzylamine hydrochloride, characterized in that starting materials are used where the substituents have or are transferred to the following meanings : NHR-^: 2-amino, R2: 3-bromo, R3: 5-carboxy, NR^R^: N-ethyl-cyclohexylamino.