IE40146B1 - Substituted aminobenzylamines - Google Patents

Abstract

The preparation of novel benzylamines of the formula I <IMAGE> in which the symbols R1 to R5 have the meanings stated in Claim 1, as well as their physiologically tolerated acid addition salts with inorganic or organic acids is described. The compounds of the formula I have valuable pharmacological properties, especially an antiulcer effect, a secretolytic, cough-suppressant effect and an effect enhancing the production of the surfactant or antiatelectasis factor in the alveoli. The compounds of the formula I are prepared by hydrolysing corresponding compounds which, in place of the carboxyl group R3, have a functional derivative of the carboxyl group as substituent. [GB1469187A]

Description

4 0 1 4 G The present Invention relates to new benzylamlnes having interesting physiological properties.

According to one feature of the present Invention there are provided compounds of general formula Lwherein Rj represents a hydrogen atom, an aliphatic acyl group or an optionally substituted aromatic acyl group; R, represents a hydrogen, chlorine or bromine atom; Kj represents a fluorine atom: a methyl group in the 3-, 4- or 5-position of the phenyl nucleus; a methyl group in the 2- or 6- position of the phenyl nucleus; when at least one of Rj and R^ is other than a hydrogen atom; a straight or branched chain alkyl group with 2 to 4 carbon atoms; a trifluoromethyl , cyano, carbamoyl, carbalkoxy, acetyl or 1-hydroxyethy1 group; a carboxyl group when at least one of U | , K^, and R(j is other than a hydrogen atom; an alkoxy group in the 3-, 4- or 5-position of the phenyl nucleus; an alkoxy group in the 2- or 6-position of the phenyl nucleus when represents a chlorine or bromine atom; or a group of formula R 3 R (I) /«6 CH2NNs^ 4 0 11 G (wherein Rg and R^, which may be the same or different, each represents an alkyl, cycloalkyl or hydroxycycloalkyl group or Kb and Rj together with the nitrogen atom to which they are attached represent a pyrrolidine, piperidine or morpholine ring); * R4 and Rj, which may be the same or different, each represents a hydrogen atom, a straight or branched chain alkyl group with 1 to 5 carbon atoms which may optionally be substituted by 1 or 2 hydroxy groups, .in alkenyl group with 2 to 4 carbon atoms, a cycloalkyl group with 5 to 7 carbon atoms which may u optionally be substituted by 1 or 2 hydroxy group, a benzyl group or a morpholinocarbonylmethyl group; or R4 and together with the nitrogen atom to which they are attached represent a pyrrolidine, piperidine, hexamethylene-anine, morpholine, N-met hy 1-pi peraz i ne or camphidine ring"] '■> and acid addition salts thereof. !n general the compounds of general formula I and physiological compatible acid addition salts thereof possess valuable physiological properties, in particular an anti-ulcus activity, a secretolytic and antitussive activity, and a stimulat- u Ing dfeet on the production of the surfactant or antiatelectasis factor of the al veol i.

Preferred compounds of general formula I and physiologically coapatible acid addition salts thereof by virtue of their especially favourable physiological properties are those 5 [wherein Rj represents a hydrogen atom or an acetyl group; represents a hydrogen, chlorine or bromine atom; represents a fluorine atom; a methyl group in the 3-, 4- or b-position of the phenyl nucleus; a methyl group on the 2- or 6-position of the phenyl nucleus when at least one of 3 , /"6 CH2Nn^ 4 0116 (wherein Rfi and R^, which may be the same or different, each represents an alkyl, cycloalkyl or hydroxycycloalkyl group or Rfe and Ry together with the nitrogen atom to which they are attached represent a pyrrolidine, piperidine or morpholine ring) R4 and Rg, which may be the same or different, each represents a hydrogen atom, a straight or branched chain alkyl group with 1 to 5 carbon atoms which may optionally be substituted by 1 or 2 hydroxy groups, .in alkenyl group with 2 to 4 carbon atoms, a cycloalkyl group with 5 to 7 carbon atoms which may optionally be substituted by 1 or 2 hydroxy group, a benzyl group or a morpholinocarbonylmethy1 group; or R4 and R^ together with the nitrogen atom to which they are attached represent a pyrrolidine, piperidine, hexamethylene-amine, morpholine, N-methy1-piperazine or camphidine ring^] and acid addition salts thereof.

In general the compounds of general formula I and physiological compatible acid addition salts thereof possess valuable physiological properties, in particular an anti-ulcus activity, a secretolytic and antitussive activity, and a stimulating effect on the production of the surfactant or antiatelectasis factor of the alveoli.

Preferred compounds of general formula I and physiologically compatible acid addition salts thereof by virtue of their especially favourable physiological properties are those [wherein Rj represents a hydrogen atom or an acetyl group; Rj, represents a hydrogen, chlorine or bromine atom; represents a fluorine atom; a methyl group in the 3-, 4- or b-position of the phenyl nucleus; a methyl group on the 2- or 6-position of the phenyl nucleus when at least one of 4 0 1-11* Rj and is other than a hydrogen atom; a straight or branched chain alkyl oroup with 2 to 4 carbon atoms; a tr1fluoromethyl, cyano, carbamoyl, carbethoxy, acetyl or 1-hydroxyethyl group; a carboxyl group when at least one of Rj, R2, R4 and Rfi Is 5 other than a hydrogen atom; a methoxy group In the 3-, 4- or b-positlon of the phenyl nucleus; a methoxy group 1n the 2- or 6-position of the phenyl nucleus when Rg represents a chlorine or bromine atom; or a group of formula ch2-n (wherein and R^, which may be the same or different, n> each represents a methyl, cyclohexyl or hydroxycyclohexyl group; or R^ and R7 together with the nitrogen atom to which they are attached represent a pyrrolidine, piperidine or morpholine ring); and R4 and R^, which may be the same or different, each represents a methyl, ethyl, cyclohexyl or hydroxycyclohexyl group; or R4 and R^, together with the nitrogen atom to which they are both attached, represent a pyrrolidine, piperidine, hexamethyleneamine, morpholine or N-methyl piperazine ring} and physiologically compatible acid salts thereof. 4 4 0 1 J 6 The following ore such compounds which are |v»rt iculnrly preferred:- 2ft m i no- t—1» roino- 5-ca rbeLhoxy-N, N-d i e thy 1 -benzy I ami ne and physiologically compatible acid addition salts thereof ; N-ethy I -2-amino-3-bronio-'»-carboxy-N-cyc lohcxy I -ben/.y I ami ne and physiologically compatible acid addition salts thereof; N-fthy I -2-ami no-!»-l»romo-N-cyc I ohexy 1-1-f luoro-ben/.y l.-nni ne and physiologically compatible acid addition salts thereof ; N-( 2-aini no-li-broino-3-methy I -benzyl )-hexamethy leneamine and physiologically compatible acid addition salts thereof ; N-( 2-ami no-r>-broino-4-Lerl.. -buty 1 - benzy 1 )-morpho I i ne ami physiologically compatible acid a<ldiLion salts thereof ; 2-;iiui no- $-bromo-N,N-dimet.hy I — *»— f 1 uoro-benzy lami ne and physiologically compatible acid addition salts thereof. 15 The new compounds according to the invention may be prepared by any of the following processes, which processes constitute further features of the present invention: a) Reaction of a compound of formula 40146 ch2- x II R 2 n \r 1 (wherein R^ and R2 are as hereinbefore defined, R^' represents the group -Cf^-X or is as hereinbefore defined for R^> and X represents a chlorine, bromine or iodine atom or a hydroxy, acyloxy, sulfonyloxy, alkoxy, aryloxy, nralkoxy, trLalkylammonium or pyrldinlum group) with a compound of formula (wherein R^ and R^ are as hereinbefore defined).

Suitable compounds of general formula II include those wherein X represents a chlorine or bromine atom, or a hydroxy, acetyloxy, butyryloxy, benzoyloxy, methylsulfonyloxy, p-toluenesulfonyloxy, methoxy, ethoxy, phenoxy, trimethylammonium or pyridinium group. X can in general represent any group which on detachment from a compound of formula II permits the temporary formation of a benzyl cation. 5 (HI) 40146 such as triethylamine, pyridine or in an excess of the amine of general formula III. The tertiary organic base may conveniently nt the same lime serve ns a solvent.

If X represents an acyloxy group, for example an acetoxy or benzoyloxy group, or an alkoxy, aryloxy or aralkoxy group, the reaction may if desired be carried out in the presence of an acid catalyst, such as ammonium chloride, acidic aluminium oxide or sulfuric acid, and is preferably effected at temperatures from 0 to 2<><>"C.

If X represents a hydroxyl group, the reaction is advantageously performed in the presence of an acid catalysl (e.g. sulfuric acid,hydrobromic acid or p-toluenesulfonic acid or a lower carboxylic acid such as propionic acid or butyric acid) or in the presence of an alkaline catalyst, (e.g. potassium hydroxide, magnesium oxide or sodium amide) and is preferably effected nt Lemperatures front 120 to 180°C. The reaction may, however, also be performed in the absence of a solvent.

If X represents a triaIkylammonium or pyridiilium group, the reaction is preferably carried out in an excess of the amine of general formula III which excess serves as solveni, and at temperatures from 120 to I80"C. 40146 The reaction may, however, also be performed in the absencc of a solvent.

I>) For the prep;ir;U ion of compounds of >;eiter;il formula I (wherein R., R ,, R, ami R-, are as hereinbefore I .} b 7 defined, R^ represents a chlorine or bromine atom, and R^ and R,. are as hereinbefore defined with the proviso that they do not represent alkenyl groups): llalogenaLion of a compound of formula (IV) 9 40110 (wherein R^ and are as hereinbefore defined and R.' and R_' are as hereinbefore defined for R, and Rc A 5 4 5 with the proviso that they do not represent alkenyl groups). *> The reaction is effected by means of a halogenating agent, e.g. with chlorine, bromine, tribromophenyl hypobromite or lodosobenzene dichloride, preferably in the presence of a solvent (e.g. in 50-100% acetic f acid, methylene chloride or tetrahydrofuran) and in 10 the presence of a tertiary organic base such as triethylamine or pyridine. The reaction is conveniently effected at temperatures from -20 to 50°C. 1 male of the halogenating agent or a slight excess thereof is generally used per mole of the compound of formula IV, 15 present as the free base or as a salt, for example as the mono-, di- or trihydrochloride. If a hydrohalic acid salt is formed during the reaction, it may be isolated as such or, if desired, it may be further purified via the base. 20 c) For the preparation of compounds of general formula I, as hereinbefore defined with the proviso that and/or represent hydrogen atoms: - 10 - 4 0116 Removal of one or two protecting groups from a compound of formula (wherein R3 and are as hereinbefore dsfined, Y^ represents a hydrolytically or hydrogenolytically 5 removable protecting group for an amino group or is as hereinbefore defined for R^ and represents a hydrolytically or lyduqgenolytica 1 ly removable protecting group for an amino group or is as hereinbefore defined for R^ with the proviso that e.t least one of and 10 Y^ represents a protecting group).

If and/or in the compound of formula V represent acyl groups (for example acetyl, benzoyl, p-toluenesulfonyl, trimethylsilyl or tetrahydropyranyl-(2) groups) these groups are preferably split off 15 hydrolytically in the presence of a solvent, e.g. by means of ethanolic hydrochloric acid or aqueous alcoholic sodium hydroxide solution. The hydrolysis - 11 - 4 0 110 is conveniently effected at temperatures from 20 to 150°C, preferably, however, at the boiling temperature of the solvent used. If a compound of formula V wherein represents a cyano, carbalkoxy or carbamoyl 5 group is used, this group may simultaneously be sapon ified to the carboxyl group.

If and/or Y2 in the compound of formula V represent benzoxycarbonyl or benzyl groups, these groups may be split off by hydrogenation, for example using 10 hydrogen in the presence of a catalyst such as palladium, preferably in the presence of a solvent (e.g. methanol, methanol/water or methanol/hydrochloric acid) and preferably at room temperature. During the reaction any alkenyl group present as R^ and/or R^ may be 15 converted into the corresponding alkyl group and any acetyl and cyano groups present as R^ may also be reduced at the same time. d) For the preparation of compounds of general formula 1 as hereinbefore defined, wherein R^ represents the 20 1-hydroxyethyl group: Reduction of a compound of formula (VI) - 12 40146 (wherein Rj, R2, R^ and R,. are as hereinbefore defined).

The reduction is preferably carried out in the presence of a solvent, suitable solvents including methanol, methanol/water, ethanol, isopropanol, ether, tetrahydrofuran and dioxane. The reduction is conveniently effected by means of a complex metal hydride (e.g. lithium aluminium hydride or more preferably sodium borohydride), an aluminium alcoholate (such as aluminium isopropoxide) in the presence of a primary or secondary alcohol (such as ethanol or isopropanol) or hydrogen in the presence of a catalyst (such as Raney nickel, platinum or palladium/animal charcoal) conveniently at temperatures from -20° up to the boiling temperature of the solvent used.

If the reduction is effected with catalytically activated hydrogen, any alkenyl groups present as R^ and/or R^ may be simultaneously converted into the corresponding alkyl groups and/or any benzyl groups present may be split off hydrogenolytically. e) For the preparation of compounds of general formula 1 as hereinbefore defined, wherein R^ represents the carboxyl group: Hydrolysis of a compound of formula - 13 - 4 0116 R R 2 (VII) A 1 (wherein Rj, R2, and Rg are as hereinbefore defined and at least one being other than a hydrogen atom and A represents a functional derivative of the carboxyl group).

Suitable functional groups A include for example amides, iminoesters, esters and nitriles.

The reaction is conveniently carried out in the presence of a solvent (e.g. methanol, ethanol, methanol/water, ethanol/ water, dioxane/water or water) preferably in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid or in the presence of a base such as sodium hydroxide and at temperatures from 50 to 150°C, preferably, however, at the boiling temperature of the solvent used. If a compound of formula VII wherein Rj represents an acyl group is used, this group may be simultaneously split off during the reaction. f) For the preparation of compounds of general formula I (wherein Rj represents a hydrogen atom, R^ is as hereinbefore defined, R^ is as hereinbefore defined with the proviso that it cannot represent a cyano, carboxyl, carbalkoxy, carbamoyl or acetyl group, and and R^ - 14 - 40146 are as hereinbefore defined with the proviso that they do not represent morpholinocarbonylmethyl groups): Reduction of a compound of formula (VIII) "2 (wherein R^ is as hereinbefore defined, R^ is as hereinbefore 5 defined with the proviso that it cannot represent a cyano, carboxyl, carbamoyl, carbalkoxy or acetyl group, and R^ and R,. are as defined in claim 1 with the proviso that neither of R^ and R^ represent a morpholinocarbonylmethyl group). 10 The reduction is conveniently effected in the presence of a solvent, and preferably by means of nascent hydrogen (e.g. sodium in ethanol), catalytically activated hydrogen or a complex metal hydride (e.g. sodium borohydride in pyridine or advantageously lithium 15 aluminium hydride in ether or tetrahydrofuran). The reduction is preferably effected at slightly elevated temperatures, e.g. at temperatures from 30 to 70"C, or - 15 - 40146 at the boiling temperature of the solvent used. g) For the preparation of compounds of general formula I as hereinbefore defined wherein represents a hydrogen atom: Reduction of a compound of formula R< CH. ' (IX) 2 (wherein R^, R^, R^ and R^ are as hereinbefore defined).

The reduction is conveniently effected in the presence of a solvent such as water, methanol, ethanol, ' water/methanol or ethyl acetate, and preferably by means 10 of nascent hydrogen (e.g. zinc/glacial acetic acid or iron/hydrochloric acid), hydrogen in the presence of a catalyst (e.g. Raney nickel, platinum or palladium/ coal), a complex metal hydride such as lithium aluminium hydride, or tin(ll) chloride/hydrochloric acid, The reduction is 11 conveniently effected at temperatures from 0 to 100°C.

For the preparation of a compound of formula I, wherein R^ represents an acetyl group and/or R^ and/or R,. represent alkenyl groups, the reaction is preferably - 16 - 40146 effected by means of tin(II) chloride/hydrochloric acid.

Compounds of general formula I wherein represents an acyl group are prepared by effecting the reduction by means of catalytically activated hydrogen in the 5 presence of the corresponding carboxylic acid anhydride. h) For the preparation of compounds of general formula 1 as hereinbefore defined with the proviso that does not represent a group substituted by one or two hydroxyl groups or a hydrogen atom: 10 Reaction of a compound of formula (X) 1 (wherein Rj, R2, R3 and R^ are as hereinbefore defined) with a compound of formula R5" W (XI) (wherein R^" is as hereinbefore defined for R,- with the proviso that it does not represent a hydrogen atom or a 15 group substituted by one or two hydroxyl groups, and W represents a halogen atom or a sulfonic acid group). - 17 - 40146 10 Hie reaction is advantageously carried out in the presence of a solvent, for example methanol, dioxane or dimethylformamide, and is conveniently effected at temperatures from -20 to 150°C, preferably, however, at the boiling point of the solvent used.

Compounds of general formula I as hereinbefore defined where represents a methyl group may be conveniently prepared by reacting the corresponding compound of formula X as hereinbefore defined with formaldehyde in the presence of formic acid preferably at elevated temperatures, for example at the boiling point of the reaction mixture. i) For the preparation of compounds of general formula I as hereinbefore defined with the proviso that R^ does not represent an acetyl group: Reaction of a compound of formula (wherein R^ and R^ are hereinbefore defined and R^" is as hereinbefore defined for R^ with the proviso that CHO (Xll) 18 40146 it does not represent an acetyl group) with a compound of formula (wherein R^ and R^ are as hereinbefore defined) or with the corresponding fortnamide in the presence of formic acid and if necessary subsequently heating the product with a dilute acid.

The reductive amination is preferably carried out at temperatures from 50 to 250°C, optionally in the presence of a solvent and optionally whilst distilling off simultaneously the water formed by the reaction. It is of particular advantage however, to use an excess of the amine of formula III and/or the formic acid which excess serves as solvent. If a compound of formula III wherein and/or R^ represents a hydrogen atom is used, the reaction mixture obtained must be refluxed after the reaction with a dilute acid, e.g. 2N hydrochloric acid. j) For the preparation of compounds of general formula I (wherein R^, R^ and R,. are as hereinbefore defined, R^ represents a hydrogen atom and R^ is as H (III) - 19 - 40146 hereinbefore defined with the proviso that it does not represent an acetyl group): Reduction of a compound of formula CH - H R.

(ZZXI) or of a compound of formula 10 (Xllla) (wherein R^, R^and R^ are as hereinbefore defined, R^" is as hereinbefore defined for R^ with the proviso that it does not represent an acetyl group and Z represents a cyclohexylidene group optionally substitued by one or two hydroxy groups, an alkylidene group with 3 to 5 carbon atoms or a morpholinocarbonylmethylidene group).

The reduction is conveniently effected by means of catalytically activated hydrogen (e.g. hydrogen in the presence of Raney nickel or Raney cobalt), nascent hydrogen (e.g. activated metallic aluminium and water, sodium nmalgam and ethanol or zinc and hydrochloric acid) or - 20 - 401 4G 10 advantageously a complex metal hydride (e.g. sodium borohydride), preferably in the presence of an appropriate solvent, for example 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 from -50 to 100"C.

The compound of formula XIII or formula Xllla may be conveniently prepared jji situ and reduced without previous isolation. k) For the preparation of compounds of general formula I as hereinbefore defined with the proviso that does not represent a 1-hydroxymethyl group: Reaction of a compound of formula ch2oh (xiv) (wherein Rj and R2 are as hereinbefore defined and R^"* 15 is as hereinbefore defined for R3 with the proviso that it does not represent the 1-hydroxymethyl group) with a compound of formula 0 «= P V" r5'» (xv) - 21 - 4 0116 (wherein R^''' represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms and R^'" represents an alkyl group containing 1 to 3 carbon atoms or a cyclohexyl group, or R^"' and R^'" together with the nitrogen atom to which they are attached represent a morpholino or piperidino group) or with a compound of formula rg - co - nct <xv») R5 (wherein R, and R, are as hereinbefore defined and R„ 4 5 o represents an alkyl, aryl or aralkyl group.

The reaction is conveniently carried out in the presence of a solvent such as tetralln and at temperatures from 100 to 250°C, preferably, however, from 120 to 180°C. Hie reaction may, if desired, be performed in the absence of a solvent. 1) For the preparation of compounds of general formula - 22 - 4 0116 Reaction of a compound of formula (XVI) (wherein R2 and are as hereinbefore defined and Rg represents a hydrogen atom or an alkyl, aryl, aralkyl or hydroxy group) with a compound of formula (wherein R^ and R^ are as hereinbefore defined) and, if necessary, the subsequent hydrolysis of the product formed.

The group Rg in the compound of formula XVI may for example be a methyl, ethyl or phenyl group.

The reaction is conveniently carried out in the presence of a solvent such as tetralln or in an excess of the amine of formula III used, and preferably at temperatures from 100 to 200°C, preferably, however, at temperatures from 120 to 180°C. The reaction may, H (III) - 23 - .1 Ollli 10 however, also be performed In the absence of a solvent.

The subsequent hydrolysis Is preferably carried out In the presence of an acid such as hydrochloric acid or sulfuric acid or In the presence of a base such as sodium hydroxide solution, and in the presence of a polar solvent, e.g. water, ethanol/water or dloxane/ water. The hydrolysis is conveniently effected at temperatures up to the boiling point of the solvent used. m) For the preparation of compounds of general formula I as hereinbefore defined wherein R^ represents a carbalkoxy group: Reaction of a compound of formula (XVII) (wherein R., R_, R. and Rc are as hereinbefore defined 12 4 5 and B represents a carboxyl group or a functional derivative thereof) with a compound of formula 10 (XVIII) - 24 - 4 0116 (wherein R^q represents a lower alkyl group and C represents a hydroxy group or a halogen atom).

The group B in the compound of formula XVII may for example be an anhydride, acid hallde, amide, 5 amidine, ester or nitrile group.

The reaction is conveniently performed in the presence of a solvent (e.g. ethanol, tctrahydrofuran or dioxane) or in an excess of the compound of formula XVIII used and is preferably effected at temperatures 10 from 0 to 100°C, most preferably at the boiling point of the solvent used. The reaction may if desired be effected in the presence of an alcoholate such as sodium ethoxide in which case the intermediate imino csLer which forms is subsequently hydrolysed with 15 water. The reaction may also if desired be effected in the presence of an acid such as ethanolic hydrochloric acid whereby the compound of formula I produced is deacylated.

Compounds of general formula 1 as hereinbefore defined wherein represents a carbamoyl group may be prepared by partially hydrolysing the corresponding compound of formula 1 wherein R^ represents a cyano 20 - 25 - 4 0110 group. Compounds of general formula I (wherein R^ represents an aliphatic or optionally substituted aromatic acyl group and to Rj are as hereinbefore defined with the proviso that they do not represent 5 groups containing reactive hydrogen atoms) may be prepared by acylating the corresponding compound of formula I wherein R^ represents a hydrogen atom with an appropriate acylating agent. Suitable acylating agents include for example acyl halides, symmetrical 1° acid anhydrides and mixed acid anhydrides. The reaction is advantageously effected in the presence of a dehydrating agent such as N,N*-dicyclohexyl-carbodiimide.

The compounds of general formula I as hereinbefore 1*» defined may if desired be subsequently converted into their acid addition salts, for example their physiologically compatible acid addition salts, by reaction with an appropriate acid. Hydrochloric acid, hydro-bromic acid, sulfuric acid, phosphoric acid, lactic 2^ acid, citric acid, tartaric acid, maleic acid or fumaric acid have proved suitable for this purpose. One, two or three moles of acid per mole of the - 26 - 4 014 6 compound of formula I may be used.

Compounds of general formula(II used as starting materials may be prepared according to known processes, e.g. by reaction of the corresponding toluene derivative "i with N-bromo-succinimide or with halogen under UV Irradiation, by reaction of the corresponding benzyl alcohol with thionyl chloride, by reaction of the corresponding benzyl halide with an alkali metal salt of a carboxylic acid or alkali metal alcoholate or 10 phenolate, or by halogenation of the corresponding benzyl ammonium salt.

The benzylamlnes of general formulae IV, V, VI and VII may for example be obtained by reaction of the corresponding benzyl halides with the corresponding 1 r> amines.

The benzamides of general formula VIII may, for example, be obtained from the corresponding isatoic acid anhydrides by reaction with the corresponding amines1.

Compounds of general formulaeII, IX, X and XVII 20 used as starting materials may be obtained, for example, by reaction of the corresponding benzyl halide with the corresponding amine. The starting - 27- 401 40 compounds of genernl formula X nay also be obtained by reaction of the corresponding 6H-3,l-benzoxazine with the corresponding amine.

Aldehydes of general formula XII used as starting r> materials may be obtained, for example, by oxidation of the corresponding benzyl alcohol conveniently with manganese dioxide, or by hydrolysis of the corresponding nitron.

Compound of general formula XIII and Xllla used as 10 starting materials may be obtained, for example,by reaction of the corresponding carbonyl compound with the corresponding amine.

Compounds of general formulae II and XIV used as starting materials may be obtained, for example, by I r> reduction of the corresponding aldehyde or by sapon ification of the corresponding benzyl halide.

Compounds of general formula XVI may be obtained, for example, by halogenation of the corresponding benzoxazine derivative or by dehydration of a 2-acyl-20 amino-benzyl alcohol.

The new compounds of general formula I which have been tested possess valuable pharmacological - 28 - 4 014 6 properties, in particular an anti-ulcus activity, a secretolytic and antitussive effect and a stimulating effect on the production of the surfactant or anti- : atelectasis factor of the alveoli.

Ilic compounds A =» 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzyl- amine-hydrochloride, I) = N-ethyl-2-amino-3-bromo-5-carboxy-N-cyclohexyl- benzylamine-hydrochloride, C. = N-ethyl-2-amino-5-bromo-N-cyclohexyl-3-f luoro- benzylamine-hydrochloride, I) = N- ( 2-ami no- "S-bromo-3-methy 1-benzy 1)-hexame thy 1 - eneamine-dihydrochloride, K = N-(2-amino-5-bromo-A-tert.-butyl-benzyl)-morpholine- dihydrochloride, K = 5-acetyl-2-amino-3-bromo-N,N-dimethyl-benzylamine and G = 2-amino-3-bromo-N,N-dimethyl-5-fluoro-benzylamine-hydrochloride, for example, have been investigated with regard to their biological activities. - 2') - 4 0 1 1 U I . ''i'i'I i'I i»ly( !»• «•< tr> t : 'lht> expectoration tests were carried out on narcotized guinea pigs and narcotized rabbits (see Perry and Boyd, Pharmacol, exp. Therap. 73, 65 (1941)). The substances under test were administered perorally to groups of 6 to 8 animals in a dosage of 8 mg/kg. The increase of secretion within 2 hours of application of the test substances was calculated by comparison of the quantities of fluid secreted.

The circulatory effect of the new compounds according to the invention was determined by intravenous application of 2, 4 and 8 mg/kg of the substance under test to 3 cats under chloralose-urethane narcosis: The results of the tests on guinea pigs and rabbits are given in the following Tables: Tests on guinea pigs: Substance Increase of secretion Circulatory effect A + 90 % 2,4 and 8 mg/kg: no change B ♦ 81 % 2,4 and 8 mg/kg: no change C ♦ 100 % G ♦ 84 % - 30 - | 4 0 1 -J 6 'I'esi »n rabbi Is Substance Increase of secretion D ♦ 72 % E * 77 % F ♦ 75 % 2. Anti-ulcus activity: Hie activity of the* substanccs under test on the formation of ulcers was determined according to the method of K. Takagi et aI (Jap. J. Pharmac. r> ( I'H.O)). 'Ihe abdomen of female rats having n body weight from 220 to 250 was opened under sedation and the stomach was extruded. 0.05 ml of a 5Z acetic acid solution was then injected between muscularis mucosae and submucosa of the stomach. Ihe alxlonim 10 was closed again after injection. The ulcers formed in the mucosa after 1 to 5 days were treated for three weeks by admixing ihe lest substances with the animal's food in dosages of 50 and 100 mg/kg (6 animals/dosc) . Ihe control animals were fed with untreated but 15 otherwise similar powdered food. - 31 - 40146 After treatment for three weeks the animals were killed, the stomach removed and the ulcers were measured (length and breadth). The activity of the substances under test was estimated by comparison of S the sizes of the ulcers of the treated animals with those of the control group. (100%).

A dosage of 50 mg/kg of substance A was administered perorally effected a 52% reduction of the ulcers and a dosage of 100 mg/kg effected a 79% reduction of the 10 ulcers. 3. Acute toxicity: The acute toxicity of the substances under test was determined by administration of a single dose of 1,000 or 2,000 mg/kg p.o. of the test substance to groups of 15 5 white mice.

Substance Acute toxicity A >2 000 mg/kg p.o. (0 out of 5 animals died) B > 1 000 mg/kg p.o. (0 out of 5 animals died) C >1 000 mg/kg p.o. (0 ouc of 5 animals died) D >1 000 mg/kg p.o. (0 out of 5 animals died) E ) 1 000 mg/kg p.o. (0 out of 5 animals died) F 000 mg/kg p.o. (2 out of 5 animals died) G >1 000 mg/kg p.o. (0 out of 5 animals died) - 32 - 40146 According to a still yet further feature of the present invention there are provided pharmaceutical compositions comprising as active Ingredient at least one compound of formula 1 as hereinbefore defined or a 5 physiologically compatible acid addition salt thereof in association with a pharmaceutical carrier or rxcipient. The compositions may if desired additionally contain a further active ingredient.

The compositions according to the invention may 10 for example be adapted for oral, rectal or parenteral administration. Suitable forms of administration include for example, syrups, drop solutions, tablets, coated tablets, capsules, powders, ampoules and suppositories formulated with conventional carriers I r, or excipients.

The compositions according to the invention may advnntngcously be administered in the form of dosage units, each dosage unit containing from 1 to 100 ing, preferably from 4 to 60 mg, of active ingredient 7(> according to the invention. The daily dose generally contains from 2 to 300 mg, preferably 4 to 200 mg, of active ingredient. Compositions administered for - 33 - 40146 their secretolytic activity generally contain from 1 to 20 mg, preferably 4 to 15 mg, of active ingredient in a single dosage unit. Compositions administered for their anti-ulcus activity generally contain from 25 to 100 mg, preferably 30 to 60 mg of active ingredient in a single dose.

The following Examples serve to illustrate the preparation of the new compounds according to the invention and of pharmaceutical compositions containing the same:- - 34 - 40146 ExampIc I 2-Amino- 3- bronvo-N ,N-dlmethy I- 5- f luoro-benzy 1amine r>. r) g of 2-nmino-3-bromo-5-fluoro-benzy I .-ilcohol were dissolved in 150 ml of chloroform. Whilst sLirring and cooling with ice, 7.13 g (A. 35 ml) of thionyl chloride were added dropwise, whereby a yellow precipitate separated out. The suspension was allowed to rest overnight, evaporated to dryness in vacuo by means of a rotation evaporator at room temperature. The crude benzyl chloridc thus obtained was suspended in 100 ml of chloroform.

Whilst stirring and cooling with ice 20 ml of dimethyl-,-imine were added, whereby a clear solution was obtained. The solution was allowed to stand for 30 minutes under ice-cooling and was extracted twice with saturated potassium carbonate solution. The chloroform phase was washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The residue was taken up in absolute ethanol and acidified with ethereal hydrochloric acid to pH 5. The precipitated hydrochloride was sucked off and dissolved in .ibsolute ethanol. After addition of charcoal Lhi- solution was heated to boiling. 4014G After filtering off the charcoal and addition of ehter, colourless crystals were obtained.

Melting point: 241 - 243"C.

Example 2 1 2-Acetylamlno-N ,N-diethyl-3-methyl-benzylamine 20 g of diethylamine were added to 22 g of 2-acetylamino-3-methyl-benzyl bromide in 1.6 1 of carbon tetrachloride and the mixture was refluxed for I hour. Subsequently, the reaction solution was evaporated, lo the residue dissolved in I I. of 2 N hydrochloric ncid, extracted twice with chloroform, the acid phase was made alkaline with concentrated ammonia and extracted three times with chloroform. T'.ie organic phase was evaporated and the residue chromatographed over silica gel with I r> acetone-methanol (9 : 1). The crude product obtained was dissolved in ethanol, acidified with ethanolic tartaric acid and 2-acetylamino-N,N-diethyl-3-methyl-benzylamine was crystallized as its tartrate salt on addition of ether. 20 M.p. 134 - 136"C. - 36 - 4 0 1 -J 6 Kxnmple 3 2-AceLy lamlno-5-bromo-N,N-diethy 1'- 1-diethy lamlnomethy 1 - benzy lamlne 21* g of diethy Iamine were added to 16. r> g of 2-rt acetylamino-5-bromo-3-bromoraethy 1-benzy 1 bromide Lu 1.6 1 of carbon tetrachloride and the mixture was refluxed for I hour. Subsequently, the reaction solution was evaporated, the residue dissolved in 0.7 l. of 2 N hydrochloric acid and extracted twice with chloroform. |o The hydrochloric acid phase was made alkaline with conccntraLed ammonia and extracted three times with chloroform. The organic phase was dried with sodium sulfate and the solvent was distilled off. The residue was separated by column chromatography over silica gel with I r> ethyl acetate-methanol (I : 1). The corresponding fractions were united and 2-acetylamino-5-bromo-N,N-dLethy1- 3-diethylaminomethy1-benzy1amine was obtained by recrysta11ization from petroleum ether.

M.p. 01. r> - 93' C.

Kxamp1e 4 2-AcetyI amino-5-bromo-A-tert.-bulyl-N-cyclohcxyI-N-mel.hyI -l>en/.y I amine 2<> - 57 - 0146 25 g qf 2-acetylamino-5-bromo-4-tert.-butyl-benzyl bromide were refluxed in 1.5 1. of carbon tetrachloride with 23 g of N-methyl-cyclohexylamine for 1 hour. After cooling the precipitated N-methylcyclohexylamine hydro-bromide was filtered off and the filtrate evaporated. The residue was admixed with 2 N hydrochloric acid and extracted twice with benzene. The acid phase was made alkaline with concentrated ammonia and extracted three times with chloroform, and the organic phase was dried and evaporated. The residue was purified by column chromatography over silica gel with ethyl acetate-chloroform (1:1) and 2-acetylamino-5-broino-4- tert.-butyl-N-cyclohexyl-N-methy1-benzylamine hydrochloride was precipitated from a solution in ethanol-ether with ethanolic hydrochloric acid. The crude product was recrysLalIized from ethanol-ether.

M.p. 2'i I - 2 WC.

Example 2-Acetylamino-4-tert.-buty1-5-chloro-N-cyclohexy1-N-methyl-benzylamine - 38 - 40146 26 g of N-methyl-cyclohexylamine were added to 29 g of 2-acetylamino-4-terL.-butyl-5-chloro-benzyl bromide in 1.5 i. of carbon tetrachloride and refluxed for 2 hours. After cooling, the N-methyi-cyclohexylamine hydrobromide was filtered off and the filtrate evaporated. The residue was taken up in 2 N acetic acid and extracted with chloroform. The acid phase was made .ilk a lino with concentrated amnonia and extracted three times with chloroform and the organic phase was separated and evaporated. After column chromatographic purification over silica gel with ethyl acetate-chloroform (1 : 1), 2-acety1amino-4-tert.-buty1-5-chloro-N-cyclohexy1-N-methy1-benzylamine crystallized from absolute ethanol and was recryslallized from ethanol.

M.p. 174 - 175-5 C.

Examp1e 6 2-Acetylamino-5-tert.-butyl-N-cyclohexyl-N-methy1-benzyl-amine 24 £ of N-methy l-cyclohexy Limine were added to 2 1 y, of 2-ac rly I ami no-r>-lcrl.-buty 1 -ben/.y I bromide in I. f> I. - <•) - 40146 of carbon tetrachloride and the mixture was r»M luxed for 1 hour. After cooling the N-methyl-cyclohexylamine hydrobromide was filtered off, the filtrate was evaporated and the crude product was purified chromatographlcally 5 over silica gel with ethyl acetate. The corresponding fractions were evaporated and 2-acetylamino-5-tert.-buty1-N-cyclohexyl-N-methy1-benzylamine was recrystallized from petroleum ether.

M.p. Ill - 112.5°C. l<> Example 7 4-Acetylamino-3-tert.-butyl-N-cyclohexyl-N-methy1-benzylamine 48 g of N-methyl-cyclohexylamine were added to 56 g of 4-acetylamino-3-tert.-buty1-benzyl bromide in 15 500 ml of chloroform and the mixture was refluxed for 1.5 hours. The mixture was subsequently extracted three times with water and the organic phase was evaporated. The residue was purified column chromatographlcally over silica gel with chloroform-methanol (5 : 1) and the 20 4-acetylamino-3-tert.-butyl-N-cyclohexyl-N-methy1- benzylamine hydrochloride was crystallized from absolute - 40 - I 4 0 1 4 6 ethanol-ether under addition of absolute ethanolic hydrochloric acid. i M.p. 240 - 243"C. (decomp.).

Example 8 5-AcctyI-2-acetylamino-N,N-dimethy1-benzylamine H.I g of dimethylamine were added to 21 n of Vacclyl-2-acetylamino-benzyl bromide in 500 ml of chloroform and the mixture was stirred for 30 minutes.

When the exothermic reaction began the solid material dissolved. Subsequently, the reaction solution was shaken out three times with water and twice with 2 N hydrochloric acid. The hydrochloric acid phase was extracted with chloroform, made alkaline wilh 2 N amnion in and then again extracLed twice with chloroform. The organic phase was evaporated, the residue purified column chromatographically over silica gel with ethyl acetate and the corresponding fractions were combined and evaporated to dryness, whereby 5-acety1-2-acetylamino-N.N-dimethyl-benzylamine was obtained in crystal form. M.p. bH - 72C.

Example *> 146 2-Amino-.>-brorao-N-cyclohexyl-5-f luoro-N-methy 1-benzy lamine 3 g of 2-amino-N-cyclohexyl-5-fluo^o-N-methyl-benzy lamine were dissolved in 30 ml of glacial acetic acid Whilst stirring, a solution of 1.98 g (0.63 ml) of bromine in 20 ml of glacial acetic acid was added dropwise at room temperature. When the addition had been completed, stirring was continued for 10 minutes and, subsequently, whilst ice-cooling 10 N hydroxide solution was added until a pH of 9 was reached. The mixture was then extracted twice with 150 ml portions of methylene chloride The united methylene chloride solutions were washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The residue was dissolved in absolute ethanol nnd acidified with ethanolic hydrochloric acid to pH 3. The precipitated hydrochloride was sucked off and recrystallized from a mixture of absolute ethanol and ether.

M.p. 222 - 224°C.

Example 10 2-Amino-3-bromo-5-tert.-butyl-N-cyclohexyl-N-methy1-benzylamine - 42 - 40146 I 10 g of 2-amino-5-tert.-butyl-N-cyclohexyl-N-methyl-benzylmnine were dissolved in SO ml of 90% acetic acid and 5.8 g of bromine were added dropwise at room temperature. Subsequently, the reaction solution was 5 stirred for 10 minutes. It was then diluted with 200 ml of water, made alkaline with concentrated amnonia and extracted three times with chloroform.

The organic phase was evaporated, the residue purified column chromatographlcally over silica gel with 10 chloroform/ethyl-acetate (5:1) and the 2-amino-'J- bromo-5-tert.-butyl-N-cyclohexyl-N-methyl-benzylamine hydrochloride crystallized out from ethanol-ether on addition of ethanolic hydrochloric acid.

M.p. 214 - 215°C (decomp.). 1 r> Example 11 5-Acetyl-2-amino-3-bromo-N,N-dimethy1-benzylamine 0.0 g of bromine were added dropwise to 12.8 g of 5-acety1-2-amino-N,N-dimethy1-benzy Limine hydrochloride dissolved in 100 ml of 80% acetic acid. Subsequently, 20 the reaction mixture was made alkaline with 2 N ammonia, extracted twice with chloroform and the organic phase - 4} - 4 0116 was evaporated. The residue was recrystallized from ethanol-water, and 5-acetyl-2-amino-3-bromo-N,N-dimethyl-benzylamine of m.p- 92 - 95°C was obtained.

Example 12 2-Amino-5-chloro-N-cyclohexyl-N-methyl-3-trif luoromethyl- benzylamine A solution of 9.5 g of 2-amino-N-cyclohexyl-N-methyl-3-trifluoromethyl-benzylamine and 3 ml of pyridine in AO ml of tetrahydrofuran was cooled to -10"C and whilst stirring at this temperature it was mixed over 20 minutes with a solution of 9.1 g of iodosobenzene dichloride in 80 ml of tetrahydrofuran. After stirring for A.5 hours at 0°C to -10°C, the mixture was nlLowed Lo sl;tn<l for 18 hours .-it 20"C. The reaction mixlurc was diluted with water and extracted with chloroform. The organic phase was washed with aqueous potassium carbonate nnd water. After drying over magnesium sulfate, the solution was evaporated vacuo. The oily residue was taken up in ethyl acetate and the hydrochloride of the title compound was precipitated with isopropanolic hydrochloric acid. After recrystallization three times - AA - 40146 from eLhanol using charcoal, colourless crystals were* obtained.

M.p. 260 - 262°C.

Example 1.3 2-Amino-N,N-diethy1-3-methy1-benzylamine H g of 2-acetylamino-N,N-diethyl-3-methy1-benzy1-aminc were dissolved in 100 ml of 2 N hydrochloric acid, refluxcd for 14 hours and the solution was decolorised with charcoal and made alkaline with concentratcd ammonia. The mixture was extracted three times with chloroform. The organic phase was evaporated anil the residue was purified column chromatographicaIly over silica gel with ethyl acetate. The crude base was dissolved in acetone-ethanol and neutralized with ethanolic hydrochloric acid, whereby 2-amino-N,N-diethy1-3-methy1-benzylnmine hydrochloride crystallized out.

M.p.: 182 - 184'C.

Examp1e 14 2-Amino- r>-bromo-N ,N-diethy 1- 3-diethy laminomethy 1-benzy lamine 11.5 g of 2-acetylamino-5-bromo-N,N-diethy I -1-diethylaminomethy1-benzylamine were dissolved in 250 ml 40146 of 2 N hydrochloric acid nnd the mixture was rofluxed for 14 hours and then decolorised with charcoal. The filtrate was made alkaline with concentrated ammonia, extracted three times with chloroform and the organic phase was evaporated. The residue was purified column chromatographlcally over silica gel with chloroform-ethyl acetate (1 : 2). The corresponding fractions were combined and evaporated and the residue was dissolved In absolute ethanol nnd weakly acidified with absolute ethnnolic hydrochloric acid, whereby 2-amino-5-bromo-N,N-diethy1-3-diethylaminomethy1-benzylamine crystal 11zed out as the hydrochloride.

M.p. 213.5 - 215°C.

Example 15 2-Amino-5-bromo-4-tert.-butyl-N-cyclohexyl-N-methy1-benzylamine 5 g of 2-ncetylamino-5-bromo-4-tert.-buty1-N-cyc lohrxy I-N-methy I-ben/.y lamine were refluxed in 50 ml of ethanol and 50 ml of concentrated hydrochloric acid for 15 hours. The mixture was made alkaline with concentrated ammonia and was extracted three times - 46 - 4 014 6 with chloroform. The organic phnse was evaporated, the residue purified column chromatographically over silica gel with ethyl acetate, and 2-amino-5-bromo-4-tert.-buty1-N-cyclohexy1-N-methy1-benzy Limine crystal 1ized as the hydrochloride from an ethanol-ether solution on the addition of ethanolic hydrochloric acid.

M.p. 202 - 202.5"C (decomp.).

Example 16 2-Amino-5-tert.-butyl-N-cyclohexyl-N-methy1-benzylamine 15 g of 2-acetylamino-5-tert.-butyl-N-cyclohexyl-N-methy lbenzy lamine were refluxed in 0.5 1. of 4 N hydrochloric acid for 14 hours. Subsequently, the solution was made alkaline with concentrated anmonia, extracted three times with chloroform avid the organic phase was evaporated. The crude product was purified column chromatographically over silica gel with ethyl acetate, and 2-amino- 5-tert. -butyl-N-cyclohexyl-N-methy 1-ben/.y 1 -amine crystallized out as the hydrochloride from anncetone-ether solution by addition of ethanolic hydrochloric acid.

M.p. 144 - 146°C. - 47 - 40146 Example 17 4-Amino-3-tert. -buty 1-N-cyclohexy 1-N-methy 1-benzy lamine 20 g of 4-acetylamino-3-tert.-butyl-N-cyclohexyl-N-methyl benzylamine were added to 200 ml of 3 N r> hydrochloric acid and the mixture was refluxed for b hours nnd then made alkaline with concentrated nmroonin. The mixture was extracted three times with chloroform nnd the organic phase was evaporated. After addition of absoluLe ethanolic hydrochloric acid, 4-amino-3-tert.~ 10 buty1-N-cyclohexy1-N-methy1-benzylamine crystallized out as the dihydrochloride from an absolute ethnnol-eLher solution.

M.p. 107 - 199"C (decomp.).

Example 18 15 5- Acetyl- 2-amino-N ,N-dimethy 1-benzy lamine 22.5 g of 5-acetyl-2-acetylamino-N,N-dimethyl-benzylamine were dissolved in a solution of 8 g of sodium hydroxide in 400 ml of 50% ethanol and the mixture was heated at 70 - 80°C for 5 hours. Subsequently, the 20 reaction solution was diluted with water, extracted three times with chloroform and the organic phase was evaporated. The residue was dissolved in absolute ethanol - 48 - I 40146 nnd neutralized with absolute ethanolic hydrochloric 5 acid, whereupon the 5-acetyl-2-nmino-N,N-dimethy1-benzylamine hydrochloride crystallized out.

M.p. 20') - 21^"C (decomp.).

ExampIc 10 N-[ 2-Aini no- >-bromo- V ( I -hydroxy-cthy I)-benzy 1 "}-hexa-methyIcncamine g of N-( r>-acoly l-2-ainino- l-l>romo-bcnzy I )-hexa-methy Icncamine were dissolved in 250 ml of ethanol and H>() ml of water, and 6 g of sodium borohydride were ndded In portions whilst stirring. The mixture was «*i I lowed to stand for I r> hours and was then diluted with H)<) ml of water and extracted three times with chloroform. The organic phase was extracted with water and evaporated. The residue was purified column chromatographically over silica gel with ethyl acetatc, whereby the N-[2-amino-5-bromo-5-(l-hydroxyethyl)-benzyll~hexamethyleneamine was obtained in crystalline form and was recrystallized from isopropanol.

M.p. 1 J<> - 112"C. - 49 - 40146 Example 20 N-Ethy l-2-nmlno-3-bromo-5-carboxy-N-cyclohexyl-benzylnmine 13 g of N-ethyl-2-amino-3-bromo-5-carbethoxy-N-cyclohexy1-benzylamine were boiled with 100 ml of 6 N hydrochloric acid for 1 hour. Subsequently, the solution was decanted from the oily residue produced and the solution was evaporated to dryness. The residue was recrystallized from methanol. N-Ethyl-2-amino-3-bromo-5-carboxy-N-cyclohexy 1-benzy lamine hydrochloride of m.p. 227 - 229 C was obtained.

Examp1e 21 2-Amino-3-bromo-5-carbamoyl-N,N-diethy1-benzylamine 11 g of 2-amino-5-bromo-5-cyano-N,N-diethy1-benzylamine were refluxed with 70 ml of ethanol and 100 ml of 5 N sodium hydroxide solution. After cooling the mixture was diluted with 100 ml of water and extracted with chloroform. The chloroform extract was dried over sodium sulfate, evaporated and the residue was recryslallized from isopropanol. 2-Amino-3-bromo-5-carbamoy1-N,N-diethy1-benzylamine of m.p. 140 - 142 C was obtained. - 50 - 401JU Example 22 2-Acetamlno-3t-bromo-5-carbethoxy-N.N-dlethy 1-benzy lamine 1 g of 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine was dissolved in 2 ml of acetyl chloride and heated to 50°C for 1 hour. The excess of acetyl chloride was evaporated in vacuo and the residue was distributed between cold dilute ammonia and chloroform. The chloroform solution was evaporated and the product was purified by chromatography on silica gel (eluent : ethyl acetate). The evaporation residue of the cluate was dissolved in isopropanol and 2-acetamino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine hydrochloride was crystallized by addition of isopropanolic hydrochloric acid and ether.

M.p. 190 - 194°C.

Example 23 2-Acetamlno-3-bromo-N,N-diethy1-5-methy1-benzy1amine 1.53 g of 2-amino-3-bromo-N,N-diethyl-5-methyl-benzylnmine hydrochloride were dissolved in 50 ml of acetic nnhydride at 75nC. The mixture was evaporated to dryness Jjn vacuo and the residue was recrystn1lized - 51 - 40146 from ethanol. The 2-acetamino-3-bromo-N,N-diethy1 -5-methy1-benzylamine hydrochloride obtained melted at 170 - 172"C.

Example 24 5 2-Acetamino-3-bromo-N>5-dimethyl-N-(trans-4-hydroxycyclo- hexy1)-benzylamine 2.2 g of 2-amino-3-bromo-N,5-dimethyl-N-(trans-4-hydroxycyclohexyl)-benzylamine were dissolved in 100 ml of methanol nnd heated to boiling. In the course of 10 2 hours 75 ml of acetic anhydride were added and the methyl acetate thereby produced was distilled off. The mixture was evaporated to dryness in_ vacuo and after addition of further methanol it was evaporated again. The obtained residue wm. dissolved in ethanol and I r> converted into 2-acetamino-3-bromo-N,5-dimethyl-N- (trans-4-hydroxycyclohexyl)-benzylamine hydrochloride with eLhanolic hydrochloric acid.

M.p. 246 - 248"C.

Example 25 20 2-Acetnmino-5-carbethoxy-N,N-diethy1-benzylamine - r> 2 - 40146 JO g of 2-acetamino-5-carbethoxy-benzyl bromide dissolved in 400 ml of chloroform and 100 ml of ethanol were added to 22 g of diethylamine and the mixture was refluxed for 1 hour. It was cooled and then evaporated in vacuo. The residue obtained was distributed between dilute ammonia and chloroform, the chloroform solution was dried over sodium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica j^l (elueiil : ethyl ncclatc). The obtained 2-acctamino-r>-carbcthoxy-N,N-diethy 1-benzy lamine was recrystal lized from ethanol.

M.p. 57 - 50 C.

Kxample 2(> 2-Amino-N-cyclohexy1-N-methy1-3-trifluoromethy1-benzylamine 20 f» of 2-amino-3-trifluoromethy 1-benzy 1 alcohol were dissolved in 200 ml of chloroform and whilsl stirring 15.9 ml of thionyl chloride was added dropwise over 10 minutes. The mixture was then refluxed for 90 minutes. It was cooled and all volatile matter was carefully removed iji vacuo. The obtained residue of the crude benzyl chloride was dissolved in 200 ml of chloroform. - 53 - 146 Whilst stirring mechanically and Ice-cooling, 38.1 g of N-methyl-cyclohexylamine were added over 10 minutes and ofterwnrds the mixture was left to stand for IB hours at 20"C. The mixture was washed with saturated potassium carbonate solution, dried and the solvent was removed in vacuo. The oily evaporation residue was purified by chromatography over a silica gel column (mobile phase : chloroform: methanol =9 : 1). The obtained evaporation residue, which was again an oil, was dissolved in a mixture of ether and ethyl acetate (1:1). On addition of isopropanolic hydrochloric acid, the 2-.imino-N-cyc lohexy 1-N-methy 1-3-trifluoromethy 1-benzy Limine hydrochloride crystallized. After re-cryst.illizing twice from isopropanol, the melting point was 203 - 206°C.

ExampIc 27 2-Amlno-3-bromo-5-carbethoxy-N,N-dicthy1-benzy Limine HO g of 2-amino-5-carbethoxy-N,N-diethy1-benzylamine were dissolved in 300 ml of glacial acetic acid and 30 ml of water and 40 g of bromine in 40 ml of glacial acetic acid were added dropwise whilst stirring at room - 54 - 40146 temperature. The mixture was left to stand for I hour, poured on to ice, made alkaline with anmonia and extracted with chloroform. The united chloroform solutions were evaporated to dryness in vacuo. The obtained crude product was purified by chromatography on silica gel (eluation agent: ethyl acetate) and converted with isopropanolic hydrochloric acid into 2-amino-}-bromo-5-carbcthoxy-N,N-diethy1-benzylamine hydrochloride, which was rocrysta11ized rrom ethanol.

M.p. I(>r» - 168 C..

Example 2H 2-Amino- l-bromo-5-cyano-N-cyclohexy1-N-methy1-benzylamin^ 7 g of 2-amino-5-cyano-N-cyclohexyl-N-methyl-benzylamine were dissolved in 100 ml of 90% acetic acid and whilst stirring a solution of 4 g of bromine in 4 ml of glacial acetic acid was added dropwise. The mixture was stirred for 1 hour at room temperature and then for a further M) minutes at 60 C, cooled off, poured onto ice, made alkaline with ammonia and extracted three times with chloroform. The chloroform solution was evaporated j_n vacuo, the residue was dissolved in ethanol - 55 - 146 nnd on addition of ethanolic hydrochloric acid 2-nmino- 1-bromo-5-cynno-N-cyclohexy 1-N-methy 1-benzy lamine hydrochloride crystallized.

M.p. 2 lb - 2MVC.

Example 20 2-Amino-r>-chloro-N-cyclohexyl-3-methoxy-N-methy 1-benzy Inmine I I g of 2-amino-N-cyclohexyl-3-methoxy-N-methy1- benzylamine were dissolved in 100 ml of glacial acetic acid and whilst stirring a solution of 2.8 g of chlorine in r>0 nil of glacial acetic acid was quickly added at room temperature. When the addition was complete the mixture was immediately poured into a sodium hydrogen sulfite solution, mixed with ice and made alkaline with 10 N sodium hydroxide solution. The precipitate was extracted with chloroform^ the chloroform phase was washed with water, dried over sodium sulfate and evaporated to dryness jji vacuo. The residue was chromatographed over silica gel with chloroform/ethyl-acetate O : 1). The crude product thereby obtained was dissolved In absolute ethanol and acidified with ethereal hydrochloric acid to pH 5-6 and mixed with petroleum ether. The - 56 - 40146 precipitated hydrochloride was sucked off and washed with a small ^quantity of petroleum ether.

M.p. IH9 - 193°C (decomp.).

Example 30 2-Amino-5-bromo-N-cyclohexy1-N-methy1-3-trifluoromethy1-benzylamine 9.5 g of 2-amino-N-cyclohexyl-N-methyl-3-tri-fluoromethy1-benzylamine were dissolved in 140 ml of 70% acetic acid and mixed during 5 minutes with 5.5 g of bromine in 30 ml of glacial acetic acid whilst stirring. After 90 minutes the excess of bromine was destroyed with sodium hydrogen sulfite solution and the mixture was then evaporated in vacuo. The residue was distributed between ethyl acetate and saturated potassium carbonate solution. The organic phase was dried and evaporated again Jjn vacuo. The remaining oil was dissolved in a mixture of ether and ethyl acetate (1 : 1) and the hydrochloride of the above-mentioned compound was precipitated on addition of isopropano1ic hydrochloric acid. After recrystnllization twice from ethanol the m.p. was 259 - 261°C. , - 57 - 40146 Example 31 2-Amlno-5-carbethoxy-N,N-dlethy1-benzylamine 19 g of 2-acetamino-5-carbethoxy-N,N-diethyl-benzylamine were dissolved in 100 ml of ethanol and after addition of 60 ml of concentrated hydrochloric acid the mixture was refluxed for 1 hour. The mixture was poured onto ice, made alkaline with ammonia and extracted three Limes with chloroform. The chloroform solution was dried over sodium sulfate, evaporated in vacuo and the crude product was purified by chromatography on silica gel (eluation agent: ethyl acetate). 2-Amino-5-carbethoxy-N,N-dlethy1-benzylamine hydrochloride was obtained by addition of isopropanollc hydrochloric acid and was recrystallized from ethanol.

M.p. 138 - 142°C.

Example 32 2-Ami no- 5-carboxy-N-cyclohexy1-N-methyl-benzylamine A mixture of 21 g of 2-acetamino-5-carbethoxy-N-cyclohexy1-N-methyl-benzylamine in 100 ml of ethanol, 90 ml of water and 60 ml of concentrated hydrochloric acid was refluxed for 1 hour. The mixture was cooled, - 58 - 40146 poured onto ice, made alkaline with ammonia and extracted three times with chloroform. The ammoniacal phase was evaporated to dryness in vacuo and the residue was stirred intimately with ethanol and filtered, 'i The filtrate was evaporated to dryness jhi vacuo, and the residue recrystal1ized from ethanol. 2-Amino-5-carboxy-N-cyclohexy1-N-methy1-benzylamine of m.p. 200 - 20VC was obtained.

Example 33 10 2-Amino-5-carbamoy1-N,N-diethy1-benzylamine A mixture of 10 g of 2-acetamino- 5-cynno-N,N-diethy 1-benzy lamine in 100 ml of "j N sodium hydroxide solution and 70 ml of ethanol was refluxed for 4 hours and was then cooled, diluted with 200 ml of water and 11 extrncted three times with 250 ml portions of chloroform. The chloroform solution was dried over sodium sulfate and evaporated vacuo. The residue was recrystallized from ethnnol. 2-Amino-5-carbamoyl-N,N-diethyl-benzylnminc of m.p. 129 - 131"C. w;is obtained. 2<> Example 34 2-Amino-N-ethy1-N-cyclohexy1-5-meLhy1-benzyInmine - 59 - 40146 A mixture of 2 g of 2-acetamino-N-ethyl-N-cyclohexy1-5-methy1-benzylamine and 50 ml of concentrated hydrochloric acid was heated at 90UC for 1.5 hours. The mixture was cooled, poured onto ice, made alkaline S with sodium hydroxide solution and extracted with chloroform. The chloroform solution was evaporated in vacuo. The residue was dissolved in ethanol and 2-amino-N-ethy1-N-cyclohexyl-5-methy1-benzylamine hydrochloride was obtained on addition of ethanolic 10 hydrochloric acid.

M.p. 189 - 191"C (decomp.).

Example 35 2-Amino- 3-chloro-N-cyclohexyl-5-fluoro-N-methy1 -ben/ylamine 15 A solution of 9.1 g of 2-amino-3-chloro-N- cyclohexy1-5-fluoro-N-methy1-benzamide in 300 ml of absolute ether was added dropwise to a suspension of 3.8 g of lithium aluminium hydride in 200 ml of absolute ether whilst stirring. When the addition 20 had been completed, the mixture was heated for 1 hour at reflux temperature and was then cooled in an ice-bath. - 60 - 40146 The cxcess lithium aluminium hydride was cautiously decomposed with water under nitrogen as protective gas. The organic solution was decanted from the precipitate and dried over sodium sulfate. 2-Ainlno-l-chloro-N-cyclohexy1-5-fluoro-N-methyl-benzylnmine was precipitated ns hydrochloride by acidification with ethereal hydrochloric acid, and was recrystallized from absolute ethanol-ether.

M.p. 190 - 192°C.

Example 36 2-Amino-N-tert.-buty1-5-carbethoxy-benzylamine J.4 g of 2-amino-N-benzy1-N-tert.-butyI-5-cnrbclh-oxy-benzylamine were dissolved in 50 ml of ethanol. Ethanolic hydrochloric acid was added until a pH value of about 2 was reached. The mixture was then hydrogenated in the presence of palladium (10%) on charcoal. After absorption of 1 mol of hydrogen the hydrogenation was interrupted. The solution was separated from the catalyst and evaporated to dryness in vacuo and the residue was distributed between dilute ammonia and chloroform. The chloroform solution was - 61 - 40146 dried nnd evaporated to dryness ond the residue was reerystallized from ethanol, whereby 2-amino-N-tert.-butyl-5-carbethoxy-benzylamine of m.p. 77 - 79"C was obtained. 5 Example 37 2-Acetamino-N-tert.-butyl-5-carbethoxy-benzylamine Melting point: 136 - 139°C.

Prepared from 2-acetamino-5-carbethoxy-benzy1 bromide and tert.-butylamine analogously to Example 2 5. 10 Example 38 2-Amino-N-tert.-butyl-5-carbethoxy-benzylamine Melting point: 77 - 79°C.

Prepared by saponification of 2-ncetnmino-N-terl.-butyI-5-carbethojty-benzyInmine in ethanolic hydrochloric 15 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-20 benzylamine and bromine analogously to Example 27. - 62 - 40146 Example 40 2-Acetamino-5-carbethoxy-N-cyclohexy1-N-methy1-benzylamine Melting point: 71 - 74°C.

Prepared from 2-acetamino-5-carbethoxy-benzy1 bromide and N-methyl-cyclohexylamine analogously to Example 25.

Example 41 2-Amino-5-carbethoxy-N-cyclohexy1-N-methy1-benzylamine Melting point of the hydrochloride: 160 - 170"C. Prepared by saponification of 2-acetamino-5-cnrbethoxy-N-cyclohexy1-N-methy1-benzylamine in ethanolic hydrochloric acid analogously to Example 11. Example 42 2-Amino-1-bromo-5-carbethoxy-N-cyclohexy1-N-methy1-benzylamine Melting point of the hydrochloride: 212 - 215 C. Prepared from 2-amino-5-carbethoxy-N-cyclohexy1-N-methy1-benzylamine and bromine analogously to Example 27.

Example 41 - 63 - 40146 2-Amlno-5-carbethoxy-3-chloro-N-cyclohexyl-N-methy1-benzylamine Melting point of the hydrochloride; 207 - 209"C. Prepared from 2-amino-5-carbethoxy-N-cyclohexy1-r> N-methy 1-benzy lamine and chlorine analogously to Example 27.

Example 44 2-Acetamlno-3-bromo-5-carbethoxy-N-cyclohexy1-N-methy1-benzyInmine 10 Melting point: 220 - 22J'(".

Prepared from 2-amino-3-bromo-5-carbethoxy-N-cyclohexy1-N-methyl-benzylamine and acetyl chloride analogously to Example 22.

Example 45 I r> 2-Acetamino-N-ethy 1-5-carbethoxy-N-cyclohexyl-benzy lamine Melting point: 92 - 95°C.

Prepared from 2-acetamino-5-carbethoxy-benzy1 bromide nnd N-ethyl-cyclohexylamine analogously to Example 2 5. 20 Example 46 - 64 - 40146 N-Ethy1-2-amino-5-carbethoxy-N-cyclohexy1-benzy1 am lne Melting point of the dihydrochloride: 188 - 194"C. Prepared by saponification of 2-acetamino-N-ethyl-5-carbethoxy-N-cyclohexyl-benzylamine in ethanolic r> hydrochloric acid analogously to Example 31.

Example 47 N-Ethy 1-2-amino-3-bromo-5-carbethoxy-N-cyc lohexy 1-benzylamine Melting point: 66 - 68°C. 10 Prepared from N-ethyl-2-amino-5-carbethoxy-N- cyclohexyl-benzylaminc and bromine analogously to ExampIe 27.

Examp1e 48 N-Ethy1-2-amino-5-carbethoxy-3-chloro-N-cyclohexy1-ben/.y lamine Melting point of the hydrochloride: 16r> - I70"C. Prepared from N-ethyl-2-amino-r>-carbethoxy-N-cyclohexy1-benzylamine and chlorine analogously to Example 27.

Examp1e 49 - 65 - lr> 20 146 N-(2-Acetamlno-5-carbethoxy-benzyl)-hexamethyleneamine Melting point: 100 - 102"C.

Prepared from 2-ncetamino-5-carbethoxy-benzyI bromide and hexamethyleneamine annlogously to Example 2 Example r>0 2-Amino-N- tert. - buty l-r>- carbamoyl-benzy lamine Melting point of the hydrochloride: 120 - 130"C. Prepared by saponification of 2-acetamino-N-tert.-butyI-5-cyano-benzylamine in sodium hydroxide solution analogously to Example 3'J.

Examp I e r> 1 2-Amino-3-bromo-N-tert.-butyl-5-carbamoy1-benzylamine Melting point of the hydrochloride: 160 - 170"C. Prepared by saponification of 2-amino-3-bromo-N-tert.-butyl-5-cyano-benzylamine in sodium hydroxide solution analogously to Example 21.

Example 52 2-Amino-5-carbamoy1-N-cyclohexy1-N-methy1-benzyInmine Melting point: 142 - 143"C.

Prepared by saponification of 2-amino- r>-cynno-N-cyclohexyL-N-methyl-benzylamine in sodium hydroxide solution analogously to Example 21. - 66 - 4 0 110 Example 53 2-Amino-3-bromo-5-carbamoy1-N-cyclohexy1-N-methy1-benzyInmine Melting point: 150 - 152"C.

Prepared by saponification of 2-amino-3-bromo-5-cynno-N-cyclohexyl-N-methyl-benzylamine in sodium hydroxide solulion analogously to Example 21.

ExnmpIe 14 2-Acetamino-3-bromo-5-carbamoyl-N-cyclohexy1-N-methy1-benzylamine Melting point: 185 - 190"C.

Prepared from 2-amino-3-bromo-5-carbnmoyl-N-cyclohexy l-N-methy 1-benzy lamine and acetyl chloride analogously to Example 22.

Example 11 N-EthyI-2-amino-1-carbamoyl-N-cyclohexyl-benzyInmine Melting point: 136 - 1 {8"C.

Prepared by saponification of N-ethy1-2-acetamino-5-cynno-N-cyclohexyl-benzylamine in sodium hydroxide solution analogously lo Example 33. - 67 - 40146 Example 56 N-Ethyl-2-amlno-3-bromo-5-carbamoy1-N-cyclohexy1-benzylamine Melting point: 164 - 146°C. 5 Prepared by saponification of N-ethyl-2-amino-3- bromo-5-cyano-N-cyclohexy1-benzylamine in sodium hydroxide solution analogously to Example 21.

Example 57 N-(2-Amino-5-carbamoy1-benzyl)-hexamethyleneamine 10 Melting point: 115 - 118°C.

Prepared by saponification of N-(2-amino-5-cyano-benzyl)-hexamethyleneamine in sodium hydroxide solution analogously to Example 21.

Example 58 15 N- ( 2- Amino- 3-bromo- 5-carbamoy 1-benzy 1) -hexamethy leneamine Melting point: 155 - 157°C.

Prepared by saponification of N-(2-amino-3-bromo-5-cyano-benzyl)-hexamethyleneamine in sodium hydroxide solution analogously to Example 21. 20 Exanple 59 2-Amino-5-carboxy-N,N-diethyl-benzylamine - 68 - 40146 Melting point of the hydrochloride: 104 - 198°C. Prepared by saponification of 2-amino-5-carbethoxy-N,N-diethy1-benzylamine in hydrochloric acid analogously to Example 20 Example 60 2-Amino-3-bromo-5-carboxy-N,N-diethy1-benzylamine Melting point of the hydrochloride: 233 - 234"C (decomp.).

Prepared by saponification of 2-amino-3-bromo-5-carbethoxy-N,N-diethy1-benzylamine in hydrochloric acid analogously to Example 20.

Examp1e 61 2-Amino-N-tert.-buty1-5-carboxy-benzylamine Melting point of the hydrochloride: 220 - 230"C. Prepared by saponification of 2-acetamino-N-tert.-butyI-5-cnrbethoxy-benzyInmine in hydrochloric ncid analogously to Example 52.

Example 62 2-Amino— 3-bromo-N-tert.-butyl-5-carboxy-benzylamine Melting point of the hydrochloride: 270 - 280"C (decomp.). - b9 - 4 0 110 Prepared by saponification of 2-amino- 3-bromo-N-lerL.-buty l-ri-carbethoxy-benzy lamine in hydrochloric acid analogously to Kxample 20.

Example 63 2-AceLamino-5-carboxy-N-cyclohexy1-N-methy1-benzylamine Melting point of the hydrochloride: 228 - 232°C. Prepared from 2-amino-5-carboxy-N-eyelohexy1-N-methy1-benzylamine and acetyl chloride analogously to Exanple 22.

Example 64 2-Amin<>- 3-bromo- 5-carboxy-N-cyclohexy 1-N-methy l-benzylaminc Melting point of the hydrochloride: 230 - 240"C. Prepared by saponification of 2-amino-3-bromo-5-carbethoxy-N-cyclohexy1-N-methy1-benzylamine in hydrochloric acid analogously to Example 20.

Example 65 N-F.thy I -2-amlno- 5-carboxy-N-cyc lohexy 1-benzy lamine Melting point of the dihydrochloride: 175 - 181 c. Prepared by saponification of N-ethyl-2-amino-r>-carbcLhoxy-N-cyclohexyI-benzylamine in hydrochloric - 70 - 40146 ncid analogously to Example 20.

Example 66 N-Ethyl-2-amino-5-carboxy-3-chloro-N-cyclohexy1-benzylamine Melting point of the hydrochloride: 228 - 232*C. Prepared by saponification of N-ethyl-2-amino-5-carbethoxy-3-chloro-N-cyclohexy1-benzylamine in hydrochloric ncid anaIogously Lo Example 20.

Example 67 2-Acetamino-5-cyano-N ,N-dimethy1-benzylamine Melting point of the hydrochloride: 244 - 245"C (decomp.).

Prepared from 2-acetamino- 5-cyano-benzy 1 bromide and dimethylamine analogously to Example 25.

Example 68 2-Amino-5-cyano-N.N-dimethy1-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. 4 0116 2-Amlno-3-bromo- 5-cyano-N ,N-dlmethy 1-benzy lamine Melting point of the hydrochloride: 250 - 255°C (decomp.).

Prepared from 2-amino-5-cyano-N,N-dimethy1-5 benzy lamine and bromine analogously to Example 28.

Example 70 2-Acetamino-5-cyano-N tN-diethyl-benzylamine Melting point: 80 - 82°C.

Prepared from 2-acetamino-5-cyano-benzyl bromide 10 and diethylamine analogously to Example 25.

Example 71 2-Amino-5-cyano-NtN-diethyl-benzylamine Melting point of the hydrochloride: 241 - 244°C. Prepared by saponification of 2-acetamino-5-cyano-15 N,N-diethyl-benzylamine in hydrochloric acid analogously to Example 34.

Example 72 2-Amino-3-bromo-5-cyano-N,N-diethy 1-benzy lamine Melting point of the hydrochloride: 226 - 229°C. 20 Prepared from 2-amino-5-cyano-N,N-diethy1- benzylamine and bromine analogously to Example 28. - 72 - 40146 Example 73 2-Acetamlno-5-cyano-N,N-dlpropy1-benzylamine Melting point: 80 - 82°C.

Prepared from acetamino-5-cyano-benzyl bromide and dlpropylamine annlogously to Example 25.

Example 74 2-Amino-5-cyano-N,N-dipropy1-benzylamine Melting point of the hydrochloride: 215 - 129"C. Prepared by saponification of 2-acetamino-5-cyano-N,N-dipropy1-benzylamine in hydrochloric acid analogously to Example 34.

Example 75 2-Acetnmino-N-tert.-butyl-5-cyano-benzylamine Melting point of the hydrochloride: 260 - 265"C. Prepared from 2-acetamino-5-cyano-benzyI 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 - 73 - <t 0 I I u analogously Lo Exartple 14.

Example 77 2-Amino-3-bromo-N-tert.-butyl-5-cyano-benzylamine Melting point: 78 - 80°C. r, Prepared from 2-nmino-N-tert.-butyl-5-cyano- benzy lamine and bromine analogously to Example 28. Example 78 2-Acetamino-5-cyano-N-cyclohexy1-N-methy1-benzylamine Melting point: 116-118°C. 10 Prepared from 2-acetamino-5-cyano-benzy1 bromide and N-methyl-cyclohexylamine analogously to Exanple 25. Example 79 2-Amino-5-cyano-N-eyelohexy1-N-methy1-benzylamine Melting point of the hydrochloride: 207 - 211"C. I r> Prepared by saponification of 2-acetnmino-5- cyano-N-cyclohexyl -N-methy1-benzylamine in hydrochloric ncid nnnlogously to Example 34.

Examp1e HO 2-Acetnmino-3-bromo-5-cyano-N-cyclohexy1-N-methy1-20 benzylamine - 74 - 40146 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. 5 Example 81 2-Acetamino-N-ethyl-5-cyano-N-cyclohexy1-benzylamine Melting point: 85 - 88°C.

Prepared from 2-acetamino-5-cyano-benzy1 bromide 10 and N-ethyl-eyelohexy lamine analogously to Ex.nmplc 25.

Example 82 2-Amino-N-ethy1-5-cyano-N-cyclohexy1-benzyInmine Melting point of the dihydrochloride: 201 - 206"C.. Prepared by saponification of 2-acetamino-N-I r» ethyl-5-cyano-N-cyclohexyl-benzylamine in hydrochloric acid analogously to Exanple 34.

Example 83 N-Ethy1-2-amino-3-bromo-5-cyano-N-cyclohexy 1-benzylamine Melting point of the hydrochloride: 194 - 197"C. 20 Prepared from N-ethyl-2-amino-5-eynno-N-cyclohexyl- benzyInmine nnd bromine analogously to Example 2X. - 75 - 40 110 Example 84 — 2-Acetamino-N-ethyl-N-benzyl-5-cyano-benzylamine Melting point: 112 - U3°C.

Prepared from 2-ncetamino-5-cyano-benzyI bromide 5 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-ethyI-M> N-benzyl-5-cyano-benzylamine in hydrochloric acid analogously to Example 34.

Example 86 N-Ethy1-2-amino-N-benzyl-3-bromo-5-cyano-benzylamine Melting point: 89 - 90°C. lr> Prepared from N-ethyl-2-amino-N-benzyl-5-cyano- benzy lamine and bromine analogously to Example 28.

Kx.-»nplo H7 2-Acetamino-N-bcnzy 1 - 5-cyano-N-propy 1-benzy lamine Melting point: 109 - 111°C. 20 Prepared from 2-acetamino-5-cyano-benzy1 bromide and N-propyl-benzylamine analogously to Example 25. - 76 - 40146 Example HH 2-Ainl ih>-N-Ih'h/.v l-5-cy:»no-n-|>ro|>y I -ben/.y Inmine Melting point: 61 - 64°C.

Prepared by saponification of 2-acetamino-N-5 benzyl-5-cyano-N-propyl-benzy lamine in hydrochloric acid analogously to Example 34.

Example 89 2-Amino-N-benzy1-3-bromo-5-cyano-N-propyl-benzylamine Melting point: 96 - 98"C. 10 Prepared from 2-amino-N-benzyl-5-cyano-N-propyl- benzyLimine and bromine analogously to Exanple 28. Example 90 2-Acetamino-N-benzyl-N-butyl-5-cyano-benzylamine Melting point: 65 - 66°C. 15 Prepared from 2-acetamino-5-cyano-benzy1 bromide and N-buty1-benzylamine analogously to Example 25. Example 91 2-Amino-N-benzy1-3-bromo-N-buty1-5-cyano-benzylamine Melting point: 71 - 73°C. 20 Prepared from 2-amino-N-benzyl-N-butyl-5-cyano- benzy lamine and bromine analogously to Example 28. - 77 - 4 0 11 U Example 92 N-(2-Acetamino-5-cyano-benzyl)-hexamethyleneamine Melting point: 108 - 110°C.

Prepared from 2-acetamino-5-cyano-benzy1 bromide 5 and hexamethyleneamine analogously to Example 25.

Example 93 N-(2-Amino-5-cyano-benzy1)-hexamethyleneamine Melting point of the hydrochloride: 228 - 232°C. Prepared by saponification of N-(2-acetamino-5-10 cyano-benzyl)-hexamethyleneamine in hydrochloric acid annlogously to Example 14.

Example 94 N-(2-Amino-3-bromo-5-cyano-benzy1)-hexamethyleneamine Melting point of the hydrochloride: 172 - 176"C. 15 Prepared from N-(2-amino-5-cyano-benzyl)-hexa- methyleneamine and bromine analogously to Example 28. Example 95 2-Acetnmino-3-bromo-N,N-5-trimethy1-benzylamine Melting point: 89 - 91°C. 20 Prepared from 2-amino-3-bromo-N,N,5-trimethyl- benzylamine and acetic anhydride analogously to Example 23. - 78 - 40146 Example 96 2-Amino- 3-bromo- N, N, 5-1 rlmethy 1-benzy lamine Melting point of the hydrochloride: 216 - 217°C. Prepared from 2-amino-3-bromo-5-methy1-benzy1 5 alcohol, thionyl chloride and dimethylamine analogously to Example 1.

Example 97 2-Acetamino-N-ethyl-3-bromo-N,5-dimethy1-benzylamine Melting point: 81 - 83°C. 10 Prepared from N-ethyl-2-amino-3-bromo-N,5-dimethyl- benzylamine and acetic anhydride analogously to Example 23.

Example 98 2-Amino-N-ethyl-3-bromo-Nt5-dimethy.l-benzy lamine lr> Melting point of hydrochloride: 199 - 200 'C.

Prepared from 2-amino-3-bromo-5-methy1-benzy1 alcohol, thionyl chloride and N-methy1-ethylamine analogously to Example 1.

Example 99 20 2-Acetamino-N,N-diethy1-5-methy1-benzylamine - 79 - 0116 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-diethy1-5-methy1-benzylamine Melting point of the dihydrochloride: 193 - 195"C. Prepared by saponification of 2-acetamino-N,N-dicthy l-r>-methy 1-benzy lamine in hydrochloric .ncid annlogously to Example 34.

Example 101 2-Amino-3-bromo-N^-diethyl-5-methy1-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 Kxnmple 1.

Example 102 2-Acct.imino-N-cyclohexy1-N,5-dlmcthy1-benzyInmine Melting point of the hydrochloride: 222 - 223"C. Prepared from 2-acetamino-5-methyl-benzyl bromide and N-methyl-cyclohexyInmine analogously to Example 6. - 80 - 40146 Example 103 2-Amlno-N-cyc lohexy I -N. r>-dime thy l-ben/yInmlno Melting point of the dihydrochloride: 203 - 205"C. Prepared by saponification of 2-acetamino-N-cyclohexyl-N,5-dimethy1-benzylamine in hydrochloric acid analogously to Example 34.

Example 104 2-Amino-3-bromo-N-cyclohexyl-Nt5-dimethy1-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 analogously to Example 1.

Example 105 2-Acetamino-3-bromo-N,5-dimeth/l-N-(cls-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 analogously to Example 24.

Example 106 - 81 - 40146 2-Amlno-3-bromo-N,5-dlmethyl-N-(cis-3-hydroxy-cyclohexy1)-benzylamine Melting point of the hydrochloride: 198°C.

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

Example 107 2-Acetanino-N-ethy1-N-cyclohexyl-5-methy1-benzylamine Melting point of the hydrochloride: 224 - 225"C. 10 Prepared from 2-acetamino-5-methyl-benzyl bromide and N-ethyl-cyclohexylamine analogously to Example 6.

Example 108 2-Amino-N-ethyl-3-bromo-N-cyclohexyl-5-methy1-benzyIamine Melting point of the hydrochloride: 186"c. 15 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)-20 benzylamine - 82 - 40146 Melting point of the hydrochloride: 212"C. Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and N-methy1-trans-4-hydroxy-cyclohexylamine analogously Example 1.

Example 110 2-Acetamino-N-benzy 1-3-bromo-N, 5-dimethy 1-benzy lamine Melting point of the hydrochloride: 210 - 212°C. Prepared from 2-amino-N-benzy1-3-bromo-N,5-dimethy1-benzylamine and acetic anhydride analogously to Example 23.

Example 111 2-Amino-N-benzy 1-3-bromo-N, 5-dimethy 1-benzy lamine Melting point of the hydrochloride: 220 - 222"C. Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and N-methy1-benzylamine analogously to Example 1.

Examp1e 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 ar.ilogously to Example - 83 - 4 0 116 Example 11.3 N- ( 2-Ainlno-3-bromo-5-methy 1-benzy 1)-pyrrolidine Melting point of the hydrochloride: 179 - I81"C. Prepared from 2-nmino-3-bromo-5-methyI-benzyI alcohol, thionyl chloride nnd pyrrolidine analogously to Example I.

Exnmp1c 114 N-(2-Acctnmlno-3-bromo-5-methy1-benzyl)-piperidlne Melting point of the hydrochloride: 252 - 253°C. Prepnred from N-(2-amino-3-bromo-5-methyl-benzy1)-piperidine and acetic anhydride analogously to Example 23 Exnmp I c I I 5 N-( 2-A»ni no- 3-bromo-5-methy 1-benzy I)-piperidine Melting point of the hydrochloride: 238 - 239"C. Prepared from 2-nmino-3-bromo-5-methyl-benzyI alcohol, thionyl chloride and piperidine analogously to Ex.nmplc 1.

Example life N-(2-Ami no-3-bromo-5-mcthy1-benzyl)-morpholine Melting point of the hydrochloride: 2A3 - 2/'4"C. - 84 - 40146 Prepared from 2-amino-3-bromo-5-methyl-benzyl alcohol, thionyl chloride and morpholine analogously to Example 1.

Example 117 N-(2-Acetomino-5-methy1-benzyl)-hexomethyleneamine Melting point of the hydrochloride: 164 - 165"C. Prepared from 2-ncetamino-5-methyl-benzyl bromide and hexamethyleneamine analogously to Example 6.

Example 118 N-(2-Amino-5-methy1-benzy1)-hexamethyleneamine Melting point of the dlhydrochloride: 205 - 207"C. Prepared by saponification of N-(2-acetamino-5-methy1-benzy1)-hexamethyleneamine in hydrochloric acid analogously to Example 34.

Example 119 N-(2-Amino-3-bromo-5-methy1-benzy1)-hexamethyleneamine Melting point of the hydrochloride: 193 - 194"C. Prepared from 2-amino-3-bromo-5-methy1-benzy1 alcohol, thionyl chloride and hexamethyleneamine analogously to Example I. 4 0116 Example 120 2-Aroino-3-bromo-N.N-dlmethyl-5-methoxy»benzvlamine Prepared from 2-amino-N,N-dimethyl-5-methoxy-benzylamine and bromine analogously to Example 9.

Proof of structure by IR-, UV- and NMR-spectra. IR-spectrum (methylene chloride): 3250 cm nh2 3410 cm 1 nh2 2780 cm ' n(ch 2H30 cm ' °CH3 1 5<>0 cm 1 c=c 1600 cm c=c Exnmp1e 121 2-Amino-N,N-dimethy1-5-methoxy-benzylamine I r, Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and dimethylamine, analogously to Example 1. Proof of structure by IR-, UV- and NMR-spectra. IR-spectrum (methylene chloride): 12H0 cm" ' Nil., 20 3420 cm" ' NH2 - 86 - 40146 2780 cm"1 N(CH3)2 2830 cm"1 OCH3 1600 cm * C=C Example 122 *> 2- Amlno-N tN-diethy 1-5-methoxy-benzy lamine Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and diethylamine analogpusly to Exanple 1. Proof of structure by IR-, UV- and NMR-spectra.

IR-spcclrum (methylene chloride): 3260 cin 1 nh2 3410 cm 1 nh2 2830 cm 1 och3 2800 cm 1 N-ethyl 1510 cm i c=c 1600 cm 1 c=c Example 123 2-Amino-J-bromo-N,N-diethy1-5-methoxy-benzylamine Prepared from 2-amino-N,N-diethy1-5-methoxy- ♦ benzy Ininine and bromine analogously to Example 9. 2° Proof of structure by IR-, UV- and NMR-spectra.

IR-spectrum (methylene chloride): - 87 - 4 0 116 10 lr> «# 2(> 3250 cm nh2 3410 cm" 1 nh2 2830 cm" 1 «»3 2800 cm N-ethy1 1480 cm" oc 1 590 cm c=c Examp1c 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. Proof of structure by IR-, UV- nnd NMR-spectra. IR-spectrum (methylene chloride): 1280 cm"' NH2 $420 cm"1 NH2 2830 cin"1 0CH3 2810 cm ' N-alkyl 1480 cm"1 C=C 1590 cm"' C=C Examp1e 125 2-Amino-3-bromo-N-cyclohexyl-5-methoxy-N-methy1-benzylamine - 88 - 40146 Prepared from 2-araino-N-cyclohexy1-5-methoxy-N-methy1-benzylamine and bromine analogously to Example 9. Proof of structure by IR- and UV-spectra.

IR-spectrum (methylene chloride): 3240 cm nh2 3410 cm nh2 2860 cm aliphatic hydrocarbon 2940 cm aliphatic hydrocarbon 2830 cm" och3 2800 cm N-alkyl 1480 cm c=c 1590 cm" c=c Examp1e 26 N-Ethy1-2-amino-3-bromo-N-cyclohexy1-5-methoxy-benzylamine Prepared from N-ethy1-2-amino-N-cyclohexy1-5-methoxy-benzylamine and bromine analogously to Example 9. Proof of structure by IR-, UV- and NMR-spectra.

IR-spectrum (methylene chloride): 3240 cm"1 NH2 3410 cm ' NH2 2860 cm ' aliphatic hydrocarbon - 89 - 40146 2940 cm 1 aliphatic hydrocarbon. 2830 cm"1 0CH3 2800 cm 1 N-ethy1 (shoulder) 1480 cm"1 C=C r» 1590 cm 1 C=C Example 127 N- ( 2-Amino- 5-methoxy-benzy 1)-morpholine Prepared from 2-amino-5-methoxy-benzyl alcohol, thionyl chloride and morpholine analogously to Example 1. 10 Proof of structure by IR- and UV-spectra.

IR-spcclrum (methylene chloride): 32HO cm nh2 3410 cm nh2 2830 cm*1 och3 2800 cm"1 N-alky1 1500 cm ' c=c 1600 cm 1 c=c Example 128 2-Amino-N-cyclohexy1-5-methoxy-N-methy1-benzyInmine 20 Prepared from 2-amino-5-methoxy-benzy1 alcohol, thionyl chloride and N-methyl-cyclohexylamine analogously - 90 - 40146 to Example 1.

Proof of structure by IR- and UV-spectra.

IR-spectrum (methylene chloride): 3240 cm"1 NH2 5 3400 cm"1 NH2 2780 cm 1 N-methy1 2830 cm"1 0CH3 2850 cm 1 aliphatic hydrocarbon 2930 cm 1 aliphatic hydrocarbon lo 1500 cm"1 C-C 1510 cm"1 OC Example 129 N-Ethy1-2-amino-N-cyclohexyl-5-methoxy-benzylamine Prepared from 2-amino-5-methoxy-benzy1 alcohol, 15 thionyl chloride and N-ethyl-cyclohexylamine analogously to Ex.imple 1.

Proof of structure by IR- and UV-spectrn. IR-spectrum (methylene chloride): _ 1 3250 cm nh2 1 3400 cm nh2 1 2830 cm 0ch - 91 - 40146 2800 cm ' N-ethyl (shoulder) 2850 cm 1 aliphatic hydrocarbon 2930 cm 1 aliphatic hydrocarbon 1500 cm 1 C-C 5 1600 cm 1 OC ExampIe 130 N-(2-Amino-3-bromo-5-methoxy-benzyI)-piperidine Prepared from N-(2-amino-5-methoxy-benzy1)-pipcridinc nnd bromine analogously to Example '). I(l Proof of structure by IR-, UV- and NMR-spectra.

IR-spcclrum (methylene chloride): nm cm" nh2 3400 cm nh2 2830 tin" 0ch} 2790 cm" N-nlky1 1480 cin c=c 1590 cin" c=c Examp1e 131 N-(2-Amino-5-methoxy-benzy1)-piperidine Prepared from 2-amino-5-methoxy-benzy1 alcohol, - 92 - 40146 thionyl chloride and piperidine by IR- and UV-spectra. IR-spectrum (methylene chloride): 3260 cm"1 NH2 3610 cm"1 NH2 2830 cm"1 0CH3 2800 cm 1 N-alkyl 1510 cm"1 C=C 1600 cm'1 OC Example 132 2-Amino-5-bromo-N-cyclohexy1-3-methoxy-N-methy1-benzylamine Melting point of the hydrochloride: 198 - 201°C. Prepared from 2-amino-N-cyclohexyl-3-methoxy-N-inethyI-benzylamine and bromine annlogously to Example 9. Example 133 1 r> U- Amino-3-bromo-N-cyc lohexy 1-5-methoxy-N-methy 1- benzyInmine Melting point of the hydrochloride: 177 - 180"C. Prepnred from 4-nmino-N-cyclohexyl-5-methoxy-N-incthyI-benzylamine nnd bromine nnnlogously to Example 9. 20 Example 1 14 N- ( 2-Amino- r»- f luoro-benzy 1) -hexamethy leneamine 5 10 - 9i - B-p- o.or ,6 * l00"c Prepared from 2-nmino-5-fluoro-N-hexnmothyIcnc-nmlno-bcnzamide and lithium aluminium hydride analogously to Example 35.

Example 135 N-(2-Amino-3-bromo-5-fluoro-benzy1)-hexamethyleneamine 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-benzy1)-morpholine Melting point of the hydrochloride: 230 - 232"C. Prepared from N-(2-amino-5-fluoro-benzy1)-morpholine nnd bromine analogously to Example 9.

Example 137 2-Amino-3-bromo-NtN-diethyl-5-fluoro-benzylamine Melting point of the hydrochloride: 182 - 184HC. Prepared from 2-amino-3-bromo-5-fluoro-benzy1 alcohol, thionyl chloride and diethylamine analogously to Example I. - 94 _ 40146 Example 118 N-Ethy1-2-amino-3-bromo-N-eyelohexy1-5-fluoro-benzy1amine Melting point of the hydrochloride: 176 - 178°C. Prepared from 2-amino-3-bromo-5-fluoro-benzy1 alcohol, thionyl chloride and N-ethyl-cyclohexylamine analogously to Example 1.

Example 139 N-Ethy1-2-amino-3-bromo-5-fluoro-benzylamine Melting point of the hydrochloride: 210 - 212°C. Prepared from 2-amino-3-bromo-5-fluoro-benzy1 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-ar.ino- 3-bromo -5-f luoro-benzy 1 alcohol, thionyl chloride and dimethylamine analogously to Example 1.

Example 141 2-Amino-3-bromo-N-cyclohexy1-5-fluoro-benzylamine - 95 - 146 Melting point of the hydrochlorides 250 - 252°C (decomp.).

Prepared from 2-amino-3-bromo-5-fluoro-benzy1 alcohol, thionyl chloride and eyelohexylamine analogously to Example 1.

ExampIe 142 2-Amino- {-bromo-5-fluoro-N-methy1-benzylamine Melting point of the hydrochloride: 215 - 2I7"C (decomp.).

Prepared from 2-amino-3-bromo-5-fluoro-benzy1 alcohol, thionyl chloride and methylamine analogously to Example 1.

Examp1e 143 2-AceLy1 amino-5-bromo-N-eyelohexy1-N-methy1->-(N-methy1-cyclohexy1-aminomethy1)-benzylamine Melting point: 194 - 199"C.

Prepared from 2-acetylamino-5-bromo-4-bromomethy1-benzyl bromide and N-methy1-cyclohexylamine annlogously to Example 1.

Example 144 - 96 - 40146 2-Acetylamino-5-bromo-N-(trans-4-hydroxy-cyclohexy1)-N-methy1-3-CN-me thyl-(trans-4-hydroxy-cyclohexy1amino)-me thy11-benzy1amine Melting point: 208 - 209°C. 5 Prepared from 2-acetylamino-5-bromo-3-bromomethy1- benzyl bromide and trans 4-raethylamino-cyclohexnno1 analogously to Example 3.

Example 145 2-Amino-N,N-diethy1-3-diethylaminomethy1-benzyInmine Melting point of the dihydrochloride: 199 - 201°C (decomp.).

Prepared by saponification of 2-acetylamino-N,N-diethyI-3-diethylaminomethyl-benzylamine in 2 N hydrochloric acid analogously to Example 14.

Example 146 2-Amino-5-bromo-N-(trans-4-hydroxy-eyelohexyl)-N-methy1 -3-fN-methy1-(trans-4-hydroxy-eyelohexylamino)-me thy1 "| -benzylamine Melting point: 179 - 180°C. 20 Prepared by saponification of 2-acetylamino-5- bromo-N-(trans-4-hydroxy-cyclohexyl)-N-methy1-3-[N- - 97 - 10 lr> 4 014 6 -methy J -(t rans-4-hydroxy-eyelohexylamino)-methy11-benzyInmine in 2 N hydrochloric acid analogously to Example 14.

Examp1e 147 r> 2-Acety lamino-N »N ,3-trimethyl-benzy lamine Melting point of the hydrochloride: 162 - 164"C. Prepared from 2-acetylamino-3-methyl-benzyl bromide and dimethylamine analogously to Example 2.

Examp1e 148 10 2-Acetylamino-N-ethy1-N,3-dimethyl-benzylamine Melting point of the hydrochloride: 168 170"C Prepared from 2-acetylamino-3-methyl-benzyl bromide and N-methylethylamine analogously to Example 2.

Example 149 1 5 2-Acety lamino-N ,N-dipropyl-3-methyl-benzylamine Melting point of the hydrochloride: 156 - 159°C. Prepared from 2-acetylamino-3-methyl-benzyl bromide nnd dipropylamine analogously to Example 2.

Example 150 20 2-Acetylamino-5-bromo-N,N,3-trimethy1-benzylamine - 98 - 40146 Melting point: 114 - 116"C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and dimethylamine analogously to Example 2. Exnmp le 1 *>1 2-Acety lamino-N-ethyl-5-bromo-N, 3-d imethy 1-benzy lamine Melting point: 81 - 83"C.

Prepared from 2-acetylomino-5-bromo-3-methyl-benzyl bromide and N-raethyl-ethylamine analogously to Example 2.

Example 152 2-Acely Inmino- 5-bromo-N,N-diethy I - 3-methy 1 -ben/.y I ami ne Melting point of the hydrochloride: 192.5 - 194 "C. Prepared frcm 2-acetylamino-5-bromo-3-methyl-benzyl bromide and diethylamine analogously to Example 2. Example 153 N-(2-Acetylamino-5-bromo-3-methy1-benzy1)-pyrrolidine romo-3-methy1-benzy1) - 99 - 40 1 JG Melting point: 119 - 124°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and piperidine analogously to Example 2.

Example 155 5 N-(2-Acetylamino-5-bromo-3-methy1-benzy1)-hexamethyleneamine Melting point: 129 - 132°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and hexamethyleneamine analogously to Example 2.

I<) Example I r>fe N- ( 2- Ace ty lamino- 5-bromo- 3-methy 1-benzy 1) -tnorpho line Melting point: 105 - 110nC.

Prepared from 2-acety lamino-* 5-bromo-3-methy 1-benzy 1 bromide and morpholine annlogously to Example 2.

I r» Example 157 2-Acetylamino-5-bromo-N-cyclohexy1-N,3-dimethy1-benzylamine Melting point: 102 - 104°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and N-methyl-cyclohexylamine analogously 20 to Example 2. - 100 - 4 0146 Example 158 2-Acetylamino-5-bromo-N>3-dimethyl-N-(cis-3-hydroxy-cyclohexyl)-benzylamine Melting point: 144 - 146°C.

Prepared from 2-acetylamino-5-bromo-3-methy1-benzyl bromide and cis-3-methylamino-cyclohexanol analogously to Example 2.

Examp1e 159 2-Acetylamino-5-bromo-N,3-dimethyl-N-(trans-4-hydroxy-cyclohexy1)-benzylamine Melting point: 136.5 - 138"C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and trnns-4-methylamino-cyclohexanol analogously to Example 2.

Example 160 2-Acetylamino-N-ethy1-5-bromo-N-cyclohexy1-3-methy1-benzylamine Melting point: 115 - 119°C.

Prepared from 2-acetylamino-5-bromo-3-methyl-benzyl bromide and N-ethyl-cyclohexylamine analogously to Example 2. - 101 - 40146 Ex/imp I e 11> I 2-AcetyIamino-N-ethy1-5-bromo-N-(trans-4-hydroxy-cyc lohoxy I)- 1-meLhy I-benzylamino Melting point: 168 - 170"C. 5 Prepared from 2-acetylamino-5-bromo-3-methy l- ben/.yl bromide and trnns-4-ethy lamino-cyclohexanol analogously to Example 2.

Example 162 2-AceLyl.nnino-N-benzyl-5-bromo-N,3-dimethy1-benzylamine 10 Melting point: 97 - 99"C.

Prepared from 2-acetylamino-5-bromo-3-methy1-benzyl bromide and N-methyl-benzylamine analogously to Example 2.

Example 16 3 I r> N- ( 2-Acety lamino- 5-bromo- 3-methy I -benzy 1) -N' -methy l- piperazine Melting point of the dihydrochloride: 256 -257"C (decomp.)- Prepared from 2-acetylamino-5-bromo-3-methy 1-2l> benzyl bromide and N-methyl-piperazine analogously to Example 2. - 102 - 40146 i Example IbA 2-Amino-NtN, 3- tritnethy 1-benzy lamine Melting point of the dihydrochloride: 188 - 190°C. Prepared by saponification of 2-acetylamino-N,N,3-5 trimethy1-benzylamine in 2 N hydrochloric acid analogously to Example 13.

Example 165 N-Ethy 1-2-amino-N, 3-dimethyl-benzylamine Melting point of the dihydrochloride: 196 -10 198"C (decomp.).

Prepared by saponification of 2-acetylamino-N-ethy1-N,3-dimethyl-benzylamine in 2 N hydrochloric acid annlogously to Example 13.

Example 166 1 "> 2-Amino-N ,N-dipropy 1- 3-methy 1-benzy lamine Melting point of the dihydrochloride: 168 - 173'C (decomp.).

Prepared by saponification of 2-acetylamino-N ,N-dipropyl-3-methyl-benzylamine in 2 N hydrochloric acid 20 analogously to Example 13. - 103 - 4 0116 Example Ib7 2-Ami no-l>-hromo-N,N ,3-Lrlmethyl-benzylamine Melting point of the hydrochloride: 218 - 221"C (decomp.).

Prepared by saponification of 2-acetylamino-r>-bromo-N,N,3-trimethy1-benzylamine in 2 N hydrochloric acid analogously to Example 13.

Example 168 N-EthyI-2-amino-5-bromo-N,3-dimethyl-benzylamine Melting point of the hydrochloride: 191 - 193'C (decomp.).

Prepared by saponification of 2-acetylamino-N-cthy I-r)-bromo-N, 3-dimethyl-benzylamine in 2 N hydrochloric acid analogously to Example 31.

Examp1e 169 2-Amino-5-bromo-N,N-diethy1-3-methyl-benzylamine Melting point of the hydrochloride: 177 - 179"C (decomp.).

Prepared from 2-araino-N,N-diethy1-3-methy1-benzylainine hydrochloride and bromine analogously to F.xamp I e 10.

- I OA - 40146 Example 170 N-(2-Amino-5-bromo-3-methy1-benzy1)-pyrrolidine Melting point of the dihydrochloride: 206 -210°C (decomp.)* 5 Prepared by saponification of N-(2-acetylamino-5- bromo-3-methy1-benzyl)-pyrrolidine in 2 N hydrochloric acid analogously to Example 13.

Example 171 N-(2-Amino-5-bromo-3-methy1-benzy1)-piperidine 10 Melting point of the dihydrochloride: 176 - 179"C (decomp.).

Prepared by saponification of N-(2-acetylamino-5-bromo-3-methy1-benzy1)-piperidine in 2 N hydrochloric acid analogously to Example 13. 1 r> Example 172 N-(2-Amino-5-bromo-3-methy1-benzy1)-hexamethyleneamine Melting point of the dihydrochloride: 159 -164"C (decomp.).

Prepared by saponification of N-(2-acetylnmino-5-20 bromo-3-methyl-benzyl)-hexamethyleneamine in 2 N - 105 - 4 0116 hydrochloric acid analogously to Example 13.

Example 173 N-(2-Amino-5-bromo-3-methy1-benzy1)-morpholine Melting point of the dihydrochloride: 159 - 163"C (decomp.)« Prepared by saponification of N-(2-acetylamino-5-bromo-3-methyl-benzyl)-morpholine in 2 N hydrochloric acid analogously to Example 13.

Example 174 2-Amino-5-bromo-N-(trans-4-hydroxy-cyclohexyl)-3-methy1-benzylamine Melting point of the hydrochloride: 225 -226"C (decomp.).

Prepared by saponification of 2-acetylamino-5-bromo-N-(trans-4-hydroxy-cyclohexyl) -3-methy 1-benzy lamine in 2 N hydrochloric acid analogously to Example 13. ExampIc 175 2-Amino-5-bromo-N-cyclohexy 1-N,3-dimethyl-benzylamine Melting point of the hydrochloride: 206.5 -207.5"C (decomp.) - 106 - 40146 Prepared by saponification of 2-acetylamino-5-bromo-N-cyclohexy1-N,3-dimethyl-benzylamine in 2 N hydrochloric acid analogously to Example 13.

Example 176 2-Amino-5-bromo-N,3-dimethyl-N-(cis-3-hydroxy-cyclohexyl)-benzyInmine Melting point: 118 - 119°C.

Prepared by saponification of 2-acetylamino-5-bromo-N,1-dimethyl-N-(cis-3-hydroxy-cyclohexyl)-benzyInmine in 2 N hydrochloric ncid analogously to Excimple 11.

Examp1c 177 2-Amino-r>-bromo-N, l-dimethyl-N-( t mns-4-hydroxy-cyc lohexy I )-benzyInmine Melting point: 122 - 123.5°C.

Prepared by saponification of 2-acetylamino-5-bromo-N,3-dimethy1-N-(trans-4-hydroxy-cyclohexy1)-benzylamine in 2 N hydrochloric acid analogously to Example 13.

Example 178 N-Ethy1-2-amino-5-bromo-N-cyclohexyl-3-methy1-benzylamine - 107 - 40146 Melting point of the dihydrochloride: 183 -187"C (decomp.).

Prepared by saponification of 2-acetylatnino-N-ethyl-5-brotno-N-cyc lohexy 1-3-methy 1-benzy lamine in 2 N hydrochloric acid analogously to Example 13.

Example 179 N-Ethy1-2-amino-5-bromo-N-(trans-4-hydroxy-cyclohexy1)-3-methy1-benzylamine Melting point of the hydrochloride: 156 - 161"C (decomp.).

Prepared by saponification of 2-acetylamino-N-ethy1 -5-bromo-N-(trans-A-hydroxy-cyclohexyl)-3-methy1-benzyInmine in 2 N hydrochloric acid analogously to Example n.

Example 180 2-Amino-N-benzy1-5-bromo-N, 3-dimethyl-benzylamine Melting point of the hydrochloride: 214 - 216'C (decomp.).

Prepared by saponification of 2-acetylamino-N-benzyl-5-bromo-N,3-dimethyl-benzylamine in 2 N hydrochloric acid analogously to Example 13. - 108 - 40146 Example 181 2-Acetylamino-4-tert.-buty1-N-cyclohexy1-N-methyl-benzylamine Melting point of the hydrochloride: 231 - 234"C Prepared from 2-acetylamino-4-tert.-butyl-benzyl bromide nnd N-methyl-cyclohexylamine analogously to Example 4.

Example 182 2-Acety lamino- 5-bromo-4-tert. - buty 1-N, N-dimethy 1-benzy lamine Melting point: 111 - 113°C.

Prepared from 2-acety lamino- 5-bromo-4-tert.-butyl benzyl bromide and diraethylamine analogously to Example 4. Example 183 2-Acety lamino- 5-bromo-4-tert. -buty 1-N, N-diethy 1-benzy lamine Melting point: 88 - 91"C.

Prepared from 2-acety lamino-5-bromo-4-tert.-butyl-benzyl bromide and diethylamine analogously to Example 4. Example 184 2-Acetylnmino-5-bromo-4-tert.-buty1-N-(hydroxy-tert.-buty1)-benzylamine - 109 - 40146 Melting point: 125 - 127°C.

Prepared from 2-acetylamino-5-bromo-4-tert.-butyl-benzyl bromide nnd hydroxy-tert.-butylamine analogously to Example 4. r> Example 185 N-( 2-Acetyalmino-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 analogously to Example 4. 10 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 analogously to Example 4. 15 Example 187 N-(2-Acetylamino-5-bromo-4-tert.-butyl-benzyl)-morpholine Melting point: 136 - 139°C.

Prepared from 2-acetylanino-5-bromo-4-tert.-butyl-benzyl bromide and morpholine analogously to Example 4. 20 Example 188 - 110 - 40146 2-Acetylamino-5-bromo-4-tert.-buty1-N-(els-3-hydroxy-cyclohexyl)-N-methy1-benzylamine Melting point: 167 - 172"C.

Prepared from 2-acetylamino-5-bromo-4-tert.-buty1-5 benzyl bromide and cis-3-methylamino-cyclohexanol analogously to Example 4.

Example 189 2-Acetylamino-5-bromo-4-tert.-buty1-N-(trans-4-hydroxy-cyclohexyl )-N-methy 1-benzy lamine 10 Melting point: 174 - 176°C.

Prepared from 2-acetylamino-5-bromo-4-tert.-butyl-benzyl bromide and trans-4-methyl-amino-cyclohexanol analogously to Example 4.

-- Ill - 40 1 46 Example 190 2-Acetylamino-N-ethyl-5-bromo-4-tert.- buty1-N-cyclohexy1-benzylamine Melting point: 102 - 105°C. 5 Prepared from 2-acetylamino-5-bromo-4-tert.-butyl- benzyl bromide and N-ethyl-cyclohexylamine analogously to Example 4.

Example 191 N-(2-Acetylamino-5-bromo-4-tert.-buty1-benzy1)-N'-methy1-10 piperazine Melting point of the dihydrochloride: >250°C (decomp). Prepared from 2-acetylamlno-5-bromo-4-tert.-butyl-benzyl bromide and N-methylpiperazine analogously to Example 4. 1 *) Example 192 N-(2-Acctylamino-5-bromo-4-tert.-buty1-benzyl)-camphidinc Melting point: 133 - 138°C.

Prepared from 2-acetylamino-5-bromo-4-tert.-butyl-benzyl bromide and camphidine analogously to Example 4. -112- 40146 Example 193 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.-5 butyl-N ,N-diethyl-benzylamine in aqueous ethanolic hydrochloric acid analogously to Example 15.

Example 194 2-Amino-4-tert.-butyl-N-cyclohexyl-N-methyl-benzylamine Melting point of the dihydrochloride: 198 - 199UC. 10 Prepared by saponification of 2-acetylamino-4-tert.- butyl-N-cyclohexyl-N-methyl-benzylamine in 3 N hydrochloric acid analogously to Example 15.

Example 195 2-Amino-5-bromo-4-tert.-butyl-N,N-dimethyl-benzylamine 1 r> Melting point of the dihydrochloride: 213 to 218°C (decomp.).

Prepared by saponification of 2-acetylamino-5-bromo-4 tert.-butyl-N,N-dimethyl-benzylamine in 3 N hydrochloric acid analogously to Example 15. - 113 - 40146 Example 196 2-Amino-5-bromo-4-tert»-butyl-N ,N-diethyl-benzy lamine Melting point of the hydrochloride: 198 - 200°C (decomp). 5 Prepared by saponification of 2-acetylamino-5-bromo- 4-tert.-butyl-N,N-diethyl-benzylamine in 3 N hydrochloric acid analogously to Example 15.

Example 197 2-Amino- 5-bromo-4- tert .-butyl-N , N-dially 1-benzy lamine 10 Melting point of the hydrochloride: 176 - 178°C.

Prepared by saponification of 2-acetylamino-5-broino-4-terL.-butyl-N ,N-dlally1-benzylamine in 3 N hydrochloric acid analogously to Example 15.

Example 198 1 r> 2-Amino-5-bromo-4-ter^ .-buty 1-N-(hydroxy-tert.-butyl )- benzylamine Melting point: 123 - 125°C.

Prepared by saponification of 2-acetylamino-5-bromo-4-tert.-butyl-N-(hydroxy-tert.-butyl)-benzylamine in 3 N 20 hydrochloric acid analogously to Example 15.

- LL4 - 40146 Example 199 2-Amino-5-brorao-4-tert.-butyl-N-(I,3-dihydroxy-2-methyl-propy1-2)-benzylamine Melting point of the dihydrochloride: 200 - 205°C (decomp).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert.-butyl-N-(1,3-dlhydroxy-2-methyl-propy1-2)-benzylamine in 4 N hydrochloric acid analogously to Example 15.

Example 200 N-Ethyl-2-ami no-5-bromo-3-carboxy-N-cyc 1 ohexyl - benzylamine M.P. of the hydrochloride: 130 to 140°C Prepared from 2-amino-5-bromo-3-carboxy-benzyl bromide and N-ethylcyclohexylamine analogously to Example 25.

Example 201 N-(2-Amino-5-bromo-4-tert.-buty1-benzy1)-pyrrolid1ne Melting point of the hydrochloride: > 190°C. (decomp). Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert.-butyl-benzyl)-pyrrolidine in 3 N hydrochloric - 115 - 40146 acid analogously to Example 15.

Example 202 N-(2-Amino-5-bromo-4-tert.-buty1-benzyl)-piperidinc Melting point of the dihydrochloride: 188 - 195°C. 1 Prepared by saponification of N-(2-acetylamino-5- bromo-4-tert.-butyl-benzyl)-piperidine in 3 N hydrochloric acid analogously to Example 15.

Example 203 N-(2-Amino-5-bromo-4-tert.-butyl-benzyl)-morphollne 10 Melting point of the dihydrochloride: 194 - 198°C (decomp.).

Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert.-butyl-benzyl)-morpholine in 3 N hydrochloric acid analogously to Example 15. lr> Example 204 2-Amino-5-bromo-4-tert.-butyl-N-(trans-4-hydroxy-cyclo- hexyl)-benzylamine Melting point of the dihydrochloride: 212 - 218°C (decomp.). 20 Prepared by saponification of 2-acety lamino-5-broino- 4-tert.-buty1-N-(trans-4-hydroxy-cyclohexyl)-benzylamine in 4 N hydrochloric acid analogously to Example 15. - 116 - 40146 Example 205 2-Amino-5-bromo-4-tert.-butyl-N-(c is-3-hydroxy-cyclohexy1)-N-methy1-benzylamine Melting point of the dihydrochloride: 205 - 208°C r> (decomp.).

Prepared by saponification of 2-acetylamino-5-bromo-4-tert.-butyl-N-(cis-3-hydroxy-cylcohexyl)-N-methy1-benzylamine in 4 N hydrochloric acid analogously to Example 15. 10 Example 206 2-Amino-5-bromo-4-tert.-buty1-N-(t rans-4-hydroxy-cyclo- hexyl)-N-methyl-benzylamine Melting point of the hydrochloride: 208 - 210°C (decomp.). 15 Prepared by saponification of 2-acetylamino-5-bromo- 4-tert.-buty1-N-(trans-4-hydroxy-cyclohexyl)-N-methy1-benzylamine in 3 N hydrochloric acid analogously to Example 15.

Example 207 20 N-Ethy1-2-amino-5-bromo-4-tert.-butyl-N-cyclohexyl- benzylamine Melting point of the hydrochloride: 191 - 194°C (decomp.). - 117 - 40146 Prepared by saponification of 2-acetylamlno-N-cthyl-5-bromo-4-tert.-buty1-N-cyclohexyl-benzylamine In aqueous ethanolic hydrochloric acid analogously to Example IS.

Example 208 N-(2-Amino-5-bromo-4-tert.-buty1-benzy1)-N'-methy1- piperazine Melting point of the trihydrochloride: 170 - 180°C (decomp.).

Prepared by saponification of N-(2-acetylamino-5-bromo-4-tert.-butyl-benzyl)-N'-methyl-piperazine in 3 N hydrochloric acid analogously to Example 15.

Example 209 N-(2-Amino-5-bromo-4-tert.-butyl-benzyl)-camphidine Melting point of the dihydrochloride: 198 - 205°C (decomp.).

Prepared by saponification of N-(2-acelylamino-5-bromo-4-tert.-butyl-benzyl)-camphidine in 3 N hydrochloric acid analogously to Example 15. - 118 - 40146 Example 210 4-Amino-3-tert.-butyl-N.N-dlethy1-benzylamine Melting point of the dihydrochloride: 183 - 185°C (decomp.). ■> Prepared by saponification of 4-acetylamino-3-tert.- butyl-N,N-diethyl-benzylamine in 3 N hydrochloric acid analogously to Example 17.

Example 211 4-Amino-5-bromo-3-tert.-butyl-NtN-diethyl-benzylamine 10 Melting point of the dihydrochloride: 201 - 204°C (decomp.).

Prepared from 4-amino-3-tert.-butyl-N,N-diethyl-benzylamine dihydrochloride and bromine analogously to Example 10. 15 Example 212 4-Amino-5-bromo-3-tert.-buty1-N-cyclohexy1-N-methy1-benzylamine Melting point of the hydrochloride: 198 - 201"C (decomp). 20 Prepared from 4-amino-3-tert.-butyl-N-cyclohexyl-N- methyl-benzy lamine dihydrochloride and bromine analogously - 119 - 40146 to Example 10.

Example 213 5-Acetyl-2-acetylamino-N,N-diethy1-benzylamine Melting point: 102 - 103°C. r> Prepared from 5-acetyl-2-acetylamino-benzyl bromide and diethylamine analogously to Example 8.

Example 214 5-Acety1-2-acetylamino-N,N-dipropy1-benzylamine Melting point: 80 - 82°C. 10 Prepared from 5-ncetyl-2-acetylamino-benzyl bromide nnd dipropylamine annlogously to Example 8.

Examp1e 215 *)- AceLy 1- 2-acety lamino-N ,N-dlbuty 1-benzy lamine Melting point: 40 - 42"C. 1*> Prepared from 5-acetyl-2-acetylamino-benzyl bromide and dibutylamine analogously to Example 8.

Example 216 N-(5-Acety1-2-acetylamino-benzyl)-pyrrolidine Melting point: 88 - 90°C. 20 Prepared from 5-acetyl-2-acetylamino-benzyl bromide and pyrrolidine analogously to Example 8. - 120 - 4 014 6 Example 217 N-(5-Acety1-2-acetylamino-benzyl)-piperidine Melting point of the hydrochloride: 210 - 212"C. Prepared from 5-acety1-2-acetylamino-benzyl bromide and piperidine analogously to Example 8.

Example 218 N-(5-Acety1-2-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-Acety1-2-acetylamino-benzyl)-morpholine Melting point: 100 - 102°C.

Prepared from 5-acetyl-2-acetylamino-bcnzy1 bromide and morpholine analogously to Example 8.

Example 220 5-Acety1-2-acetylamino-N-cyclohexy1-N-methy1-benzylamine Melting point of the hydrochloride: 210 - 211°C. Prepared from 5-acetyl-2-acetylamino-benzyl bromide and N-methyl-eyelohexylamine analogously to Example 8. - 121 - 40146 Example 221 5-Acety 1-2-acetylamino-N-ethyl-N-cyclohexy1-benzylamine Melting point: 98 - 100°C.

Prepared from 5-acetyl-2-acetylamino-benzyl bromide r> and N-ethyl-cyclohexy lamine analogously to Example 8.

Example 222 5-Acetyl-2-acetylamino-N-cyclohexy1-N-isopropy1-benzylamine Melting point: 108 - 110°C.

Prepared from 5-acety1-2-acetylamino-benzyl bromide 10 and N-isopropyl-cyclohcxylamine analogously to Example 8.

Example 223 N-(5-Acety1-2-acetylamino-benzyl)-N' -methy1-piperazine Melting point of the dihydrochloride:>275°C (decomp.). Prepared from 5-acetyl-2-acetylamino-benzy1 bromide 1r> and N-mcthyl-piperazinc analogously to Example 8.

Example 224 5-Acetyl-2-amino-N,N-diethy1-benzylamine Melting point of the hydrochloride: 218 - 221°C. Prepared by saponification of 5-acetyl-2-acetylamino-20 N,N-diethy1-benzylamine in aqueous ethanolic sodium hydroxide solution analogously to Example 18. - 122 - 40146 Example 225 5-Acetyl-2-amino-NtN-dipropyl-benzylamine Melting point of the hydrochloride: 171 - 173WC. Prepared by saponification of 5-acetyl-2-acetylamino-r> N,N-dipropyl-benzylamine in aqueous ethanolic sodium hydroxide solution analogously to Example IK.

Example 22b 5-Acetyl-2-amino-N ,N-dibutyl-benzylamine Melting point of the hydrochloride: 110 - 120°C. 10 Prepared by saponification of 5-acetyl-2-acetylamino- N ,N-dibutyl-benzylamine in 4 N hydrochloric acid analogously to Example 16.

Example 227 N-(5-Acetyl-2-amino-ben2yl)-pyrrolidine lr> Melting point of the hydrochloride: 203 - 205°C.

Prepared by saponification of N-(5-acetyl-2-acetyl-amino-benzyl)-pyrrolidine in aqueous ethanolic sodium hydroxide solution analogously to Example 18. - 123 - 40146 Example 228 N-(5-Acetyl-2-amlno-benzyl)-piperidine MeltinR point of the hydrochloride: 220 - 222°C. Prepared by saponification of N-(5-Acety1-2-ncetyl-r> amino-benzyl )-piperidine in aqueous ethanolic sodium hydroxide solution analogously to Example 18.

Example 229 N-(5-Acety1-2-amino-benzyl)-hexamethyleneamine Melting point of the hydrochloride: 205 - 207°C 10 (decomp.).

Prepared by saponification of N-(5-acetyl-2-acetylamino -benzy1)-hexamethyleneamine in aqueous ethanolic sodium hydroxide solution analogously to Example 18.

Kxample 230 I r> N-(5-Acety 1-2-amino-benzyl)-morpholine Melting point of the hydrochloride: 218 - 220°C (decomp.).

Prepared by saponification of N-(5-acetyl-2-acctyl-amino-henzyl)-morpholine in aqueous ethanolic sodium 20 hydroxide solution analogously to Example 18. - 124 - 40146 Example 231 5-Acetyl-N-ethyl-2-amino-N-cyclohexyl-benzylamine Melting point: 100 - 102°C.

Prepared by saponification of 5-acetyl-2-acetylamino-r> N-ethyl-N-cyclohexy 1-benzy lamine in aqueous ethanolic sodium hydroxide solul.Ion analogously to Example 18.

Example 232 N- ( 5-Acetyl-2-amlno-bi;nzyl)-N' -methy 1-piperazine Melting point: 1$5 - 138°C. 10 Prepared by saponification of N-(5-acetyl-2-acetyl- amino-benzyl)-N'-methyl-piperazine in aqueous ethanolic sodium hydroxide solution analogously to Example 18.

Example 233 5-Acetyl-2-amino-3-bromo-NtN-diethy1-benzylamine 15 Melting point of the hydrochloride: 208 - 212°C.

Prepared from 5-acetyl-2-amino-N,N-diethyl-benzylamine hydrochloride and bromine analogously to Example 11. - 125 - Example 234 5-Acetyl-2-amlno-3-bromo-N,N-dipropy1-benzylamine Melting point of the hydrochloride: 136 - 140°C. Prepared from 5-acetyl-2-amino-N,N-dipropyl-benzylamine hydrochloride and bromine analogously to Example 11.

Example 235 5- Acetyl- 2-amino- 3-bromo-N ,N-dlbuty 1-benzy lamine M.p. of the hydrochloride: 112 to 115°C.

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

Example 236 N-(5-Acetyl-2-amino-3-bromo-benzyl)-pyrrolidine M.p. of the hydrochloride: 165 to 167°C.

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

Example 217 N-(5-Acetyl-2-amino-3-bromo-benzyl)-piperidine M.p.: 108 to 110°C.

Prepared from N-(5-acetyl-2-amino-benzyl)-piperidine hydrochloride and bromine analogously to Example 11. - 126 - 4 0116 Example 23H N-(5-Accty L-2-amlno-3 bromo-benzyl)-hexamethyleneamine M.p. of the hydr--chloride: 203 to 206°C.

Prepared from N- 5-acetyl-2-amino-benzyl)-hcxamethy1-eneamlne hydrochlorid and bromine analogously to Example 11.

Example 239 N-(5-AceLyL-2-amino-l bromo-benzyI)-morphoIi ne M.p. of the hydr chloride: 235 to 239T. (decomp.). Prepared from N- 5-acetyl-2-ninino-benzy l)-morphol i iu hydrochloride and brer ine analogously to Example 11. Example 240 5-Acety1-2-amino-3-br mo-N-cyclohexy1-N-methy i-benzylamine M.p. of the hydr chloride: 229 to 231UC.

Prepared from 5- cetyl-2-amino-N-cyclohexyl-N-mithyl-benzylamine dihydroch oride and bromine analogously to Example 11.

Example 241 5-Acct1 -N-ethy 1-2-am no-3-bi mo-N-cy c lohexy 1-benzy laini in-M p.: Ill to 113 C.

Prepared from 5- cetyl-N-ethyl-2-amino-N-cyclohexy1-benzyl.unine and bromi e analogously to Example 11. - 127 - 40146 Example 242 N-(5-Acetyl-2-amino-3-bromo-benzyl)-N'-methy1-piperazine M.p.: 99 to 104°C.

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

Example 243 i 2-Amino-3-bromo-N,N-dimethy1-5-(1-hydroxy-ethyl)-benzyl- amine M.p.: 69 to 72"C. 1" Prepared by reduction of 5-acetyl-2-anuno-3-brn"so- N,N-dimethyl-benzylamine with sodium borohydride analogously to Example 19.

Example 244 2-Amino-3-bromo-N,N-diethy1-5-(1-hydroxy-ethyl)- lr> henzy lamine M.p.: 62 to 65°C.

Prepared by reduction of 5-acetyl-2-amino-3-bromo-N, "i-diethyl-benzy lamine with sodium borohydride analogously *-o Example 19. 20 Example 245 2-Anirto-3-bromo-N ,N-dipropyl-5-(l-hydroxy-ethyl)-benzvlamine ^.p.: 52 to 54UC. - 128 - 40146 Example 242 N-(5-Acetyl-2-amino-3-bromo-benzyl)-N'-methyl-piperazine M.p.: 99 to 104"C.

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

Example 243 i 2-Amino-3-bromo-N,N-dimethyl-5-(l-hydroxy-ethyl)-benzyl- amine M.p.: 69 to 72°C. 10 Prepared by reduction of 5-acetyl-2-amino-3-bromo- N,N-dimethyl-benzylamine with sodium borohydride analogously to Example 19.

Example 244 2-Aniino-3-bromo-N ,N-dicthyl-5-(l-hydroxy-ethyl)- 1 r> benzylamine M.p.: 62 to 65°C.

Prepared by reduct ion of 5-acetyl-2-amino-3-bromo-N, N-diethyl-benzylamine with sodium borohydride analogously to Example 19. 20 Example 245 2-Amino-3-bromo-N,N-dipropyl-5-(l-hydroxy-ethyl)-benzylamine M.p.: 52 to 54°C. - 128 - 40148 Prepared by rciliu-L ion of 5-;ict'lyl-2-nmlnn-3»hrnnin-N,N-dIpropylbenzylamine with sodium borohydride analogously to Example 19.

Example 246 5 2-Amino-3-bromo-N,N-di butyl-5-(l-hydroxy-ethyl)-benzy1- arnine M.p.: 48 to 51°C.

Prepared by reduction of 5-acetyl-2-amino-3-bromo-N ,N-dibutyl-benzylamine with sodium borohydride 10 analogously to Example- 19.

Example 247 N-[2-Amino-3-bromo-5-(l-hydroxy-ethyl)-benzyl]-pyrrolidine M.p.: 98 to 102°C.

Prepared by reduction of N-(5-acetyl-2-amino-3-bromo-1 r> benzyl)-pyrrolidine with sodium borohydride analogously to Example 19.

Example 248 N-Ethyl-2-amino-3-bromo-N-cyclohexy1-5-(1-hvdroxy-ethyl)-benzylamine 20 M.p.: 117 to 121JC.

Prepared by reduction of 5-acetyl-N-ethyl-2-amino-3-- 129 - 40146 bromo-N-cyclohexy1-benzylamine with sodium borohydride analogously to Example 19.

Example 249 N-I2-Amino-3-bromo-5-(1-hydroxy-ethyl)-benzyl]-N*-methyl- 5 piperazine M.p.: 134 to 13buC.

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

O Example 250 2-Amino-N-isopropyl-3-trifluoromethy1-benzylamine M.p. of the hydrochloride: 188 to 189°C.

Prepared from 2-amino-3-trifluoromethyl-benzy1 chloride and isopropylamine analogously to Example 1. r» Example 251 2-Amino-N ,N-diethy1-3-trifluoromethy1-benzylamine M.p. of the hydrochloride: 194 to 196°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and diethylamine analogously to Example 1. - 130 - 40146 Example 252 N-(2-Amino-3-trlfluor<>methyl-benzyl)-hexamethyleneamine M.p. of the hydrochloride: 208 to 209°C.

Prepared from 2-nmino-3-trifluoromethyl-benzyl 5 chloride and hexamethyleneamine analogously to Example 1.

Example 253 N-Ethy1-2-amlno-N-cyclohexy1-3-trifluoromethyl-benzylamine M.p. of the hydrochloride: 189 to 191°C.

Prepared from 2-amino-3-trifluoromethyl-benzyl 10 chloride and N-ethyl-cyclohexylamine analogously to Example 1.

Example 254 2-Amino-N-methyl-N-(morpholino-carbonyl-methyl)-3-t rlfluoromethyl-benzylamine lr> M.p. of the hydrochloride: 200 to 203°C (decomp.).

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and sarcosine-morpholide analogously to Example 1. Example 255 2-Amino- 5-bromo-N-isopropyl-3-trif luoromethyl-benzy lamine 20 M.p. of the hydrochloride: 206 to 208°C.

Prepared from 2-amino-N-isopropyl-3-trifluoromethyl- - 131 - 40146 benzylamine and bromine analogously to Example 10.

Example 256 2-Amino-5-bromo-N,N-diethy1-3-1ri fluoromethyl-benzylamine M.p. of the hydrochloride: 198 to 200°C.

Prepared from 2-amino-N,N-diethyl-3-trifluoromethyl-benzyInmine and bromine analogously to Example 10.

Example 257 N-(2-Amino-5-bromo-3-trifluoromethyl-benzyl)-hexamethyleneamine M.p. of the hydrochloride: 223 to 225°C.

Prepared from N-(2-amino-3-trifluoromethyl-bcnzyl)-hexamethyleneamine and bromine analogously to Kxample 10. Kxamp1 e 2 5K N-Ethy 1 - 2-amino- 5-broino-N-cyc lohexy 1-3- trif luoromethy 1- benzylamine M.p. of the hydrochloride: 204 to 207°C.

Prepared from N-eLhyl-2-amino-N-cyclohexyl-3-trifluoromethyl-benzy Limine and bromine analogously to KxampIf 10. - 132 - 40146 Example 259 2-Amino-5-bromo-N-methy1-N-(morpholino-carbonyl-methyl)- 3-trlf luoromethy l-ben/.y lamine M.p. of the hydrochloride: 211 to 215°C (decomp.). 5 Prepared from 2-amino-N-methyl-N-(morpholino-carbonyl- methyl)-3-trifluoromeLhyl-benzylamine and bromine analogously to Example 10.

Example 260 2-Amino-5-chloro-N-isopropy1-3-trifluoromethyl-benzylamine 10 M.p. of the hydrochloride: 197 to 200°C.

Prepared from 2-nmino-N-isopropyl-3-trifluoromethyl-benzyInmine and iodosobenzene dichloride analogously to Example 12.

Example 261 15 2-Amino-5-chloro-N .N-diethyl-3-trifluoromethy1-benzylamine M.p. of the hydrochloride: 197 to 198°C.

Prepared from 2-nmino-N ,N-diethyl-3-trifluoromethyl-benzyInmine and iodosobenzene dichloride analogously to Example 12. 20 Example 262 N-(2-Amino-5-chloro-3-trifluoromethy1-benzy1)-hexamethylene-amine M.p. of the hydrochloride: 12H to 130°C. - 113 - 4 014 6 Prepared from N-(2-amino-3-trifluoromethy1-benzy1)-hexamethyleneamlne and iodosobenzene dichloride analogously to Example 12.

Example 263 N-Ethy1-2-amino-5-chloro-N-cyclohexyl-3-trifluoromethy1- benzylamine M.p. of the hydrochloride: 202 to 205°C.

Prepared from N-ethyl-2-amino-N-cyclohexyl-3-trifluoromethy1-benzylamine and iodosobenzene dichloride analogously to Example 12.

Example 264 2-Ami no-5-chloro-N-methyl-N-(morpholino-carbony1-methyl)- 3-trifluoromethyl-benzylamin e M.p. of the hydrochloride: 200 to 207°C (decomp.). Prepared from 2-amino-N-methyl-N-(morpholino- corbony 1 -inelhy 1)- 3-1 r i f luoromethy I -benzy lami ne and i odoso-benzcne dichloride analogously to Example 12.

Example 265 N-(2-Amino-3-bromo-5-fluoro-benzy1)-pyrrolidine M.p. of the dihydrochloride: 173 to 175°C (decomp.). Prepared from 2-amino-3-bromo-5-fluoro-benzyl alcohol, thionyl chloride and pyrrolidine analogously to Example 1. - 134 - 40146 Example 2bb 2-Amino-3-bromo-5-fluo ro-N-(trans-4-hydroxy-cyclohexy1)-benzylamine M.p. of the hydrochloride: 237 to 239°C (decomp.). Prepared from 2-amino-3-bromo-5-fluoro-benzy1 alcoholf thionyl chloride and trans-4-hydroxy-cyclohexyl-amine analogously to Example 1.

Example 267 2-Benzoylamino-3-bromo-5-carbethoxy-N,N-diethy1- benzyInmine M.p. of the hydrochloride: 220 to 222°C.

Prepared from 2-ainino-3-bromo-5-carbethoxy-N ,N-diethyI-benzylamine and benzoyl chloride in a benzene solution analogously Lo Example 22.

Example 2b8 3-Bromo-5-carbethoxy-2-(4-chloro-benzoylamino)-N ,N-diethyl-benzylamine M.p. of the hydrochloride: 1K7 to 193°C.

Prepared from 2-nmino-3-bromo-5-carbethoxy-N ,N-diethy1-benzylamine and 4-chloro-benzoyl chloride in a benzene solution analogously to Example 22. - 135 - 40146 Example 269 2-Acetamino-5-carbomethoxy-N.N-diethylbenzylamine 3.4 g of 2-acetamino-5-carbomethoxy-benzyl bromide were dissolved in 125 ml of chloroform and after adding 35 of diethylamine were left to stand for 15 minutes.

The mixture was evaporated to dryness in vacuo. The residue was dissolved in chloroform and the chloroform solution was extracted with dilute hydrochloric acid. The aqueous layer was made alkaline with anmonia and again extracted with chloroform. This chloroform extract was dried over sodium sulfate. The residue consisting of 2-acetamino-5-carbomethoxy-N ,N-diethyl-benzylnminc (m.p.: 77 to 80°C) was converted into the hydrochloride of m.p. 211 to 214"C with methanolic hydrochloric acid. Example 270 % 2-Amino-3-bromo-5-carbomethoxy-N,N-diethy1-benzylamine A solution of 1.1 g of bromine in 2 ml of acetic acid was added drop by drop whilst stirring at room temperature to a solution of 1.6 g of 2-amino-5-carbomethoxy-N ,N-diethyl-benzy lamine in 27 ml of acetic acid and 3 ml of water. The mixture was allowed to stand for 1 hour, poured onto ice, made alkaline with amnonia and - J 36 - 40146 extracted with chloroform. The chloroform solution was dried over sodium sulfate and evaporated to dryness in vacuo. The residue was dissolved in acetone and the 2-amino-3-bromo-5-carbomethoxy-N ,N-diethyl-benzylamine hydrochloride of m.p. 180 to 181WC was precipitated with ethereal hydrochloric acid.

Example 271 2-Amino-5-carbomethoxy-N tN-dlethy1-benzylamine 2.5 g of 2-acetamino-5-carbomethoxy-N,N-diethyl-benzylnmine were heated to boiling for 30 minutes with 50 ml of methanol and 15 ml of concentrated hydrochloric acid. The mixture was poured onto ice, made alkaline with anmonia and extracted with chloroform. The chloroform solution was dried over sodium sulfate, evaporated in vacuo and 2-amino-5-carbomethoxy-N,N-diethyl-benzylamino hydrogen fumarate of m.p. 177 to 179°c was obtained from the residue by dissolving in methanol and adding a solution of fumaric acid in ether.

Example 272 N-Ethy l-2-amino-3-broino-5-carboxy-benzylaminc 2.7 g of N-ethy1-2-amino-3-bromo-5-carbomethoxy-benzylamine were heated to boiling for 35 minutes with - 137 - 40146 65 ml of 6N hydrochloric acid. Whilst cooling to -15"C, N-ethy1-2-amino-3-bromo-5-carboxy-benzylamine hydrochloride crystallized out and was recrystallized from ethanol/ ether. 5 M.p. of the hydrochloride: 261°C (decomp.).

Example 273 2-Amino-5-bromo-N,N-dimethyl-3-fluoro-benzylamine 5.5 g of 2-amino-5-bromo-1-fluoro-benzy1 alcohol were dissolved in 150 ml of chloroform. Whilst stirring and 10 cooling with ice, 7.13 g (4.35 ml) of thionyl chloride were added, whereby a yellow precipitate was obtained. The suspension was left to stand overnight at room temperature and was then evaporated to dryness at room temperature by means of a rotation evaporator. The I r> crude benzyl chloridc thus obtained was suspended in 150 ml of chloroform. 20 ml of dimethylamine were added whilst stirring and cooling with ice, whereby a clear solution was obtained. This solution was allowed to stand for 30 minutes whilst cooling with ice and was then 20 extracted twice with saturated potassium carbonate solution.

The chloroform layer was washed with water, dried over sodium sulfate and evaporated to dryness in vacuo. The residue was taken up in absolute ethanol and acidified to - 138 - 40146 a pH of 3 with ethereal hydrochloric acid. The precipitated hydrochloride was suction filtered and dissolved in absolute ethanol. After addition of charcoal the solution was heated to boiling. After filtering off the 5 charcoal ond adding eLher, colorless crystals were obtained of m.p. 263 Lo 265°C (decomp.).

Example 274 2-Amino-5-bromo-N-cyclohexyl-3-fluoro-N-methy1-benzylamine M.p. of the hydrochloride: 226 - 228°C (decomp.). 10 Prepared from 2-amino-5-bromo-3-fluoro-benzyl alcohol, thionyl chloride and N-methyl-cyclohexylamine analogously to Kxainple 273.

Example 275 2-Amino-5-bromo-N-(trans-4-hydroxycyclohexyl)- 3-fluoro-15 benzylamine M.p. of the hydrochloride: 231 - 233°C.

Prepared from 2-amino-5-bromo-3-fluoro-benzyl alcohol , thionyl chloride and trans-4-hydroxy-cyclohexylamine analogously to Example 273. - 139 - 4 0116 Example 276 N-Ethyl-2-amino-5-bromo-N-cyclohexyl-3-fluoro-benzylamine M.p. of the hydrochloride: 193 to 195°C.

Prepared from 2-amino-5-bromo-3-fluoro-benzylamine, 5 thionyl chloride and N-ethy1-cyclohexylamine analogously to Example 273.

Example 277 N-(2-Aniino-5-carboxy-l>onzyl)-pyrrolldine M.p. of the hydrochloride: 193 to 194°C (decomp.). 10 Prepared from N-(2-amino-5-carbethoxy-benzyI)- pyrrolLdine and 6N hydrochloric acid analogously to Example 272.

Example 278 N-(2-Amino-3-bromo-5-carboxy-benzyl)-pyrrolidinc 15 M.p. of the hydrochloride: 267°C (decomp.).

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

Example 279 20 2-Amino-5-carboxy-N-(trans-4-hydroxycyclohexyl)-benzylamine M.p. of the hydrochloride: 224°C (decomp.).

Prepared from 2-amino-5-carbethoxy-N-(trans-4- - 140 - 4 0 116 Example 283 N-(2-Amino-5-carboxy-benzyl)-hexamethyleneamine M.p. of the dihydrochloride: >121°C (decomp.). Prepared from N-(2-amino-5-carbethoxy-benzyl)-hexamethyleneamine and 6N hydrochloric acid analogously to Example 272.

Example 284 N-(2-Ainlno-3-bromo-5-carboxy-benzyl)-hexamethyleneamine M.p. of the hydrochloride:>224°C (decomp.).

Prepared from N-(2-amino-3-bromo-5-carbethoxy-benzy 1) -hexamethy leneamine and 6N hydrochloric acid analogously to Example 272.

Example 285 2-Anuno-5-carboxy-N-(cis-3-hydroxycyclohexyl)-benzylamine M.p. of the dihydrochloride: 162°C (decomp.). Prepared from 2-amino-5-carbethoxy-N-(cis-3-hydroxycyclohexyl)-benzylamine and 6N hydrochloric acid analogously to Example 272.

Example 286 2-Amino-3-bromo-5-carboxy-N-(cis-3-hydroxycyclohexy1)- benzylamip.e M.p. of the hydrochloride: 119°C (decomp.).

Prepared from 2-amino-3-bromo-5-carbethoxy-N-(cis-3- - 142 - hydroxycyclohexyl)-benzylamine and 6N hydrochloric acid analogously to Example 272.

Example 287 2-Acetamino-5-bromo-N,N-dimethy1-3-dimethylamino-methy1-benzylamine 12 g of 4-bromo-2,6-dimethyl-acetanilide were dissolved in 1.9 1 of tetrachloromethane and heated to boiling. The solution was irradiated with UV-light and 15.8 g of bromine were added dropwise over 50 minutes.

After cooling to room temperature, 60 ml of dimethylamine were added and the solution was allowed to stand overnight, extracted twice with water, dried over sodium sulfate and evaporated to dryness in vacuo. The residue was dissolved in ethanol and the solution was acidified with ethanolic hydrochloric acid; 2-acetamino-5-bromo-N,N-dimethy1-3-dimethylamino-methy1-benzylamine dihydrochloride of m.p. 291°C (decomp.) crystallized out.

Example 288 4-Bromo-2,6-bis-(pyrrolidino-methyl)-acetanilide M.p. of the dihydrochloride: 319°C (decomp.).

Prepared from 4-l>romo-2,6-dimethyl-acetanilide, bromine and pyrrolidine analogously to Example 287. - 143- 146 Example 289 4-Bromo-2,6-bis-(piperidino-methyl)-acetanillde M.p. of the dihydrochloride: 308 to 312°C (decomp.). Prepared from 4-bromo-2,6-dimethyl-acetanilide, bromine and piperidine analogously to Example 287.

Example 290 4-Bromo-2,6-bi s- (mo rpho1ino-methy1)-acetan i1i d c M.p. of the dihydrochloridc: 283 to 284°C (decomp.). Prepared from 4-bromo-2,6-dimethyl-acetanilide , bromine and morpholine analogously to Example 287.

Example 291 2-Amino-5-bromo-3-dimethy laminomethy 1-N ,N-dimethy 1- benzylamine M.p. of the dihydrochloride: 284 to 287°C (decomp.). Prepared from 2-acetamino-5-bromo-3-dimethylamino-methyl-N ,N-dimethy1-benzylamine and hydrochloric acid analogously to Example 271.

Example 292 4-Bromo-2 ,6-bis-(piperidino-methyl)-aniline M.p. of the dihydrochloride: 283 to 286°C (decomp.). Prepared from 4-bromo-2,6-bis-(piperidino-methyl)-acetanilide and hydrochloric acid analogously to Example 271. - 144 - 4 0116 Example 293 4-Bromo-2,6-bis-(morphollno-methyl)-aniline M.p. of the dihydrochloride: 251 to 257°C (decomp.). Prepared from 4-bromo-2,6-bis-(morpholino-methyl)-r> acctanilide and hydrochloric acid analogously to Example 271.

Example 294 5-Acetyl-2-amino-3-bromo-N-(trans-4-hydroxycyclohexy1)-benzy lamine I(i M.p. of the hydrochloride: 214 to 216°C (decomp.).

Prepared from 5-acetyl-2-amino-3-bromo-benzyl bromide and trnns-4-hydroxy-cyclohexylamine analogously to F.xamplt- 2f>9. 145 - 4 0116 Example 205 5-Acetyl-2-araino-3-chloro-N-(trans-4-hydroxycyclohexyl)- benzylamine M.p. of the hydrochloride: 192 to 194°C (decomp.). Prepared from 4-acetamino-2-amino-3-chloro-benzyl bromide and trans-4-hydroxycyclohexylamine analogously to Example 269.

Example 20(> 2-Anii no-5-bromo-N-[ 1,3-dihydroxy-2-methyl-propyl- (2) ]- 3- trifluoromethy1-benzylamine M.p. of the hydrochloride: 22b to 228°C (decomp.). Prepared from 2-amino-N-Ll,3-dihydroxy-2-mcthyl-propyl-(2)]-3-trifluoromethyl-benzylamine and bromine analogously to Example 270.

Example 297 2-Amino-N-[1,3-dihydroxy-2-methyl-propy1-(2)]-3-trifluoro- methy1-benzylamine M.p.: 110 to 112°C..

Prepared from 2-amino-3-trifluoromethyl-benzyl chloride and 2-amino-2-methyl-l,3-propandiol analogously to Example 269. - 146 - 40146 Example 298 2-Amino-5-bromo-N-(cis-3-hydroxy-cyclohexyl)-3-trifluoro-methy1-benzylamine M.p. of the hydrochloride: > 70°C (decomp.).

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-trifluoromethy1- benzy Limine M.p. of the hydrochloride: 196 to 200°C.

Prepared from 2-nmino-3-trifluoromethyl-benzyl chloride and cis-3-hydroxy-cyclohexylamine analogously to Example 209.

Example 300 2-Amino-5-bromo-N-(hydroxy-tert.-butyl)-3-trifluoromethy1-benzylamine M.p. of the hydrochloride: 226 to 228°C (decomp.). Prepared from 2-nmino-N-(hydroxy-tert.-butyl)-3-trifluoromethyl-benzylamine and bromine analogously to Example 270. - 147 - 146 Example 301 2-Amino-5-bromo-N-(trans-4-hydroxy-cyclohexy1)-3-t ri fluoromethyl-benzylamine M.p. of the hydrochloride: 233 to 236°C (decomp.). Prepared from 2-amino-N-(trans-4-hydroxy-cyclohexyl)- 1-trifluoromethyl-benzylamine and bromine analogously Lo Example 270.

Example 102 2-Amino-N-(trans-4-hydroxy-cyclohexyl)-3-trifluoromethy1-benzylamine M.p. of the hydrochloride: 228 to 230°C (decomn.). Prepared from 2-amino-3-trifluoromethyl-benzy1 chloride and trans-4-hydroxy-cyclohexylamine analogously Lo Example 269.

ExampIv 101 2-Amino-N-(hydroxy-tert.-butyl)-3-trifluoromethy1- benzylamine M.p.: 110 to 112°C.

Prepared from 2-amino-3-trifluoromethyl-benzyI chloride and hydroxy-tert.-butylamine analogously Lo Example 269. - 148 - 40146 Example 304 2-Amino-5-chloro-N,N-dimethy1-3-trifluoromethy1-benzylamine M.p. of the hydrochloride: 210 to 212°C (decomp.). Prepared from 2-amino-3-trifluoromethyl-benzylamine and lodosobenzene dichloride analogously to Example 270. Example 305 2-Amino-5-bromo-N ,N-dimethy1-3-trifluoromethyl-benzylamine M.p. of the hydrochloride: 184 to 185°C.

Prepared from 2-amino-N,N-dimethyl-3-trifluoromethyl-benzylamine and bromine analogously to Example 270.

Example 306 N-Ethyl-2-amino-5-carbethoxy-benzylamine 3.8 g of N-ethyl-2-amino-N-benzyl-5-carbethoxy-benzylaminc were hydrogenated in 50 ml of methanol and 1 ml of concentrated hydrochloric acid at room temperature and at a hydrogen pressure of 5 atmospheres in the presence of palladium on charcoal. The catalyst was filtered off and the filtrate was evaporated to dryness in vacuo. The residue recrystallized from ethanol solution on addition of ether. N-Ethy1-2-amino-5- - 149 - 116 carbethoxy-benzylamine hydrochloride was obtained of m.p. 173 to 176°C (decomp.).

Example 307 3-Bromo-2-butyrylamino-5-carbethoxy-N,N-diethy1- benzylamine 3 g of 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine were dissolved in 30 ml of benzene and heated for 30 minutes with 3 ml of butyryl chloride at 50°C. The mixture was evaporated to dryness in vacuo and the residue was purified by chromatography with silica gel (elucnt: benzene: ethyl acetate = b:l); 3-bromo-2-butyryl-ainino-5-carbethoxy-N ,N-diethyl-benzylamine was obtained* which was converted into the hydrochloride of m.p. 134°C with ethanolic hydrochloric acid.

Example 308 N-Ethyl-2-amino-N-benzyl-5-carbethoxy-benzylamine M.p. of the hydrochloride:^ 61°C (decomp.).

Prepared by reaction of 2-acetamino-5-carbethoxy-benzyl bromide and N-ethylbenzylamine analogously to Example 2(>9 and then reacting the crude 2-acetamino-N-cthyl-N-benzyl-5-carbeLhoxy-benzyl-amine thus obtained with ethanol/hydrochloric acid analogously to Example 271. - 150 - 40146 Example 309 N-( 2-Ace tamino- 5-carbethoxy-benzy 1) -pyrrolidine Oil, homogeneous by chromatography. i Prepared from 2-acetamino-5-carbethoxy-benzy1 bromide 5 and pyyrolidine analogously to Example 269.

Example 310 N-(2-Amino-5-carbethoxy-benzyl)-pyyrolidine M.p. of the dihydrochloride: 146 to 149°C.

Prepared from N-(2-acetamino-5-carbethoxy-benzyl)-10 pyrrolidine and ethanol/hydrochloric acid analogously to Example 271.

Example 311 N-(2-Amino-3-bromo-5-carbethoxy-benzyl)-pyrrolidine M.p. of the hydrochloride: 204 to 205°C. 15 Prepared from N-(2-amino-5-carbethoxy-benzyl)- pyrrolidine and bromine analogously to Example 270.

Example 312 2-Amino-5-carbethoxy-N-(trans-4-hydroxycyclohexyl)-benzylamine 20 M.p. of the hydrochloride: 237°C (decomp.).

Prepared by reacLion of 2-acetamino-5-carbethoxy- - 151 - benzyl bromide and trans-4-hydroxycyclohexylamine analogously to Example 269 followed by reaction of the 2-acetamino-5-carbethoxy-N-(trans-4-hydroxy-cyclohexyl)-benzylamine thus obtained with ethanol/hydrochloric acid analogously to Example 271.

Example 313 2-Ami no-3-bromo-5-carbethoxy-N-(trans-4-hydroxycyclo-hexy1)-benzylamine M.p. of the hydrochloride: 137°C (decomp.).

Prepared from 2-amino-5-carbethoxy-N-(trans-4-hydroxycyclohexyl)-benzylamine and bromine analogously to Example 270.

Example 314 2-Acetamino-3-bromo-5-carbethoxy-N-cyclohexy1-N-methy1- benzylamine M.p. of the hydrochloride: 220 to 223°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-N-cyclohexyl-N-methyl-benzylamine and acetyl chloride analogously to Example 307. - 152 - 40146 Example 315 N-( 2-Amino-5rcarbethoxy-benzvl)-morpholine M.p. of the hydrochloride: 205°C (decomp.).

Prepared by reaction of 2-acetamino-5-carbethoxy-benzyl bromide and morpholine analogously to Example 269 followed by reaction of the N-(2-acetamino-5-carbethoxy-bcnzyl)-morpholine thus obtained with ethanol/hydrochloric acid analogously to Example 271.

Example 316 N-(2-Amino-3-bromo-5-carbethoxy-ben2yl)-morpholinc M.p. of the hydrochloride: 221°C (decomp.).

Prepared from N-(2-amino-5-carbethoxy-benzyl)-morpholine and bromine analogously to Example 270.

Example 117 N-(2-Aini no-5-carbclhoxy-benzy 1 )-hexamethylencainl nc M.p. of the hydrochloride: 108 to 169°C.

Prepared from N-(2-acetamino-5-carbethoxy-benzyl)-hexamcthyleneamine and ethanol/hydrochloric acid analogously to Example 271. - 153 - 4 0 116 Example 318 N-(2-Amino-3-bromo-5-carbethoxy-ben2yl)-hexamethyleneamine M.p. of the hydrochloride: 219 to 221aC.

Prepared from N-(2-amino-5-carbethoxy-benzy1)-hexamethyleneamine and bromine analogously to Example 270. Example 319 2-Acetainino-N-benzyl-5-carbethoxy-N-tert.-buty I - benzyIami nc M.p. of the hydrochloride: 208°C (decomp.).

Prepared from 2-acetamino-5-carbethoxy-benzy1 bromide and N-tert.-butyl-benzylamine analogously to Example 2b9. Example >20 2-Am i no-5-carbethoxy-N-(c i s-3-hyd roxycyclohexyI)- benzylamine M.p. of the hydrochloride: 201 to 203°C.

Prepared by reaction of 2-acetamino-5-carbethoxy-benzyl bromide and cis-3-hydroxycyclohexylamine analogously to Example 269 followed by reaction of the 2-acetamino-5-carbethoxy-N-(cis-3-hydroxy-cyclohexyl)-benzylamine thus obtained with ethanol/hydrochloric acid analogously to Example 271. - 154 - 40140 Example 321 2-Amlno-3-b?orao-5-carbethoxy-N-(cis-3-hydroxycyclohexyl)-benzylamine M.p. of the hydrochloride: 103°C (decomp.). 5 Prepared from 2-amino-5-carbethoxy-N-(cis-3-hydroxy- cyclohexyl)-benzylamine and bromine analogously to Example 270.

Example 322 2-Amino- 5-carbomethoxy-N- (trans-4-hydrocycyc lohexy 1) -10 benzylamine M.p. of the fumarate: 221°C (decomp.).

Prepared by reaction of 2-acetamino-5-carl>omethoxy-benzyl bromide and Lrans-4-hydroxycyclohexylamine analogously to Example 2(>0 followed by reacLion of the 15 2-accLam!no-5-carbomethoxy-N-(trans-4-hydroxycyclohexyl)- benzylamine thus obtained with methanol/hydrochloric acid analogously to Example 271.

Example 323 2-Amino-N ,N-diethyl-5-isopropoxy-carbonyl-benzylamine 20 M.p. of the hydrogen fumarate: 158°C.

Prepared by reaction of 2-acetamino-5-isopropoxy- carbonyl-benzyl bromide and diethylamine analogously to Example 269 followed by reaction of the 2-acetamino-N,N- - 155 - 4 0116 dlethyl-5-isopropoxy-carbonyl-benzylamine thus ohLalned with isopropanol/hydrochloric acid analogously to Example 271.

Example 324 5 2-Acetamino-N-benzy 1-5, N-dimethy 1-benzy lamine The substance is an oil; proof of structure by UV-, NMR- and IR- spectra.

Prepared from 2-acetamino-5-methyl-benzyl bromide and N-methy 1-benzy lamine analogously to Example 2(>9. 10 Examp It' 325 N-KLhy I - 2-am i no- 3- bromo- 5-ca rboLhoxy-benzy lam i iu-M.p.: 199 to 20I°C.

Prepared from N-ethy1-2-amino-5-carbethoxy-benzylamine nnd bromine analogously to Example 270.

I r» Example 32b 4-Bromo-2tb-bis-(pyrroiidino-methyl)-aniline M.p. of the dihydrochloride: 274 to 276°C (decomp.). Prepared from 4-bromo-2,6-bis-(pyrrolidino-methyl)-acetanilide and hydrochloric acid analogously to 20 Example 271. - 156 - 40146 Kxamplc 127 2-Aml no- l-bromo-N-( L r.iiis-4-hydroxy-cyc 1 ohoxy I )-5-methoxy- Ainorphous, proof of structure by IR-, UV- and NMR-5 spectra.

Prepared from 2-,-unino-3-bromo-5-methoxy-bcnzyl alcohol, thionyl chloride and trans-4-hydroxycyclohexylamine analogously to Example 273.

Example 128 10 N-Ethy1-2-amino-3-bromo-N-cyclohexyl-5-methyl-tx-nzylamine 4.4 g of 2-amino-3-bromo-5-methyl-benzyl alcohol were heated for 5 hours at 165°C with 1.5 g of propionic acid and 3 g of N-ethyl-cyclohexylamine. The mixture was evaporated to dryness iji vacuo. The residue was lr> dissolved in ether and the solution was extracted twice with water, dried and evaporated to dryness in vacuo. The residue was purified by chromatography over silica gel (eluent: chloroform-ethyl acetate = 6:1). The eluatc was evaporated, taken up in isopropanol and the 20 hydrochloride of m.p. 184 to 186°C was brought to crystallization with hydrogen chloride. - 157 - 40146 Kx.-imptc 32') N-Klhy I- 2-ain i no- 3-bromo-5-carboxy-N-cyc lohexy I - benzylamine . ) g of 2-amino-3-bromo-5-carboxy-benzyJ alcohol r> wore honied for 5 hours at 140°C with 3 g of N-i>lhyl- cyclohexylamine and 1.5 g of butyric acid. The mixture was evaporated in vacuo and the residue was purified by chromatography over silica gel with methanol as eluent. The hydrochloride of m.p. 227 to 229°C (decomp.) was I') obtained from the eluale with hydrochloric acid.

Example 330 2-Amino-3-bromo-5-carbethoxy-N ,N-diethyl-benzylamine 2.7 g of 2-amino-1-bromo-5-carbethoxy-benzy1 alcohol were heated in an autoclave for 5 hours at 150°C with 3 g 1 r> of diethylamine and 2 g of butyric acid. The mixture was evaporated in vacuo and the residue was purified by chromatography over silica gel with toluene/acetone = 4:1 as eluent. The hydrochloride of m.p. 165 to 168°C was oblained from the eluate with ethereal hydrochloric 20 acid. 40146 Example 331 N-EthyI-2-amino-3-bromo-5-catboxy-N-cyclohexy1-benzylamine 2.4 g of 2-amino-3-bromo-5-carboxy-benzyl alcohol were heated for 5 hours at 150°C with 3.3 g of N-ethyl-cyclohexylamine and 0.1 g of magnesium oxide. The product obtained was subsequently distributed between chloroform and water. The chloroform layer was dried and evaporated to dryness. The hydrochloride of m.p. 227 to 220°C (decomp.) was crystallized by dissolving the residue in ethanol and adding ethereal hydrochloric acid.

Example 332 2-Amino-3-bromo-5-carbethoxy-N tN-diethy1-benzylamine 2.7 r of 2-amino-J-bromo-5-carbethoxy-benzyl alcohol were heated in an autoclave for 5 hours at 150 to lf>0uC with 2.4 £ of diethylamine and 0.2 g of magnesium oxide. The mixture was evaporated JUi vacuo and the residue was purified by column chromatography over silica gel with toluene-acetone (4:1). The hydrochloride of m.p. 165 to lb8°C was obtained from the eluate with ethanol/ - 159 - 40 146 hydrochloric acid.

Example 333 N-F.thy l-2-amlno-3-bromo-5-carboxy-N-cyclohexyl-benzylaminc 2.5 g of 2-amino-3-bromo-5-carboxy-benzyl alcohol were heated for 5 hours at 150"C with 4 g of N-ethyl-cyclohexylamine and 0.1 g of sulfuric acid. The excess of N-ethyl-cyclohexy lamine was distilled off _ijn vacuo nnd Lhe residue was distributed between chloroform and dilute ammonia. The chloroform solution was dried and evaporated Lo dryness; the residue was purified by chromaLography over silica gel with methanol and Lhe hydrochloride of m.p. 227 to 229"C (decomp.) was cryst.nl li zed from the eluate by addition of ethereal hydrochloric acid.

KxampIe 334 2-Amino-3-bromo-5-carbsthoxy-N,N-dlethy1-benzylamine 2.7 g of 2-amino-3-bromo-5-carbethoxy-benzy1 alcohol were heated in an autoclave for 5 hours at 150 to 160°C. with 2.4 g of diethylamine and 0.1 g of sulphuric acid. The mixture was evaporated jrt vacuo and the residue was distributed between chloroform and dilute ammonia. The 160 4 0116 chloroform phase was separated and the solvent was evaporated. ( The residue was purified by chromatography over silica gel with toluene-acetone (4:1) as eluent. The hydrochloride of m.p. 165 Lo 1(>8°C was obLained from r» Lhe evaporation residue of the eluaLe with ethanolic hydrochloric acid.

Example 335 N-KLhy1-2-amino-3-bromo-5-carboxy-N-cyclohexyl-benzylamine 2.0 g of 2-aceLainlno-3-bromo-5-carboxy-bcnzyI H) alcohol were stirred for 4 hours at 175°C with 1.5 g of N-ethyl-cyclohexy limine In 20 ml of Letraline. The soluLion was evaporaLed Lo dryness in vacuo; Liu- residue was dislributed between chloroform and water. The ■ iiloroform phase was separated and was evaporaLed Lo I'» dryness. The residue was purified by chroma Lography over silica gel wlLli methanol. The hydrochloride of in.p. 227 Lo 220°C (decomp.) was obLained from the eluate by addition of ethereal hydrochlqric acid. - 161 - 4 0116 Examp1c 33b 2-Amino-3-bromo-5-carbethoxy-N.N-diethy1-benzylamine 3.1 g of 2-acetamino-3-bromo-5-carbethoxy-benzyl alcohol were heated in an autoclave for 5 hours ;it 150 rt to 170UC with 2.4 g of diethylamine. The mixture was evaporated and the residue was purified by chromatography over silica gel with toluene-acetone (4:1) as eluent. The hydrochloride of m.p. 165 to 168°C was obtained from the eJuate with ethanolic hydrochloric acid. 10 Example 337 2-Amino-1-bromo-5-carbethoxy-N,N-diethyl-benzylaminc l g of ethyl 3-acetoxymethyl-4-amino-5-bromo-benzoatc was heated In an autoclave for 2 hours at 120°C with 5 ml of diethylamine. After cooling to room temperature, 15 the reaction mixture was evaporated to dryness In vacuo and the residue was purified by chromatography over silica gel (eluent: toluene: acetone = 4:1). The hydrochloride of m.p. Ib5 to 168°C was obtained from the eluate by means of hydrogen chloride. - 162 - 40146 Example UK N-Ethy 1-2-amlno-3-browo-5-carboxy-N-cyclohexyl-benzy ltnnlne 2.8 g of 3-acetoxymethyl-4-amino-5-bromo-benzole acid were heated for 5 hours at 120 to 130"C with 5 g of N-ethyl-cyclohexylamine. The mixture was evaporated to dryness in vacuo and the residue was purified by chromatography over silica gel with methanol as eluent. The hydrochloride of m.p. 227 to 229WC (decomp.) was obtained from the eluate with t-Lhereal hydrochloric acid.

Examp I e 3 3*> 2-Amino-3-bromo-5-carbethoxy-N,N-diethy1-benzylamine 2.7 g of 2-amlno-3-bromo-5-carbethoxy-benzy1 alcohol and 0.5 g of sodium hydride in 100 ml of absolute ether and 50 ml of absolute tetrahydrofuran were refluxed for 6 hours. The mixture was cooled to -70°C, 1.7 g of toluene sulfonyl chloride in 30 ml of ether were slowly added. The mixture was allowed to warm up to -10°C whilst sLlrring and was then again cooled to -70°C and 1.4 g of diethylamine were added. The cooling bath was removed and the mixture was stirred until room temperature - 163 - 40146 was readied. The mixture was then extracted wlLh water. The organic layer separated and evaporated in vacuo and the residue was purified by chromatography over silica gel with toluene/acetone (4:1). The hydrochloride of m.p. 165 to 168°C was obtained from the eluate with hydrochloric acid.

ExampIe 140 N-Ethy1-2-amino-3-bromo-5-carboxy-N-cyclohexy1-benzylamine 3.2 g of (2-amino-3-broino-5-carboxy-benzyl)-ethyl ether and 13.7 g of N-ethy1-cyclohexylamine were heated for 5 hours at 200°C in the presence of acidic aluminium oxide. The reaction mixture was subsequently distributed between water and chloroform. The chloroform layer was washed with water, dried and evaporated. The residue was purified by chromatography over silica gel wiLh methanol. The hydrochloride of m.p. 227 to 229°C (decomp.) was obtained from the eluate with hydrochloric acid.

Example 341 2-Amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine 3.5 g of (2-amino-3-bromo-5-carbethoxy-benzy1) - 164 - 40146 phenyl ether and 6 ml of diethylamine In the presence of acidic aluminium oxide were heated in an autoclave for 5 hours at 180 to 200"C. The mixture was evaporated. The residue was distributed between chloroform and water 5 and the chloroform layer was separatee^ dried and evaporvilrtl. The residue was purified by chrouuil o^mphy over si lien gel with toluene-acetone (4:1). The hydrochloride of m.p. 165 to 168"C was obtained by addition of ethanolic hydrochloric acid to the eluate. 1() Example 342 N-Ethy1-2-amino-3-broino-5-carboxy-N-cyclohexy1-benzylamine 4.7 g of N-(2-amino-3-bromo-5-carboxy-benzy1)-N,N-diethyl-inethyl-amnonium Iodide were heated for 1 hour at 150°C with 10 g of N-ethyl-cyclohexylamine. The excess lr> of N-cthyl-cyclohexylamine was distilled off in vacuo and the residue was distributed between chloroform and diluted ammonia. The chloroform layer was washed with water, evaporated and the residue was converted into the hydrochloride of m.p. 227 to 229°C (decomp.) by 20 dissolving in ethanol and adding ethereal hydrochloric acid. - 165 - Example 343 2-Amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine 4.4 g of N-(2-amino-3-bromo-5-carbethoxy-benzyl)-trimelhyl-amnoniura iodide were heated in an autoclave for 1 hour at 150 to 170"C with 10 g of diethylamine. The mixture was evaporated in vacuo. The residue was distributed between chloroform and water and the chloroform phase was evaporated. The residue was purified by chromatography over silica gel with toluene/acetone (4:1) as eluent. The hydrochloride of m.p. 165 to 168°C was obtained from the eluate with ethanolic hydrochloric acid.

Example 344 2-Amino-3-bromo-5-carbethoxy-N,N-diethy1-benzylamine 2 g of 3-bromo-5-carbethoxy-N,N-diethyl-2-nitro-bcnzylainine were dissolved In 20 ml of ethanol and hydrogenated at room temperature and at a hydrogen pressure of 5 atmospheres in the presence of 0.2 g of Rancy-nlckel. The catalyst was then filtered off and the mixture was evaporaLed to dryness j_n vacuo. The residue was purified - 166 - 40146 by chromatography over silica gel (eluent: chloroform: ethyl acetate - 6:1) and the base was converted into the hydrochloride of m.p. 165 to 168°C.

Example 345 2-Amino-3-bromo-5-carbethoxy-N ,N-diethyl-benzylamine 0.9 g of N-ethyl-2-amino-3-bromo-5-carbethoxy-benzylamine were heated for 15 minutes whilst stirring with 0.4 ml of diethylsulfnte and 0.4 ml of 30% sodium hydroxide solution at 90°C. After cooling to room temperature, the mixture was extracted twice with chloroform; the chloroform extract was washed once with dilute sodium hydroxide solution and twice with water and after drying over sodium sulfate was evaporated to dryness in vacuo. The residue was taken up in isopropanol and converted into 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine hydrochloride with isopropanollc hydrochloric acid.

M.p.: 165 to 168°C.

Example 346 N-Ethy1-2-amino-3-bromo-5-carboxy-N-cyclohexy1-benzylamine 2.5 g of 2-amino-3-bromo-5-carboxy-benzaldehyde were - 167 - healed for 8 hours at 100**C with 8.5 g of N-ethy1-cyclohexylamine and 3.2 g of formic acid. The mixture was evaporated to dryness in vacuo and the residue was purified by chromatography over silica gel (eluent: methanol). The hydrochloride of m.p. 227 to 229°C (decomp.) was obtained from the eluate by addition of hydrochloric acid.

Example 347 2-Ami no-3-l>romo-5-carbeLhoxy-N ,N-dielhyl-benzyIamine 2.7 k of 2-ainino-3-bromo-5-carbethoxy-benzaldehyde, r> % of diethylamine and 3 g of formic acid were heated for (> hours at 120°C. The reaction mixture was distributed between dilute ammonia and chloroform; the chloroform I oyer was dried, evaporated to dryness and the residue was purified by chromatography over silica gel (eluent: I olui-nciacfl one = 4:1). The hydrochloride of m.p. I(>r» Lo l(»swc wns ohlaincd from lhe eluate by addition of hydrogen chloride In clhanol. 1 <>H - 40146 Example 348 2-Amino-3-bromo-5-carboxy-N-cyc lohexy 1-benzy lamine 3.5 g of N-(2-amino-3-bromo-5-carboxy-benzylidene)-eye lohexy lamine and 0.4 g of sodium hydroxide were dissolved in 30 ml of absolute ethanol and stirred for 5 hours with 0.5 g of sodium borohydride. The excess of sodium borohydride was destroyed by addition of hydrochloric acid until a pH value of about 3 was reached. The mixture was evaporated to dryness in vacuo and the residue was distributed between chloroform and dilute amnonia. The chloroform layer was evaporated to dryness, the residue was dissolved in ethanol and the dihydrochloride of m.p. 261 to 262°C (decomp.) was brought to crystallization by addition of ethereal hydrochloric acid.

Example 149 2-Ami no- 3-bromo- 5-carboxy-N-cyc lohexy 1-N-methy 1- benzy lamine 2.5 g of 2-amino-3-bromo-5-carboxy-benzy1 alcohol and 15.3 g of N,N* ,N"-tricyclohexyl-N,N' ,N"-trimethyl-phosphoric acid-triamide were heated for 1 hour up to 210°C. The mixture was cooled and was then distributed between chloroform and dilute hydrochloric acid. The - 169 - 40 146 acidic solution was filtered through charcoal, made alkaline with ammonia and extracted with chloroform. The chloroform extract was dried and the product was evaporated Lo dryness. The residue was dissolved In 1 ethanol and the hydrochloride of m.p. 230 to 240°(' was precipitnled by addition of ethereal hydrochloric acid. Kxample 150 2-Amino-3-bromo-5-carboxy-N-cyclohexy1-N-methy1-benzylamine 2.1 r of 2-amino-3-bromo-5-carboxy-benzyl alcohol I" and 10 v. of N-cyclohcxyl-N-methylacctamide were heated for *> hours at 170°C. The excess of amide was distilled off and Lhe residue was purified by chromatography over silica Re 1 wilh melhanol as cluenL. The hydrochloride «»f m.p. 2 JO Lo 240UC was oblained by addilion of i Lht real I '< hydrochloric acid and evaporation.

Kxample 351 2-Benzoylamlno-3-bromo-5-carbethoxy-N ,N-dielhy I - benzylamine 3.f> g of H-broino-6-carbethoxy-2-phenyl-4H-3 ,1-20 benzox.izine hydrobromide were heated in a autoclavc for - 170 - 40146 2 hours at 150 to 160"C with 4.4 g of diethylamine. The mixture was then evaporated to dryness in vacuo. The residue was distributed between chloroform and diluted amnonia, the chloroform layer was evaporated and the residue was dissolved in ethanol. The hydrochloride of m.p. 220 to 222°C was precipitated by addition of ethereal hydrochloric acid.

Example 152 N-Ethy1-2-amino-3-broino-5-carboxy-N-cyclohexy1-benzylamine 0.6 g of N-ethyl-2-amino-3-bromo-5-carbamoy1-N-cyclohexy 1-benzy lamine were dissolved in 45 ml of concentrated hydrochloric acid and boiled for 40 minutes. Whilst cooling, a precipitate was obtained which was suction filtered; the hydrochloride of m.p. 227 to 229°C (dccomp.) was obtained by recrystallization from ethanol.

Example 353 N-Ethy1-2-amino-3-broino-5-carboxy-N-cyclohexyl-benzylamine 1 g of N-ethyl-2-amino-3-bromo-N-cyclohexyl-5-cyano-benzylamine were boiled for 40 minutes with 45 ml of concentrated hydrochloric acid. The reaction mixture was - 171 - 40146 poured onlo ice, neutralized with ammonia and a small quantity of an insoluble material was removed by filtration. The filtrate was extracted with ether. The ether extract was evaporated to dryness. The hydrochloride of m.p. 227 to 229°C (decomp.) was obtained from the residue by dissolving it In ethanol and adding ethereal hydrochloric acid.

Example >54 2-Amino-l-bromo-5-carbethoxy-N tN-diethyl-benzylaininc I g of 2-amino- >-bromo-5-cyano-N ,N-diethy1-benzylami newt re dissolved in 50 ml of absoluLe elhanol. Th*. snlnl ion was saluraled with hydrogen chloride, refluxed for 10 hours and after addition of 5 ml of water for a further "j hours. The mixture was then evaporated Lo dryness in vacuo. The crude producL was convened into the Ixise and purified by chromatography over silica gel (cluenl: eLhyl aceLale). Afler evaporation of Lhe eluate, the residue obtained was converted into the hydrochloride of m.p. 165 to 168°C with isopropanolic hydrochloric acid. - 172 - 40146 Kxamplc 355 2-Amino-3-bromo-5-carbethoxy-N ,N-dlethy1-benzylamine 5 g of 2-amino-3-bromo-5-carboxy-N,N-diethyl-bcnzylamine were dissolved in 150 ml of absolute cLhanol. r> This solut ion was saturated with hydrogen chloride, refluxed for I hour and then evaporated to dryness _i_n vacuo. The hydrochloride of m.p. 165 to 168UC was obtained by crystallization of the residue from ethanol.

Kxample 356 10 2-Amino-3-bromo-5-carbcthoxy-N,N-diethy1-benzylamine 0.7 g of 2-amino-3-bromo-5-carbomethoxy-N,N-diethyl-benzylamine were dissolved in 75 ml of absolute ethanol , 0.02 g of sodium hydroxide were added and the mixture was refluxed for 15 minutes and evaporated to dryness vacuo. 15 The residue was distributed between water and chloroform.

The chloroform solution was dried and evaporated to dryness. The residue was converted into the hydrochloride of m.p. 165 to 168°C with ethereal hydrochloric acid. - 173 - Example 157 2-Amino-3-bromo-5-carbethoxy-N,N-diethy1-benzylamine 3 g of 2-amino-3-bromo-5-carboxy-N,N-diethyl-benzy laininc were heated with 9 inl of thionyl chloride in 30 ml of toluene for 1 hour at about 100QC. The mixture was evaporated to dryness in vacuo. The 4-araino-3-bromo-5-(N,N-diethyl)-aminomethyl-benzoylchloride hydrochloride thus obtained was sLirred for 3 hours with a solut ion of I g of sodium in 20 ml of absolute ethanol. Tlu» solution was evaporated to dryness jji vacuo. The residue was distributed between chloroform and water and Lhe chloroform solution was dried and evaporated Lo dryness. The hydrochloride of m.p. 165 to 168°C was obtained from the residue by dissolving in ethanol and adding ethereal hydrochloric acid.

Example 358 2-Amino- 3-bromo-5-cnrbeLhoxy-N ,N-di ethyl-benzy I.Mini nc I.I g of 2-amino- 3-bromo- 5-carbamoy 1-N ,N-di elliy I-benzylamine were dissolved in 30 ml of absolute ethanol. The solution was saturated with hydrogen chloride and boiled for 6 hours. The mixture was evaporated to dryness and the - 174 - 40140 residue was distributed between chloroform and dilute anmonia. The chloroform solution was evaporated and the residue was purified by chromatography over silica gel (eluent: toluene: acetone ■» 4:1). The hydrochloride 5 of m.p. 165 to 168WC was obtained from the evaporation residue of the eluate by dissolving in ethanol and adding ethereal hydrochloric acid.

Example "359 N-(2-Aniino-5-carboxy-benzy1)-hexamethy1eneamIne 10 M.p. of the dihydrochloride:^121°C (decomp.).

Prepared from 2-amino-5-carboxy-benzyl bromide and hexamethyleneamine analogously to Example 25.

Example 360 2-Amino-3-bromo-5-carbethoxy-N-cyclohexy1-N-mcthyl- I r> benzylamine M.p. of the hydrcchloride: 212 to 215°C.

Prepared from 2-amino-3-bromo-5-carbethoxy-benzy1 bromide and N-methyl-cyclohexylamine analogously to Example 25. - 175 - 40146 Example 361 2-Amino-3-bromo-5-carbethoxy-N-(trans-4-hydroxy-cyclohexy1)-benzylamine M.p. of the hydrochloride: 137°C (decomp.).

Prepared from 2-amino-3-bromo-5-carbethoxy-benzyl bromide and trans-4-hydroxy-cyclohexylamine analogously to Example 25.

Example 362 N-(2-Ami no-3-bromo-5-carbethoxy-benzyl)-hexamethyleneamine M.p. of the hydrochloride: 219 to 221"C.

Prepared from 2-ainino-3-bromo-5-carbethoxy benzyl bromide and hexamethyleneamine analogously to Example 25. Example 363 N-Ethy1-2-amlno-N-cyclohexyl-5-methy1-benzylami ne M.p. of the hydrochloride: 189 to 191°C (decomp.). Prepared from 2-amino-5-methyl-benzyl bromide and N-ethyl-cyclohexylamine analogously to Example 25.

ExampIe 364 2-Amino-3-bromo-5-cyano-N-cyclohexy1-N-methy1-benzylamine M.p. of the hydrochloride: 236 to 240°C.

Prepared from 2-ainino-3-bromo-5-cyano-benzy1 bromide - 176 - 40146 and N-methyl-cyclohexylamine analogously to Example 25. Example 365 • 2-Amino- 3-bromo-5-carbamoy1-N ,N-diethy1-benzylamine M.p.: 140 to 142°C.

Prepared from 2-amino-3-bromo-5-carbamoy1-benzyl bromide and diethylamine analogously to Example 25. Example 366 2-Amino-5-bromo-N ,N-diethyl-3-trifluoromethyl-benzylamine M.p. of the hydrochloride: 198 to 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-methy1-benzylamine M.p. of the hydrochloride: 177 to 179°C (decomp.). Prepared froin 2-amino-5-bromo-3-methyl-bcnzy1 bromide and diethylamine analogously to Example 25. 177 40146 KxampIe 168 N-Klhyl-2-oini no- 5-hromo-N-cyc lohexy 1- 1-me thy l-ben2y lam i nc M.p. of the dihydrochloride: 183 to 187"C (decomp).

Prepared from 2-amino-5-bromo-3-methyl-benzyl bromide and N-5 clhyI-eyelohexylamine analagously to Example 25.

Kxamp I e 36') N-( 2-Ami no-r>-bromo- 3-methy 1-benzy 1 )-hexamethyleneamine M.p. of the dihydrochloride: 159 to 164" (decomp.).

Prepared from 2-amino-5-bromo-3-methyl-benzyl bromide and 10 hexamethyleneamine analogously to Example 25.

KxampIe 370 2-Amino-5-bromo-4-tert.-buty1-N-cyclohexy1-N-methy1-benzyI-ami ne M.p. of the hydrochloride: 202 to 202.5"C (decomp.). 1 r> Prepared from 2-amino-5-broino-4-tert .-butyl-benzyl bromide and N-methyI-eyelohexylamine analogously to Example 25. Kxample )71 N-( 2-Amino-r>-bromo-4-tert. - butyl-benzy 1 )-morphol ine M.p. of the dihydrochloride: 194 to 198"C (decomp.). - 178 - 40146 Prepared from 2-amino-"i-bromo-A-tert. -butyl-benzyl bromide and morpholine analogously to Example 2r>.

Example 172 2-Amino-r»-bromo-N-( trans-4-hydroxy-cyc lohexy l)-N-me thy I - 3-5 /N-methyI- (trans-4-hydroxy-cyclohexylamlno)-methyl7-benzyl-amine M.p. 179 to 180 C.

Prepared from 2-amino-5-bromo-3-hydroxyinethyl-benzyl alcohol, ihionyl chl«»ride and N-methyl-trans-4-hydroxy-cyclohexyl-10 amine analogously to Example I.

Example 373 2-Amino-3-bromo-N.N-d imethyI-l-methoxy-benzylamine Oil; proof of structure by IR-, UV- and NMR-spectra.

Prepared from 2-amino-3-bromo-r>-methoxy-benzyl bromide and I r> dimcthylainine analogously Lo Example 2*>.

Example 374 N-( r>-Acetyl-2-amino-benzyl )-hexamethyleneamine M.p. of hydrochloride: 205 to 207°C (decomp.).

Prepared from 'j-acetyl-2-ainino-benzyl bromide and hexamethyl- - 179 - 40140 cne-nmlne analogously Lo Kxamplc 25.

KxampIe 175 5-Ace ty I-2-oini no-3-bromo-N. N-dlmethyl-bengy lamine M.p.: 92 to 95UC 5 Prepared from 5-acety 1-2-nm 1 no-3-bromo-benzyl bromide and dimethylntninc analogously to Example 25.

Kxamp le 37b 5-Acetyl-2-amlno-N.W-dimethy1-benzylamine M.p. of the hydrochloride: 209 to 215°C (decomp.). 10 Prepared from 5-acetyl-2-amlno-benzyl bromide and dimethyl-amine analogously to Example 25.

Kxainple 377 N-Kthyl-2-nini no-3-bromo-N-cvclohexy1-5-(l-hvdroxv-ethvl)-hcny.yl-amine 15 M.p. I 17 Lo 121'C Prepared from 2-amino-3-bromo-5-(l-hydroxyethyl)-benzyl bromide and N-ethyl-cyclohexylamine analogously to Example 25. Example 378 2-Amino-1-hromo-5-carbethoxy-N.N-diethyl-benzylamine - 180 - 40146 M.p. of the hydrochloride: 165 to 168"C.

Prepared from 2-amlno-3-bromo-S-carbethoxy-benzyl-pyridinium bromide and diethylamine analogously to Example 343.

Kx.-nnple 170 N-KthyI-2-amino-3-carboxy-N-cyclohexyl-benzylamine M.p. of the hydrochloride: 193 to 197°C.

Prepared from 2-amino-3-carboxy-benzyl bromide and N-ethyl-cyclohexylamine analogously to Example 25. - 181 - 40146 i Kxamplc A Syrup containing 4 mg of 2-amino-3-bromo-5-carbethoxy-N,N- diethyl -benzylamine hydrochloride per 10 ml Composition: 100 ml of syrup contain: Activc ingredient' 0.04 g tartaric acid 0.5 g benzoic acid 0.2 g ammonium chloride 0.4 g glycerine 10.0 g sorbitol 50.0 g red food colouring 0.01 g raspberry flavouring 4K24 0.25 g (Messrs. Bonke, Roberts & Co.) ethanol 10.0 g distilled water ad 100.0 ml Method of preparation: About 45 g of distilled water were heated to 80° and the tartaric acid, benzoic acid, active ingredient, food colouring and sorbitol were dissolved successively therein. The glycerine and a 20% solution of the ammonium chloride were subsequently added. After cooling to room temperature, Lhe eth.inol and the raspberry flavouring were stirred into - 182 - 40146 the mixture. The syrup was made up to the given volume nnd filtered in a suitable manner. 10 ml of syrup contain 4 mg of 2-amino-3-bromo-5-carbethoxy-N,N-diethyl-benzylamine 5 hydrochloride Example B Drop solution containing 4 mg o^ 2-amino-3-bromo-5-carbeth- oxy-N.N-diethyl-benzylamine hydrochloride per ml Composition: 10 100 ml of drop solution contain: Active ingredient 0, .4 ft methyl p-hydroxybenzoate 0. .07 g propyl p-hydroxybenzoate 0. .03 g polyvinylpyrrolidone 5. .0 g aniseed oil 0. .01 ft fennel oiI 0. © o ft ethanol 10. .0 8 distilled water ad o o .0 ml Method of preparation: The p-hydroxybenzoic acid esters, polyvinylpyrrolidone and active ingredient were dissolved successively in the water heated to 80°C. The solution was cooled and the mixture of the flavourings with ethanol was stirred in. The mixture was made up to the given volume with water and filtered - 183 - 40146 through a suitable filter. 1 ml of drop solution contains 4 mg of 2-amino-3-bromo-5-carbethoxy-N,N-diethy1-benzylamine hydrochloride. Example C Tablets containing 4 mg of 2-atnino-3-bromo-5-cnrbethoxy-N,N-diethyl-benzylamine hydrochloride Composition: I tablet contains: Aclivc ingredient lactosc potato starch po iyv inyIpyrro 1 idone magnesium stearate Method of preparation: The active ingredient was mixed with lactose nnd potato starch and was granulated through a screen of I mm mesh size with a 20% aqueous solution of the polyvinylpyrrolidone. The moist granulate was dried at &0"C, again passed through the said screen and mixed with magnesium stearate. The mixture was pressed into - 184 - 4.0 mg 60.0 mg £1.0 mg 4.0 mg 1.0 mg 110.0 mg 40146 tablets.

WeighI of tablet: 110 mg Punch: 7 inm Example D 5 Coated Tablets containing 4 mg of 2- araino-3-bromo-5-carbethoxy-N,N-diethy1-benzyInmine hydrochloride The tablets prepared according to Example C were covercd according to a known method with a coating 10 consisting essentially of sugar and talcum. The finished pills were polished with beeswax.

Weight of coated tablet: 200 mg Example F.

Suppositories containing A mg of 2-amino-1-bromo-*i-1 r> carbethoxy-N,N-diethy 1 -benzylamine hydrochloride Composition: I suppository contains: Active ingredient u.0 mg suppository mass (e.g.*Witepsol W 45) 1 696.0 mg 1 700.0 mg - 185 - N.B. *Witepsol is a Trade Mark 4 0 1 •! 6 Method of preparation: The finely pulverized substance was stirred into the molten suppository mass cooled to 40 C and homogenized. The mass was poured into slightly pre-cooled moulds at about ir)"C.

Ex.nmplc F Ampoules containing 4 mg of 2-amino-3-bromo-5-carbethoxy- N,N-dicthy1-benzylamine hydrochloride Compos iI ion: I ampoule contains: Active ingredient 6.0 mg tartaric acid 2.0 mg glucose mg distilled water ad 2.0 ml Method of preparation: The distilled water was heated to 80"C and tartaric acid and the active ingredient were dissolved therein whilst stirring. After cooling to room temperature, Lhe glucose was dissolved and the mixture was made up to the given volume. The solution was filtered sterile. - 186 - 4 014 6 Pilling: into white ampoules of 2 ml capacity. Sterilisation: 20 minutes at 120°C.

Example C Tablets containing 40 mg of 2-amino-3-bromo-5-carbethoxy-N,N-diethy1-benzylamine hydrochloride Composition: 1 tablet contains: Active ingredient lactose potato starch polyvinyI pyrrolidonc magnesium stearate Method of preparation: The active ingredient was admixed with lactose and potato starch and was granulated through a screen of 1 mm mesh size with a 20% aqueous solution of the polyvinylpyrrolidone. The moist granulate was dried at A0"C, again passed through the said screen and mixed with magnesium stearate. The mixture was pressed into tablets.

Weight of tablet: 110 mg Punch: 7 mm - 1H7 - 40.0 mg 34.0 mg 31.0 mg 4.0 mg 1.0 mg I10.0 mg

Claims (1)

1. 0140 C I AIMS Compounds of general formula (I) [.wherein Rj represents a hydrogen atom, an aliphatic acyl group or an optionally substituted aromatic acyl group; R2 represents a hydrogen, chlorine or bromine atom; R^ represents a fluorine atom; a methyl group in the 3-, 4- or 5-position of the phenyl nucleus; a methyl group in the 2- or 6-position of the phenyl nucleus when at least one of Rj and R2 is other than a hydrogen atom; a straight or branched chain alkyl group with 2 to 4 carbon atoms; a trif1uoromethyl , cyano, carbamoyl, carbalkoxy, acetyl or 1-hydroxyethyl group; a carboxyl group when at least one of Rj, R2, R4 and R^ is other than a hydrogen atom; an alkoxy group in the 3-, 4-or 5-position of the phenyl nucleus; an alkoxy group in the 2- or 6-position of the phenyl nucleus when R2 represents a chlorine or bromine atom, or a group of formula ,Rc / -ch2-n \ (wherein Rg and R^, which may be the same or different, each represents an alkyl, cycloalkyl or hydroxycycloalkyl group or Rg and R7 together with the nitrogen atom to which they are attached represent a pyrrolidine, piperidine or morpholine ring); and R^ and R^, which may be the same or different, each represents a hydrogen atom; a straight or branched chain alkyl group with 1 to 5 carbon atoms which may obtaionally be substituted by 1 or 2 hydroxy groups, an alkenyl group with 2 to 4 carbon 188 4 0116 atoas; a cycloalkyl group Mith 5 to 7 carbon atons which may optionally be substituted by 1 or 2 hydroxy groups; a benzyl group or a Morpholinocarbonylmethyl group; or and Rg together with the nitrogen aton to which they are attached represent a pyrrolidine, piperidine, hexamethyleneamine, morpholine, N-methyl-plperazlne or camphidine rl and acid addition salts thereof. Z. Compounds of general formula R2 represents a hydrogen, chlorine or bromine atom; R^ represents a fluorine atom; a methyl group in the 3-, 4- or 5-position of the phenyl nucleus; a methyl group in the 2- or 6-position of the phenyl nucleus when at least one of Rj and R2 is other than a hydrogen atom; a straight or branched chain alkyl group with 2 to 4 carbon atoms; a trifluoromethyl, cyano, carbamoyl, carbethoxy, acetyl or 1-hydroxyethyl group; a carboxy group, when at least one of Rj, R2, R^ and R^ is other than a hydrogen atom a methoxy group in the 3-, 4- or 5-position of the phenyl nucleus, a methoxy group in the 2- or 6-position of the phenyl nucleus when R2 represents a chlorine or bromine atom; or a group of formula -CN,-N 2 \o (wherein Rg and R^, which may be the same or different, each 189 4 0110 represents a methyl, cyclohexyl or hydroxy-cyc lohexy I group; or R(j ;ind R^ together with the nitrogen atom to which they are altached, represent a pyrrolidine, piperidine or morpholine ring); and and R,., which may be the same or different, each represents a methyl, ethyl, cyclohexyl or hydroxycyclo-hexyl group; or and R^, together with the nitrogen atom to which they are both attached, represent a pyrrolidine, piperidine, hexamethyleneamine, morpholine or N-methyI piperazine ring_7 and physiologically compatible acid addition salts thereof. J. 2-Ajni no- J-l»romo-r)-carl>ethoxy-N, N-dieLhy I-benzy lamine anti pliysiolni'.ica I ly compatible acid uddiLion salts thereof. U. N- l\l hy I - 2-am Lno- 3-1»romo- r>-ca rboxy-N-cyclohexy 1 -hen/.y I ami ne and physiologically compatible acid addition sal I.he reof. r). N-EthyI-2-amino-5-bromo-N-cyclohexy1-3-fluoro-benzylamin and physiologically compatible acid addition salts thereof. (>. N-( 2-Amino-5-bromo-3-inethy 1-benzy l)-hexame thy leneamine and physiologically compatible acid addition salts thereof. 7. N-(2-Amino-r>-bronio--4-lcrt. -buty 1-benzyl)-morphol ine antl physiologically conipaLihle acid addition salts thereof. •S. 2-Ami no- 3-bromo-N; N-d i methy 1-5-f luoro-benzy lamine and physiologically compatible acid addition salts thereof. - 100 - 40146 Compounds as claimed in claim 1 other than those claimed in claims 3 to 8 as herein specifically described. 10. Compounds of general formula (I) [wherein > Rj represents a hydrogen atom, an aliphatic acyl group or an optionally substituted aromatic acyl group; R2 represents a hydrogen, chlorine or bromine atom; R^ represents a fluorine atom; a methyl group in the 3-, 4- or 5-position of the phenyl nucleus; a methyl group 1n the 2-or 6-position of the phenyl nucleus where at least one of Rj and R2 lo is other than a hydrogen atom; a straight or branched chain alkyl group with 2 to 4 carbon atoms; a trifluoromethyl, cyano, carbamoyl, carbethoxy, acetyl or 1-hydroxyethyl group; a carboxyl group, when at least one of R2» R4 and r5 is other than a hydrogen atom; a methoxy group in the 3-, 4- or 5-position of the phenyl nucleus, a methoxy group in the 15 2- or 6-position of the phenyl nucleus when R2 represents a chlorine or bromine atom; or a group of formula /6 -cn2-n^ R7 (wherein Rg and R^, which may be the same or different, each represents an alkyl, cycloalkyl or hydroxycycloalkyl group); and and Rg, which may be the same or different, each represents a hydrogen atom; a straight or 20 branched chain alkyl group with 1 to 5 carbon atoms optionally substituted by a hydroxy group; an alkenyl group with 2 to 4 carbon atoms; a cycloalkyl group with 5 to 7 carbon atoms optionally substututed by a hydroxy group; 191 40141) a benzyl group or a morpholinocarbonylmethyl group; or R4 and Rj together with the nitrogen atom to which they are both attached represent a pyrrolidine, piperidine, hexanethyleneamine, morpholine, N-methyl-plperazlne or 5 camphidine ring] and physiologically compatible acid addition salts thereof. 11. Compounds of general formula 10 (D [^wherein Rj represents a hydrogen atom or an acetyl or butyryl group; R2 represents a hydrogen, chlorine or bromine atom; R^ represents a fluorine atom; a methyl grouD in the 3-, 4- or 5-position of the phenyl nucleus; a methyl group in the 2- or 6-position of the phenyl nucleus when at least one of Rj and R2 is other than a hydrogen atom; a trif1uoromethy1 group; a carbalkoxy group containing 15 from 1 to 3 carbon atoms in the alkoxy portion; a carboxyl group, when at least one of Rj, R2, R^ and Rg is other than a hydrogen atom; or a group of formula -CH?-N N 192 4 0 116 (wherein and each representee methyl group or and Ry together with the nitrogen atom to which they are attached represent a pyrrolidine, piperidine or morpholine ring); and 5 and R^, which may be the same or different, each represents a hydrogen atom; a methyl, ethyl, cyclohexyl, hydroxycyclohexyl or benzyl group; or a branched chain alkyl group with A carbon atoms optionally substituted by 1 or 2 hydroxy groups; or R^ and together with 10 the nitrogen atom to which they are both attached represent a pyrrolidine, piperidine, hexamethyleneamine or morpholine ring| and physiologically compatible acid addition salts thereof. l>. A process for the preparation of compounds of 15 general formula 1 as defined in claim 1 which comprises reacting a compound of formula (wherein and are as defined in claim 1, R^' represents the group -CJ^-X or is as defined in claim 1 for R^, and X represents a chlorine, bromine or iodine atom or a - 193 - 4 0 1 1 U hydroxy, ncyloxy, nutfonyloxy, alkoxy, nryloxy, nmlkoxy irialkylunutuuiuu or pyrillinium group) with a compound o formula ^R, II - N * (111) (wherein and R,. arc as defined in claim 1). 13. A process as claimed in claim 12 wherein the reacLion is effected in the presence of a solvent. 14. A process as cin lined In claim 12 or claim It wherein the reaction is effected at temperatures from -70 to 2«»°C. 15. A process as claimed in claim 12 or claim 13 wherein a compound of formula II as defined in claim 12 (wherein X represents a sulfonyloxy group) is reacted with a compound of formula III at temperatures from -70 to 50 °C. 1<>. A process as claimed in claim 12 or claim 13 wherein a compound of formula 11 as defined in claim 12 (wherein X represents a halogen atom) is reacted with a compound of formula 11 I at temperatures from 0 Lo 150°C in the presence of hydrogen halide binding agent. 17. A process as claimed in claim 12 or claim 13 wherein a compound of formula II as defined in claim 12 - 104 - 40146 (wherein X represents nn acyloxy, alkoxy, aryloxy or aralkoxy group) is reacted with a compound of formula 111 at temperatures from 0 to 200°C in the presence of an acid catalyst. 18. A process as claimed in claim 12 or claim 13 wherein a compound of formula II as defined in claim 12 (wherein X represents a hydroxyl group) is reacted with a compound of formula III at temperatures from 120 to 180°C in the presence of an acid or alkaline catalyst. 19. A process as claimed in claim 12 or claim 13 wherein a compound of formula II as defined in claim 12 (wherein X represents a trialkylammonium or pyridinium group) is reacted with a compound of formula 111 at temperatures from 120 to 180°C. 20. A process as claimed in claim 19 wherein the reaction is effected in the presence of an excess of the compound of formula III. 21. A process for the preparation of compounds of general formula I as defined in claim 10 which comprises reacting a compound of formula CH X R (II) 3 R 2 - 195 - 4 0 116 (wherein Rj and R^ ore as defined in claim 10, R^' represents the group -Cl^-X or is as defined in claim 10 £or R^ and X represents a chlorine, bromine or iodine atom) with a compound of formula II - N * (111) (wherein R^ and are as defined in claim 10). 22. A process for the preparation of compounds of general formula 1' as defined in claim 11 which comprises reacting a compound of formula (wherein Rj and R^ are as defined in claim 11, R^' represents the group -CH2"X or is as defined in claim 11 for R^ and X represents a chlorine, bromine or iodine atom) with a compound of formula II - 4 (111) ^K-> (wherein and R,. are as defined in claim 11). 23. A process for the preparation of compounds of general formula 1 | wherein Rj, R2, and Rj are as - I ')(> - 401 40 defined 1n claim 1 and R-j represents a fluorine atom; a methyl group in the 3-, 4- or 5-posltlon of the phenyl nucleus; a methyl group in the 2- or 6-pos1t1on of the phenyl nucleus when at least one of Rj and R2 Is other than a hydrogen atom; a straight or branched chain alkyl group with 2 to 4 carbon atoms: a trifluoromethyl, cyano, carbamoyl, carbalkoxy, acetyl or 1-hydroxyethyl group; a carboxyl group when at least one of Rj, R2, R4 and R& is other than a hydrogen atom; a methoxy group in the 3-, 4- or 5-position of the phenyl nucleus; a methoxy group in the 2- or 6-position of the phenyl nucleus when R2 represents a chlorine or bromine atom; or a group of formula /4 — CHo-N (wherein Rg and R^ are as defined in claim 1) which comprises reacting a compound of formula Ho-X (II) V (wherein Rj, R^ and R^ are as hereinbefore defined and X represents a hydroxyl, acyloxy, sulfonyloxy, alkoxy, aryloxy, aralkoxy, trialkylammonium or pyridinium group) with a compound of formula /R4 H-N^ (III) R5 (wherein R^ and R^ are as hereinbefore defined). 24. A process for the preparation of compounds of general formula 1 (wherein Rj, R3> Rg and R7 are as 197 4 0116 il(<rinc<l in claim 1, R^ represents a chlorine or bromine atom, and R^ and R^ arc as defined in claim 1 with the proviso that they do not represent alkenyl groups)which comprises halogenating a compound of formula (IV) (wherein R. and R^ are as defined in claim 1 and R,' and 1 i 4 R ' are as defined in claim 1 for R. and Rr with the 5 4 5 proviso that they do not represent alkenyl groups). 25. A process as claimed in claim 24 wherein the reaction is effected in the presence of a solvent. 20. A process as claimed in claim 24 or claim 25 wherein the halogenalion is effected by means of chlorine, bromine, tribromophenyl hypobromite or iodosobenzene dichloride. 27. A process as claimed in claim 20 wherein one mole of the halogenating agent or a slight excess thereof is used. 28. A process as claimed in any of claims 24 to 27 wherein Lhe halogenation is effected at temperatures - l')8 - 401 4G of from -20 to 50°C. 29. A process for the preparation1of compounds of general formula I (wherein , R^, Rfo and are as defined in claim 10, R^ represents a chlorine or bromine atom, and R, ami R, are as defined in claim 4 5 10 with the proviso that they do not represent alkenyl groups) which comprises halogenating a compound of formula IV (wherein R. and R0 are as defined in claim 10 and R.' i j a 10 and R ' are as defined in claim 10 for R, and Rc with the proviso that they do not represent alkenyl groups). 30. A process for the preparation of compounds of general formula I' (wherein R,, R_, R., Rc, R, and R, I j U j b / are as defined in claim 11 and R2 represents a chlorine 15 or bromine atom) which comDrises halogenating a compound of formula / R4 CH -N 2 (wherein R^, R^, R^ and R^ are as defined in claim 11). - 199 - 4 0 116 31. A proccss for the preparation of compounds of general formula 1 as defined in claim 1 with the proviso that R^ and/or R^ represent hydrogen atoms which comprises removing one or two protecting groups from a compound of formula (whorein R^, R^ and R,. are as defined in claim I, Yj represents n hydrolyt ic.nl ly or hydrogenolytical ly removable protecting group for an amino group or is as defined in claim 1 for R^ and Y^ represents a 10 hydrolytically or hydrogenolytically removable pro tecting group for an amino group or is as defined in claim 1 for R^, with the proviso that at least one of Yj and represents n protecting group). 32. A process as claimed in claim 31 wherein the 15 reaction is effected in the presence of a solvent. 33. A process as claimed in claim 31 or claim 32 wherein a compound of formula V (wherein Y^ and/or Y2 represent acyl, trimethylsilyl or tetrahydropyranyl-(2) groups) is used as starting material, and these - 200 - 40146 groups are split off hydrolytically at temperatures from 20 to 150°C. 34. A process as claimed in claim 31 or claim 32 wherein a compound of formula V (wherein and/or Y^ represent benzyloxycarbonyl or benzyl groups) is used as starting material and these groups are split off hydrogenolytically at room temperature. 35. A process for the preparation of compounds of general formula I as defined in claim 10 with the proviso that Rj and/or R^ represent hydrogen atoms which comprises removing one or two protecting groups from a compound of formula (wherein R2, R^ and R^ are as defined in claim 10, Y^ represents hydrolytically or hydrogenolytically removable protecting group for an amino group or is as defined in claim J() for R^ and Y2 represents a hydrolytically or hydrogenolytically removable protecting group for an amino group or is as defined in claim 10 for R,. with 4 the proviso that at least one of Y^ and Y2 represents a protecting group). 1 (v) 201 4 0 116 36. A process for the preparation of compounds of general formula I* as defined in claim 11 with the proviso that R^ and/or R^ represent hydrogen atoms which comprises removing one or two protecting groups from a compound of formula (V') (wherein R^, R^ and R^ arc as defined in claim 1, Yj represents a hydrolytically or hydrogenolytically removable protecting group for an amino group or is as defined in claim 11 for R^ and represents ;» 10 hydrolytically or hydrogenolytically removable pro tecting group for an amino group or is as defined in claim 11 for R^, with the proviso that at least one of Yt and Y^ represents a protecting group). 37. A process for the preparation of compounds of 15 general formula 1 (wherein Rj, R2, and R$ are as defined in claim 1 and R^ represents a 1-hydroxymethyl group) which comprises reducing a compound of formula (VI) 202 - 40146 lo (wherein R^, R^, R^ and R^ are as defined in claim 1). IK. A process as claimed in claim 37 wherein the reaction is effected in the presence of a solvent. 19. A process as claimed in claim 37 or claim 38 wherein the reduction is effected by means of a compicx metal hydride, or aluminium alcoholate in the presence of a primary or seconary alcohol or hydrogen in the presence of a catalyst. AO. A process as claimed in any of claims 37 to 39 whcroin the reduction is effected al temperatures from -20°C up to the boiling point of the solvent used. 41. A process for the preparation of compounds of general formula I (wherein R^, R2, R^ and R,. are as defined in claim ID and R^ represents a 1-hydroxyethyl group) which comprises reducing a compound of formula (VI) 15 (wherein R^, R2, R^ and R,. are as defined in claim 10). 42. A process for the preparation of compounds of general formula I (wherein R^, R2> R^ and R^ are as defined in claim 1, at least one of Rj, R£, and being other than a hydrogen atom, and represents a carboxyl group) - 203 - 4 0 111* .which comprises hydrolysing a compound of formula R (VI I) R 2 A R 1 lu (wherein Rj, R2, Rj and R^ are as defined 1n claim 1, at least one of Rj, k2, r4 and R«> being other than a hydrogen atom and A represents a functional derivative of a carboxyl group). 43. A process as claimed in claim 42 wherein the reaction Is effected In the presence of a solvent. 44. A process as claimcd in claim 42 or claim 41 wherein the reaction is effected in the prescncc of an acid or a base. 4*>. A process as claimed in any of claims 42 to 44 wherein the reaction is effected at temperatures from r»0 to I *>()' ('.. 4(>. A process for the preparation of compounds of general formula 1 (wherein R^ represents a hydrogen atom, R^ represents a carboxyl group and R2» R^ and R^ are as defined in claim 10, at least one of R2, R4 and R5 being other than a hydrogen atom) which comprises hydrolysing a compound of formula (Vll) 204 40146 (wherein Rj, R2, R^ and Rj are as defined in claim 10, at least one of R2, R4 and R5 being other than a hydrogen atom, and A represents a cyano, carbethoxy or carbamoyl group). 47. A process for the preparation of compounds of general formula 1* 5 (wherein Rj represents a hydrogen atom, Rj represents a carboxyl group and R2, R^ and Rg are as defined In claim 11, at least one of R2, and Rj being other than a hydrogen atom) which comprises hydrolysing a compound of formula (Vll*) 10 15 (wherein Rj, R2, R^ and Rg are as defined in claim 11, at least one of R2, R^ and R^ being other than a hydrogen atom, and A represents a cyano, carbalkoxy or carbamoyl group). 48. A process for the preparation of compounds of general formula I (wherein Rj, R2, R4 and Rg are as defined in claim 23, at least one of Rj. R2> R4 and being other than a hydrogen atom, and R^ represents a carboxyl group) which comprises hydrolysing a compound of formula /R4 (VII) (wherein Rj, R2, R4 and R^ are as defined in claim 23, at least one of R^, R2, R4 and Rg being other than a hydrogen atom, and A represents a functional derivative of a carboxyl group). 20'j 4 014 6 49. A process for the preparation of compounds of general formula I (wherein represents a hydrogen atom, is as defined in claim 1, R^ is as defined in claim 1 with the proviso that it cannot represent a cyano, carboxyl, carbalkoxy, carbamoyl or acetyl group, and R^ and R^ are as defined in claim 1 with the proviso that neither of and R^ represent a morpholinocarbonylmethyl group) which comprises reducing a compound of formula - R4 CO-N * ^R5 (VI Ii) 2 (wherein is as defined in claim 1, R^ is as defined in claim 1 with the proviso that it cannot represent a cyano, carboxyl, carbamoyl, carbalkoxy or acetyl group, ond R^ and R,. are as defined in claim 1 with the proviso that neither of R^ and R,. represent a morpho1i noca rbonylme thy1 group). *50. A process as claimed in claim 49 wherein the reaction is effected in the presence of a solvent. 51. A process as claimed in claim 49 or claim j0 wherein the reduction is effected by means of nnsccnt - ZOb - 4U14U 10 hydrogen, catalytically activated hydrogen or a complex metal hydride. 52. A process as claimed in any of claims 49 to 51 wherein the reaction is effected at temperatures from 30 to 70°C. 53. A process as claimed in any of claims 49 to 51 wherein the reaction is effected at the boiling temperature of the solvent used. 54. A process for the preparation of compounds of general formula I (wherein represents a hydrogen atom, 1*2 is as defined Ln claim 10, R^ is as defined in claim 10 with the proviso that it cannot represent a cyano, carboxyl, carbethoxy or acetyl group, and and R^ are as defined in claim 10 with the proviso that neither of and R^ represents a morpholinocarbonylmethyl group) which comprises reducing a compound of formula ^ R, '► (VII) Nil 2 (wherein R2 is as defined in claim 10, R^ is as defined in claim 10 with the proviso that it cannot represent a cyano, 20 carboxyl, carbethoxy or acetyl group, and R^ and R,. are - 207 - 15 40 146 CO-N^ U as defined in claim 10 with the proviso that neither of R^ and R,. represents a morpholinocarbonylmethyl group). *35. A process for the preparation of compounds of general formula 1* (wherein represents a hydrogen atom, R^, R^ and R^ are as defined in claim 11 and R^ is as defined in claim 11 with the proviso that It cannot represent a carboxyl or carbalkoxy group) which comprises reducing a compound of formula •R< R5 (VIII') 10 (wherein R^, R2» R^ and R,. are as defined in claim 11 with the proviso that R^ cannot represent a carboxyl or carbalkoxy group). ">b. A process for the preparation of compounds of general formula 1 (wherein R^ represents a hydrogen l!» atom and R„, R_, R, and R,. are as defined in claim 1) 2 > 4 j which comprises reducing a compound of formula (IX) - 208 - 40146 (wherein R^, R^, R^ ami are as defined in claim 1). 57. A process as claimed in claim 56 wherein the reaction is effected in the presence of a solvent. 58. A process as claimed in claim 56 or claim 57 ^ wherein the reaction is effected by means of nascent hydrogen, hydrogen in Lhe presence of a catalyst, a complex metal hydride or tin (II) chloride and hydrochloric acid. 59. A process as claimed in any of claims 56 to 58 lO wherein the reduction Ls effected at temperatures from O to 100°C. 60. A process for the preparation of compounds of general formula 1 (wherein R^ represents a hydrogen .itom and R2> R-jt R^ and R,. are as defined in claim 23) IB which comprises reducing a compound of formula (IX) (wherein R^, R^, R^ and R,. are as defined in claim 23). 61. A process for the preparation of compounds of general formula I (as defined in claim 1 with Lhe proviso that Rr does not represent a group substituted by one or - 209 - two hydroxyl groups or a hydrogen atom) which comprises reacting a compound of formula H R 3 4 (X) R 1 (wherein R, , R_, R, and R. are as defined in claim 1) 12 3 4 with a compound of formula (wherein R,." is as defined in claim 1 for R^ with the exception of a hydrogen atom and a group substituted by one or two hydroxyl groups, and W represents n halogen atom or a sulfonic group). (>2. A process as claimed in claim 61 wherein the reaction is effected in the presence of a solvent. 63. A process as claimed in claim 61 or claim <>2 wherein Lhe reaction is effected at temperatures from -20 to l*iOwC. <»4. A process for the preparation of compounds of general formula 1 (as defined in claim 1 with the proviso that R,. does not represent a group substituted by one or two hydroxyl groups or a hydrogen atom) which comprises reacting a compound of formula 210 40146 10 I (wherein R^, R^, R^ and R^are as defined in claim 23) with a compound of formula R5m W (wherein R^" is as defined in claim 23 for with the exception of a hydrogen atom and a group substituted by one or two hydroxyl groups, and W represents a halogen atom or a sulfonic acid group). 65. A process for the preparation of compounds of general formula I (wherein R^, R2, R^ and R^ are as defined in claim 1 and represents a methyl group) which comprises reacting a compound of formula ,H (X) (wherein Rj, R^, and R^ are as defined in claim 1) with formaldehyde in the presence of formic acid, bb. A process for the preparation of compounds of - 211 - 4 0 1 J 6 general formula I (wherein R^, R2. R-j and R^ arc as defined in claim 23 and R,. represents a methyl group) which comprises reacting a compound of formula .H (wherein R^, R^, R^ and R^ are as defined in claim 23) with formaldehyde in the presence of formic acid. <>7. A process for the preparation of compounds of general formula I (as defined in claim 1 with the proviso that K.j docs not represent an acetyl group) which comprises reacting a compound of formula (XII) (wherein R( and R2 are as defined in claim 1 and R^" is .is defined in claim 1 for R.^ with the proviso thai it <loes nol represent an acetyl group) with a compound of formula II N * (III) ^R5 (wherein and R are as defined in claim 1) or with - 212 - 40146 the corresponding fonnamide in the presence of formic acid and if necessary subsequently heating the product with a dilute acid. 68. A process as claimed in claim 67 wherein the > reaction is effected in the presence of a solvent. 69. A process as claimed in claim 67 or claim 68 wherein the reaction is effected at temperatures from 50 to 250°C. 70. A process for the preparation of compounds of 10 general formula 1 (as defined in claim 23 with the proviso that does not represent an acetyl group) which comprises reacting a compound of formula (wherein R^ and R^ are as defined in claim 23 and R^" is as defined in claim 1 for R^ with the proviso that 15 it does not represent an acetyl group) with a compound of formula ^R, h—n— (iii) ^R5 (wherein R^ and R^ are as defined in claim 23) or with 211 40146 lo the corresponding fortnamide in the presence of formic acid and if necessary subsequently heating the product with a dilute acid. 71. A process for the preparation of compounds of general formula I (wherein represents a hydrogen atom, Rj is as defined in claim 1 with the exception of the acetyl group, and R^, Rj and R^ are as defined in claim 1) which comprises reducing a compound of (Xlll) (Xllla) ll (wherein Rj, R^ and R,. are as defined in claim 1, K^" is as defined in claim 1 for R^ with the proviso that it does not represent an acetyl group, and Z represents a cyclohexylidene group optionally substituted by one •5 or two hydroxy groups, an alkylidene group with 3 to (> carbon atoms or a morpholinocarbonylmethylidene group). 72. A process as claimed in claim 71 wherein the - 214 - 4 014 6 reduction is effected in the presence of a solvent. 73. A process as claimed in claim 71 or claim 72 wherein the reduction is effected by means of catalytically activated hydrogen, nascent hydrogen or a complex metal hydride. 74. A process as claimed in any of claims 71 to 73 wherein the reduction is effected at temperatures from -r»0 to 100 °C. 7*>. A process for the preparation of compounds of general formula I (wherein R^ represents a hydrogen atom, R.j is as defined in claim 23 with the exception of the acetyl group, and R^, R^ and R,. are as defined in claim 23) which comprises reducing a compound of formula -^5 (whcrc-in Rj, R^ and R are as defined in claim 71. R^" is as defined in claim 23 for R^ with the proviso (XllI) or a compound of formula (XI I la) 40146 that il (Iocs not represent an acetyl group, and '/. represents a cyclohexylidene group optionally substituted by one or two hydroxy groups, an alkylidene group with 3 to 5 carbon atoms or a morpholinocarbonylO inclhyl itlenc group). /(>. A process for the preparation of compounds of general formula I as defined in claim 1 with the proviso that R^ docs not represent a 1-hydroxymethyl group which comprises reacting a compound of formula <:ii2oii (xiv) lo (wherein R( nnd arc- ;»s defined in claim I nnd R^'** is as defined in claim I for R^ with the proviso that il does not represent the 1-hydroxyethyl group) wiLh a compound of formula (xv) (wherein R^''' represents a hydrogen atom or an nlkyl 15 group with 1 to 3 carbon atoms, and R^''* represents an alkyi group with 1 to 3 carbon atoms or a cyclohexyl - 2l(> - 40146 group, or R^'' * and R,.'" together with the nitrogen atom to which they are attached, represent a morpholino or piperidino group) or with a compound of formula (wherein R. ana R_ arc as defined in claim 1 and R„ 4 5 8 77. A process as claimed in claim 76 wherein the reaction is effected in the presence of a solvent. 78. A process as claimed in claim 76 or claim 77 wherein the reaction is effected at temperatures from 70. A process as claiincd in claim 76 or claim 77 wherein Lhe reaction is effected at temperatures from 120 to 1 x<>"C.. sO. A process for tlu- preparation of compounds of general formula I as defined in claim 23 with the proviso that does not represent a 1-hydroxyethyl group which comprises reacting a compound of formula (XVa) 5 represents an alkyl, aryl or aralkyl group). 10 100 to 250*'C. 1 XIV - 217 - 40146 (wherein Rj and arc as defined in claim 23 ond R^''' is as defined in claim 23 for R^ with the proviso that il docs not represent the 1-hydroxyethyl group) with a compound of formula (wherein R^"" represents a methyl or ethyl Kroup and Rr *" represents a mcLhyl, ethyl or cyclohexyl group, or R^"' *ind R,.'" together with the nitrogen atom to which lhey arc attached represent n morpholino group) or with a compound of formula i win-re in R. and Rt. ;ir«- defined in claim 7'1 and K., /» » s npresents an alkyl, aryl or arnlkyl >;ronp). s|. A process for Lhe preparation of compounds of general formula I* (wherein R. , R„, R..,, R, and Rr arc 1 lih > as dcfincil in claim 1) which comprises reacting a compound of formula XV r XVa (XVI) (wherein R^ and R.^ are as defined in claim 1 and K() - IIK - 40146 represents a hydrogen atom or an alkyl, aryl, aralkyl or hydroxy group) with a compound of formula (wherein and are as defined in claim 1) and if necessary subsequently hydrolysing the product formed. 82. A process as claimed in claim 81 wherein the reaction is effected in the presence of a solvent. 83. A process as claimed in claim 81 or claim 82 wherein the reaction is effected at temperatures from 100 to 200"C. 84. A process as claimed in claim 81 or claim 82 wherein the reaction is effected at temperatures from l .'O to 18()"C. sr>. A process as claimed in any of claims 81 Lo 84 wherein Lhe optional subsequent hydrolysis is effected in the presence of an acid or base. 8(>. A process as claimed in claim 85 wherein the optional subsequent hydrolysis is effected at temperatures up to the boiling point of the solvent 87. A process for the preparation of compounds of general formula I' (wherein R^, R2, R-j, R^ and R,. are II 5 (III) used. - 210 - 4 0 14 6 as dcfini'd in claim 23) which comprises reacting a compound of formula cll. ] (wherein R2 and R3 are as defined in claim 23 and Rg represents an alkyl, aryl, aralkyl or hydroxy group) with a compound of formula •4 II N (ill) R5 (wherein and R,. are as defined in claim 23) and if necessary subsequently hydrolysing Lhe product formed. xh . A process for the preparation of compounds of Koneral formula 1 (wherein Rj, R2, R^ and R5 are as defined in claim 1 and R^ represents a carbalkoxy Kroup) which comprises reacting a compound of formula (wherein R^ R^ and R,. are as defined in claim 1 and It represents a carboxyl group or a functional derivative thereof) with a compound of formula r10 c (xvu1) - 220 - 4 01 -lu (wherein RjQ represents an alkyl group containing*from 1 to 4 carbon atons and C represents a hydroxyl group or a halogen atom). 89. A process as claimed in claim 88 wherein the reaction is effected in the presence of a solvent. 90. A process as claimed in claim 88 or claim 89 wherein the reaction is effected at temperatures from 0 to 100"C. *)1. A process as claimed in claim 88 or claim 8() wherein the reaction is effected at the boiling temperature of the solvent used. <)2. A process for the preparation of compounds of general formula I (wherein R^, R2, R^, and R^ are as defined in claim 23 and R^ represents a carbalkoxy r.roup) which comprises reacting a compound of formula R i XVI I (wherein R^, R2> R^ ami R^ are as defined in claim 23 and B represents a carboxyl group or a functional derivative thereof) with a compound of formula D XVIII io C (wherein Rjq represents an alkyl group containing from 1 to 4 carbon atoms 221 and C represents a hydroxy! group or a halogen atom. 03. A process for the preparation of compounds of general formula I as defined in claim 1 (wherein represents a carbamoyl group) which comprises partially hydrolysing the corresponding compound of formula I (wherein represents a cyano group). 04. A process for the preparation of compounds of Kenernl formula I (wherein Rj represents an aliphatic or optionally substituted aromatic acyl group and R^, Rj, R^ and R^ are as defined in claim 1 with the proviso that they do not represent groups containing reactive hydrogen atoms) which comprises acylating the corresponding compound of formula I (wherein Rj represents a hydrogen atom) with an appropriate acylating agent. 0*>. A process for the preparation of acid addition salts of compounds of general formula 1 as defined in claim 1 which comprises treating a compound of formula I with an appropriate acid. 9b. A process as claimcd in claim 0r> wherein the ucid is a physiologically compatible acid. 07. A process as claimed in any of claims 93 to Ob wherein the starting material is a compound of formula I - 222 - 40146 .-is defined in claim 10. 98. A process as claimed in any of claims 93 Lo 9b wherein the. starting material is a compound of formula I as defined in claim 11. 5 99. A process as claimed in any of claims 93 to 9b wherein the starting material is a compound of formula 1 as defined in claim 23. 100. A process for the preparation of compounds as claimed in claim 1 substantially as herein described. 10 101. A process for the preparation of compounds of general formula I as defined in claim 1 and acid addition salts thereof substantially as herein described with reference to Kxamples 1 to 379. I'1,?. A process for the preparation of compounds of 15 general formula I as defined in claim 10 and acid addition salts thereof substantially as herein described with reference to Kxamples 1 to 198 and 201to26ff. - 223 - 40146 103. A process for the preparation of compounds of general formula I* as defined in claim 11 and acid addition salts thereof substantially as herein described with reference to Kxamples 269 to 293 and 296 to 326. 104. A process for the preparation of compounds of general formula I as defined in claim 23 and acid addition snlts tliereof substantially as herein described with reference to Examples 328 to 358 and 378. 10:>. Compounds of general formula I as defined in claim 1 and acid addition salts thereof whenever prepared by a process as claimed in any of clciims 12 to 104. 106. Compounds of general formula 1 as defined in claim 10 and ncid addition salts thereof whenever prepared by n process as claimed in any of claims 21, 29, 3\ 41, 46, 54, 97 and 102. 107. Compounds of general formula T' as defined in claim 11 and acid addition sails thereof whenever prepared l»y a process as claimed in any of claims 22, 30, 36, 47, Vj, 98 and 103. 108 Compounds of general formula 1 as defined in - 224 - 40146 claim 24 nnd acid addition salts thereof whenever prepared by n process as claimed in any of claims 23, 4K, 60, 64, 66, 70, 7l>, 80, 87, 92, 99 nnd 104. 109. Pharmaceutic;!I compositions comprising as active ingredient at least one compound of formula I as defined Ln claim 1 or a physiologically compatible acid addition salt thereof in association with a pharmaceutical carrier or excipient. 110. Compositions as claimed in claim 109 in a form suitable for oral, rectal or parenteral administration. 111. Compositions as claimed in claim 110 in the form of syrups, drop solutions, tablets, coated tablets, capsules, powders, ampoules or suppositories. 112. Compositions as claimed in any of claims 109 to 111 in the form of dosage-units. 113. Compositions as claimed in claim 112 wherein . each dosage unit contains from 1 to 100 mg of active ingredient. 114. Compositions as claimed in claim 112 wherein each dosage unit contains from 4 to 60 mg of active ingredient. 115. Compositions as claimed in claim 112 wherein each dosage unit contains from 1 to 20 mg of active 40146 ingredient having a sccretolytic activity. 116. Compositions as claimed in claim 112 wherein each dosage unit contains from 4 to 15 mg of active ingredient having a secretolytic activity. S 117. Compositions as claimed in claim 112 wherein cnch dosage unit contains from 20 to 100 mg of active ingredient having an anti-ulcus activity. 11K. Compositions as claimed in claim 112 wherein each dosage unit contains from JO to 60 mg of active 1Q ingredient having an anti-ulcus activity. 119. Compositions as claimed in claim 109 wherein Lhe active ingredient comprises at least one compound of formula I as defined in claim 10 or a |>hy s i <> I !>>■, i t :i I I y compat il>Ie acid addition salt tliereof. 15 120. Compositions as claimed in claim 10') wherein the active ingredient comprises at least one compound of formula l' as defined in claim 11 or a physiologically compatible acid addition salt thereof. 121. Compositions as claimed in claim 109 wherein 20 the active ingredient comprises at least one compound of formula I as defined in claim 23 or a physiologically compatible acid addition salt thereof. 122. Composilions as claimed in any of claims 109 - 226 - 40146 to 121 containing a further active ingredient. 123. Pharmaceutical compositions substantially as herein described. 124. Pharmaceutical compositionis substantially as herein described with reference to Examples A to G. Dated this 11th day of April 1974. (signed) TOMKINS & CO., Applicants' Agents, 5 Dartmouth RoadT DUBLIN 6. - 227 -