FR2659334A1 - N-phenylglycinamide derivatives, their preparation and medicinal products containing them - Google Patents

Abstract

Compounds of formula: in which - R1 represents a hydrogen atom, an alkyl, alkoxycarbonyl or optionally substituted phenyl radical - R2 represents an alkoxy radical, an optionally substituted cycloalkyloxy radical, a cycloalkylalkyloxy, phenylalkyloxy, polyfluoroalkyloxy or cinnamyloxy radical, a chain -NR5R6 in which R5 and R6, which are identical or different, represent a hydrogen atom, an alkyl or optionally substituted phenyl radical, an indanyl, cycloalkylalkyl, cycloalkyl, or phenylalkyl radical, or alternatively R5 and R6 form, together with the nitrogen atom to which they are attached, a heterocycle, - R3 represents a phenylamino radical whose phenyl nucleus is optionally substituted, an optionally substituted phenyl radical, a naphthyl, indolyl or quinolyl radical, - R4 represents a substituted phenyl radical, their preparation and medicinal products containing them.

Description

leur préparation et les médicamets les contenant.M the present invention relates to N-phenyl glycinamide derivatives of formula

their preparation and the medicamets containing them.

 In formula (I), - R1 represents a hydrogen atane, an alkyl, alkoxycarbonyl or phenyl radical optionally substituted by one or more substituents chosen from halogen atanes and the alkyl, alkoxy, alkylthio, nitro and amino radicals, R2 represents an alkoxy radical, oycloalkyloxy (optionally substituted with at least one alkyl radical), cycloalkylalkyloxy, phenylalkyloxy, polyfluoroalkyloxy, cinnamyloxy, a chain -NR5R6 in which R5 and R6 identical or different represent a hydrogen atane, an alkyl radical, phenyl (optionally substituted by one or more substituents chosen from halogen atoms and alkyl, alkoxy, alkylthio radicals), indanyl, cycloalkylalkyl, cycloalkyl, phenylalkyl or else R5 and R6 form together with the nitrogen atom to which they are attached a heterocycle, - R3 represents a phenylamino radical (the phenyl nucleus of which is optionally substituted by one or more substituents ants chosen from halogen atoms and alkyl, alkoxy and alkylthio radicals), phenyl (optionally substituted by one or more substituents chosen from halogen atanes and alkyl, alkoxy and alkylthio radicals), naphthyl, indolyl or quinolyl, - R4 represents a phenyl radical substituted by one or more substituents chosen from halogen atoms, alkyl, alkoxy, dialkylamino, nitro, alkylthio, alkoxycarbonyl, acylamino, trifluoromethyl, methylenedioxy, trifluoromethoxy, trifluoromethylthio, phenoxy, phenyl or benzyl radicals.

 In the above definitions and those which will be cited below, unless otherwise stated, the alkyl and alkoxy radicals and the alkyl, alkoxy and acyl portions contain 1 to 4 carbon atoms in straight or branched chain and the cycloalkyl radicals and portials contain 3 to 6 carbon atanes.

 In formula (I), the halogen atoms are preferably chlorine, slab and fluorine atanes.

 When R5 and R6 form together with the nitrogen atane to which they are attached a heterocycle this is preferably a piperidiro ring optionally substituted by at least one alkyl radical, a perhydroazepinyl-1, indolinyl, tetrahydro-1,2 ring , 3,6 pyridyl-1, tetrahydro-1,2,3,4 quinolyl-1, pyrrolidinyl, 4H 2,3-dihydro-1,4-benzoxazine, 4H 2,3-dihydro-1,4-benzothiazine or N-alkyl tetrahydro-1,2,3,4 quinoxalinyl-1.

 The compounds of formula (I) containing one or more asymmetric centers have isaneric forms. The racemates and the enantiomers of these compounds also form part of the invention.

dans laquelle R1, R2 et R4 ont les mêmes significations que dans la formule (I).The compounds of formula (I) for which R3 represents a phenylamino radical in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atanes and the alkyl, alkoxy and alkylthio radicals can be obtained by actian of an isocyanate of formula
-R7 (II) in which R7 represents a phenyl radical optionally substituted by one or more substituents chosen from halogen atanes and alkyl, alkoxy and alkylthio radicals on an amino derivative of formula

in which R1, R2 and R4 have the same meanings as in formula (I).

 This reaction is generally carried out in an inert solvent such as tetrahydrofuran, dimethylformamide, a chlorinated solvent (chloroform, 1,2-dichloroethane for example), an aromatic solvent (benzene, toluene for example), at a temperature between 100C and the boiling point of the solvent.

 Ms isocyanates of formula (II) can be obtained by application or adaptation of the method described by R. RICHTER et al., The Chemistry of Cyanate and their thio derivatives, S.

PATAI, part 2, Wiley Nw YORK (1977).

dans laquelle R1, R2 et R4 ont les mêmes significations que dans la formule (I).Ms derivatives of formula (III) can be obtained by application or adaptation of the method described by T. WIELAND et al., Justus Liebigs Ann. Chem., 613, 84 (1958) or by adaptation of the method of GABRIEL (GIBSON et al., Angew Chem. Int. Ed., 7, 919 (1968) which consists in reacting a hydrazine of formula
H2N-NH R8 (IV) in which R8 represents a hydrogen atane or a methyl radical, on a derivative of formula

in which R1, R2 and R4 have the same meanings as in formula (I).

 This reaction is preferably carried out in an inert solvent such as an alcohol (methanol, ethanol for example) or a chlorinated solvent (dichloranethane, chloroform for example), at a temperature between 20 C and the temperature of boiling of the solvent.

The derivatives of formula (V) can be obtained by the action of an amine of formula
R4-NH-CH (R1) -CO-R2 (VI) in which R1, R2 and R4 have the same meanings as in formula (I), on a chloride of formula

 This reaction is generally carried out in an inert solvent (chloroform, 1,2-dichloro, 2 ethane for example), in the presence of a base such as a tertiary amine such as a trialkylamine, a carbonate or an alkali metal bicarbonate. , at a temperature close to 200C.

 The chloride of formula (VII) can be prepared by applying the method described by W. GRASSMANN et al., Ber., 83, 244 (1950).

The amines of formula (v ') can be obtained by the action of an amino derivative of formula R4-NH2 (VIII) in which R4 has the same meanings as in formula (I) on a brominated derivative of formula
Br-CH (R1) -CO-R2 (IX) in which R1 and R2 have the same meanings as in formula (I).

 This reaction is generally carried out in an inert solvent such as acetonitrile, dimethylformamide, tetrahydrofuran or a chlorinated solvent, optionally in the presence of a base such as an alkali metal hydride or an alkali metal bicarbonate , at the boiling point of the solvent.

The substituted anilines of formula (VIII) can be obtained by application w adaptation of the method described by
R. SCHRÖTER, Methoden der Otganischen Chemie, Houben Weil, Band
XI / 1, p. 360.

The brominated derivatives of formula (IX) can be obtained by branation of a derivative of formula
HCH (R1) -CO-R2 (X) in which R1 and R2 have the same meanings as in formula (I).

 This reaction is generally carried out by means of brane, optionally in the presence of acetamide.

Ms derivatives of formula (X) for which R2 represents an alkoxy, cycloalkyloxy optionally substituted radical, cycloalkylacoxy, phenylalkyloxy, polyfluoroalkyloxy or cinnamyloxy can be obtained by esterification of an acid of formula
HCH (R1) -COOH (XI) in which R1 has the same meanings as in formula (I).

 This esterification is carried out by any method known to a person skilled in the art for passing from an acid to an ester. One can for example react the corresponding alcohol in the presence of an acid such as sulfuric acid.

 The acids of formula (XI) for which R1 represents an alkoxycarbonyl radical can be obtained by application or adaptation of the dicrite method in Acta. Chem. Scand., B29, 687 (1975).

 Ms derivatives of formula (X) for which R2 represents a chain -NR5R6 can be obtained by the action of an acid of formula (XI) or a reactive derivative of this acid, on an amine HNR5R6 (XII) in which R5 and R6 have the same meanings as in formula (I).

 When the acid is used, the operation is carried out in the presence of a peptide condensing agent such as a carbodiimide (for example dicyclohexylcarbodiimide or N, N'-diimidazole carbonyl), in an inert solvent such as an ether (tetrahydrofuran, dioxane for example), an amide (dimethylformamide) or a chlorinated solvent (methylene chloride, 1,2-dichloroethane, chloroform for example) at a temperature between OOC and the reflux temperature of the reaction mixture.

 when a reactive acid derivative is used, it is possible to react the anhydride, a mixed anhydride or an acid halide or an ester (which can be chosen from the activated or inactive esters of l 'acid).

 The operation is then carried out either in an organic medium, optionally in the presence of an acid acceptor such as a nitrogenous organic base (trialkylamine, pyridine, diaza-1,8 bicyclo [5.4.0] undecene-7 or diaza-1,5 bicyclo [4.3.0] nonene-5 for example), in a solvent as mentioned above, w a mixture of these solvents, at a temperature between 0 C and the reflux temperature of the reaction mixture, ie in a two-phase hydroorganic medium in the presence an alkaline or alkaline earth base (soda, potash) or a carbonate or bicarbonate of an alkali or alkaline earth metal at a temperature between 0 and 400C.

dans laquelle R4 a les mimes significations que dans la formule (I).The derivatives of formula (V) can also be obtained by the action of a derivative of formula (IX) on a derivative of formula

in which R4 has the same meanings as in formula (I).

 This reaction is generally carried out in an inert solvent such as acetonitrile, dimethylformamide or tetrahydrofuran, in the presence of a base such as an alkali metal hydride at a temperature in the region of 200C.

 The derivatives of formula (XIII) can be obtained by the action of an amine of formula (VIII) on a chloride of formula (VII).

This reaction is generally carried out in an inert solvent such as a chlorinated solvent (chloroform, dichlorc-1, 2 ethane for example), in the presence of a base such as a tertiary amine
Triethylamine, at a temperature close to 20 C.

dans laquelle R1, R2 et R4 ont les mêmes significations que dans la formule (I).The derivatives of formula (V) can also be obtained by the action of phthalimide potassium hydroxide on a derivative of formula

in which R1, R2 and R4 have the same meanings as in formula (I).

 This reaction is carried out in an inert solvent such as dimethylformamide, at a temperature in the region of 100 C.

The derivative of formula (XIV) can be obtained by the action of an amine of formula (Vl) on a chlorinated derivative of formula
ClCO-CH2-Cl (XV)
This reaction is carried out in an inert solvent such as dimethylformamide, tetrahydrofuran or a chlorinated solvent, in the presence of a tertiary amine such as triethylamine, at a temperature between 10 and 80 C.

The compounds of formula (I) for which R3 represents a phenylamino radical whose phenyl ring is optionally substituted can also be prepared by the action of an amine of formula (VI) on an acid of formula
HOOC-CH2-NH-CO-R3 (XVI) in which R3 has the same meanings as in formula (I) ce a reactive derivative of this acid.

 This reaction is generally carried out under the conditions mentioned above for the reaction of the acids of formula (xI) with an amine of formula (XII).

 The acids of formula (XVI) can be obtained by the action of an isocyanate of formula (II) on glycine.

 This reaction is generally carried out in aqueous solution, in the presence of a base such as an alkali metal bicarbonate, at a temperature in the region of 20 ° C.

dans laquelle R1, R2 et R4 ont les mêmes significations que dans la formule (I), sur un dérivé de formule
H2N-R9 (xx) dans laquelle Rg représente un radical phényle éventuellement substitué par un ce plusieurs substituants choisis parmi les atanes d'halogène, les radicaux alkyle, alccxy et alkylthio.The compounds of formula (I) for which R3 represents an optionally substituted phenylamino radical can also be prepared by the action of a derivative of formula

in which R1, R2 and R4 have the same meanings as in formula (I), on a derivative of formula
H2N-R9 (xx) in which Rg represents a phenyl radical optionally substituted by a ce several substituents chosen from halogen atanes, alkyl, alkyl and alkylthio radicals.

 This reaction is generally carried out in an inert solvent such as tetrahydrofuran, dimethylformamide, a chlorinated solvent w an aratiatic solvent, at a temperature between 20 C and the boiling point of the solvent.

The substituted anilines of formula (Xx) can be obtained by application or adaptation of the method described by
R.SCHRÖTER, Methoden der Organischen Chemie, Houber Weil, Band
XI / 1, p. 360.

 The derivatives of formula (XVII) can be obtained by the action of a derivative of formula (III) on the N, N-diimidazole carbonyl.

 This reaction is generally carried out in an inert solvent such as tetrahydrofuran, dimethylformamide, a chlorinated solvent or an aranatic solvent, at a temperature between 200C and the boiling point of the solvent.

The compounds of formula (I) for which R3 represents an optionally substituted phenyl, naphthyl, indolyl or quinolyl radical can be prepared by the action of a derivative of formula (III) on an acid of formula
HCOC-R3 (XIX) in which R3 has the same meanings as previously, w a reactive derivative of this acid.

 This reaction is generally carried out under the conditions described above for the reaction of an acid of formula (XI) with an amine of formula (XII).

 It is understood by a person skilled in the art that, for the implementation of the methods according to the invention described above, it may be necessary to introduce groups which protect amino functions in order to avoid side reactions. These functions can for example be blocked in the form of trifluoromethylacetamide then regenerated by the action of ammoniacal methanol after having implemented the process according to the invention.

The enantianers of the compounds of formula (I) containing at least one asymmetric center can be obtained by resolution of the racemates, for example by chromabography on a chiral column according to WH PIRE et al., Asymetric synthesis, vol. 1, Academic
Press (1983) or by synthesis from chiral precursors.

 The compounds of formula (I) can be purified by the usual known methods, for example, by crystallization, chromatography, extraction, etc.

 The compounds of formula (I) have interesting pharmacological properties. These compounds have a strong affinity for cholecystokinin receptors (CCK) and are therefore useful in the treatment and prevention of disorders related to CCK in the nervous system and the gastrointestinal tract.

 Thus, these compounds can be used for the treatment or prevention of psychoses, anxiety disorders, Parkinson's disease, tardive diskinesia, syndreas of the irritable colon, acute pancreatitis, ulcers, disorders intestinal motility, certain tumors of the lower esophagus, colon and intestine and appetite regulating alarm.

 These compounds also have a potentiating effect on the analgesic activity of narcotic and non-narcotic drugs.

The affinity of the compounds of formula (I) for the receptors
CCK was determined using a technique inspired by that of S.

 5AITO et al. (J. Neuro. Chem., 37, 483-490 (1981)) at the level of the cerebral cortex and at the level of the pancreas.

 In these tests the IC50 of the compounds of formula (1) is generally equal to less than 1000 nM.

 The compounds of formula (I) exhibit low toxicity.

The LD50 is generally greater than 40 mg / kg subcutaneously in mice.

Of particular interest are the compounds of formula (I) for which:
- R1 represents a hydrogen atane,
R2 represents an alkoxy radical or a -NR5R6 chain in which R5 and R6, which are identical or different, represent an alkyl or phenyl radical,
R3 represents a phenylamino radical (the phenyl nucleus of which is optionally substituted by one or more substituents chosen from the alkyl and alkythio radicals) w indolyl,
R4 represents a phenyl radical substituted by one or more substituents chosen from halogen atanes and alkyl, alkoxy, dialkylamino, nitro, alkylthio, alkoxycarbonyl, acylamino, trifluoromethyl, methylenedioxy, trifluoromethoxy and trifluoromethylthio radicals.

The preferred compounds are:
- [[(3-methylphenyl) -3 ureido] -2 N- (3-methoxyphenyl) -acetamido] -2 N-methyl N-phenyl-acetamide
- [[(3-methylphenyl) -3 ureido] -2 N- (2-chloro-phenyl) -acetamido] -2 N-methyl N-phenyl-acetamide
- [[(3-methylphenyl) -3 ureido] -2 N- (2-ethoxycarbonylphenyl) -acetamido] -2 tert-butyl acetate
- [[(3-methylphenyl) -3 ureido] -2 N- (acethylenedioxy-3,4 $ phenyl) -acetamido] -2 phenyl) -acetamido] -2 tert-butyl acetate
- [[(3-methylphenyl) -3 ureidol-2 [N- (2-chloro-phenyl) -acetamido] -2 tert-butyl acetate
- [[(3-methylphenyl) -3 ureido] -2 N- (4-methoxyphenyl-acetamido] -2 tert-butyl acetate
- ([(3-methylphenyl) -3 ureido] -2 N- (3,4-methylenedioxyphenyl) -acetamido] -2 tert-butyl acetate
- [N- (4-chloro-phenyl) ((3-methylphenyl) -3 ureido] -2 acetamido] -2 tert-butyl acetate
- [N- (4-dimethylphenyl) [(3-methylthio phenyl) -3 ureido] -2 acetamido] -2 tert-butyl acetate
- [[(3-methylphenyl) -3 ureido] -2 N- (2-methoxyphenyl) -acetamido] -2 tert-butyl acetate
- [[(3-methylphenyl) -3 ureido] -2 N- (2-methylphenyl) -acetamido] -2 tert-butyl acetate
- [[(3-methyl-3-phenyl ureidoj-2 N- (2,3-dichloro-phenyl) -acetamido] -2 tert-butyl acetate
The following examples illustrate the invention without limiting it.

EXAMPLE 1
To a solution of 1.25 g of [amino-2 N- (3-chloro-phenyl) acetamido] -2 tert-butyl acetate in 20 cm3 of anhydrous tetrahydrofuran, 0.6 is added, at a temperature of 200C g of 3-methylphenyl isocyanate. The solution obtained is stirred for 4 hours at a temperature in the region of 200C and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The residual oil is purified by chranatography on 150 g of silica (0.063-0.2 mm ) contained in a column 2 cm in diameter [eluent ethyl cyclohexaneacetane (75-25 by volume)] by collecting fractions of 20 cm3. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. After crystallization from diisopropyl ether, 0.8 g of [[(3-methylphenyl) -3 ureido] -2 N- (3-chloro-phen-yl) -acetamidoj-2 acetate tert-butyl acetate is obtained. at 1 1 00C.

 [Amino-2 N- (3-chloro-phenyl) -acetamido] -2 tert-butyl acetate can be prepared as follows: to a solution of 2.4 g of [phthalimido-2 N- (chloro- 3 phenyl) -acetamido] 2 tert-butyl acetate in 40 cm3 of methanol, 0.75 g of hydrazine hydrate is added. The reaction mixture is stirred at reflux for 3 hours and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The residue is stirred with 100 cm3 of diethyl ether then the insoluble product is separated by filtration and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 1.3 g of 2-ramino-3-chloro-phenyl) -acetamido-2-tert-butyl acetate are thus obtained in the form of an oil used as it is in the subsequent syntheses.

 [Phthalimido-2 N- (3-chloro-phenyl) -acetamido-2 tert-butyl acetate can be prepared in the following manner: to a solution of 4.8 g of (3-chloro-phenyl) amino-2 acetate tert-butyl in 60 cm3 of 1,2-dichloroethane, maintained under an argon atmosphere, 2.8 g of triethylamine are added and then dropwise, at a temperature in the region of 200C, a solution of 6.2 g of phthalimido chloride -2 acetyl in 20 cm3 of 1,2-dichloroethane. The solution obtained is stirred for 3 hours at a temperature close to 200C, then added with 50 cm3 of distilled water. The aqueous phase is separated by decantation and then re-extracted with 2 times 50 cm3 of dichlor> 1.2 ethane. The organic phases are combined, washed with 2 times 10 year 3 of distilled water, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The oil obtained is purified by chromatography on 200 g of silica (0.063-0.2 mm) contained in a column 2.5 years in diameter [eluent cyclohexane-ethyl acetate (50-50 by volume)] while collecting 25 year fractions 3. Fractions 3 to 7 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400 C. This gives 2.6 g of [phthalimido-2 N (3-chloro-phenyl) -acetamido] 2 tert-acetate butyl in the form of an oil used as it is in subsequent syntheses.

 Tert-butyl (3-chloro-phenyl) arn2 acetate can be prepared as follows: 5.9 g of bromoacetate are added to a solution of 7.6 g of 3-chloro aniline in 60 cm 3 of acetonitrile tert-butyl. The solution obtained is stirred at reflux for 4 hours. After cooling, the insoluble product is separated by filtration and washed with 30 cm 3 of acetonitrile. The filtrates are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40 ° C. The residual oil is dissolved in 150 cm3 of dichloroethane and the solution obtained is washed with 4 times 15 cm3 of distilled water. The organic phase is dried over magnesium sulfate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) at 400 C. This gives 8.1 g of (3-chloro-phenyl) 2-amino tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

 Phthalimido-2 acetyl chloride can be prepared according to the method described by W. GRASSMANN and E. SCHULTE-UEBBING, Chem.

Ber., 83, 244-247, (1950).

EXAMPLE 2
By operating in a manner analogous to that described in Example 1, but starting with 2.5 g of [2-amino-N- (2-fluomphenyl) -acetamido] -2 tert-butyl acetate and 1.2 g of 3-methylphenyl isocyanate, after recrystallization from diisopropyl ether, 1.75 g of [[(3-methylphenyl) -3 ureido] -2 N- (2-fluoro-phenyl) are obtained ) -acetamido] -2 tert-butyl acetate melting at 1480C.

 T-butyl [2-amino-N- (2-fluoro-phenyl) -acetamido] -2 acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [2-amino N- (3-chloro-phenyl) -acetamidol-2 tert-butyl acetate, but from 4.9 g of [phthalimido-2 N (2-fluoro-phenyl) -acetamido] -2 tert-butyl acetate and 0, 77 g of hydrazine hydrate. 2.7 g of [2-amino-2- (fluoro-phenyl) -acetamido] -2 tert-butyl acetate were thus obtained in the form of an oil used as it is in the subsequent syntheses.

 [Phthalimido-2 N (2-fluoro-phenyl) -acetamido] -2 tert-butyl acetate can be prepared as follows: to a solution of 3.3 g of (2-fluoro-phenylamino) -2 tert-acetate -butyl in 60 cm of 1,2-dichloroethane, maintained under an argon atmosphere, 1.3 g of sodium hydrogen carbonate are added and then dropwise, at a temperature in the region of 200C, a solution of 3.1 g 2-phthalimido acetyl chloride in 10 cm3 of 1,2-dichloroethane. The solution obtained is stirred for 3 hours at a temperature close to 200C, then added with 20 cm3 of distilled water. The aqueous phase is separated by decantation and then reextracted with 2 times 100 cm3 of 1,2-dichloroethane. The uranic phases are combined, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. There is thus obtained, after recrystallization from petroleum ether, 4.9 g of [phthalimido-2 N- (2-fluoro-phenyl) acetamidoi-2 tert-butyl acetate fcndant at 1400C.

 Tert-butyl (2-fluoro-phenyl) amino-2 acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of tert-butyl acetate (3-chloro-phenylamino) -2 acetate, but from 2.45 g of 2-fluoro aniline and 1.95 g of tert-butyl bromoacetate. 1.1 g of (2-fluoro-phenyl) 2-amino-tert-butyl acetate, thus melting at 700C, are obtained after recrystallization from petroleum ether.

EXAMPLE 3
By operating in a manner analogous to that described in Example 1, but starting from 6.6 g of [2-amino-N- (4-methoxyphenyl) -acetamido] -2 tert-butyl acetate and 3 g of 3-methylphenyl isocyanate, after recrystallization from acetonitrile, 1.7 g of [[(3-methylphenyl) -3 ureido] -2 N (4-methoxyphenyl) -acetamido] are obtained - 2 tert-butyl acetate melting at 1580C.

 [2-Amino-N- [4-methoxyphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [2-amino N- (3-chloro-phenyl) -acetamido] -2 tert-butyl acetate, but from 11.7 g of [phthalimido-2 N- (4-methoxyphenyl) -acetamido] -2 tert-acetate butyl and 1.75 g of hydrazine hydrate. 7 g of [2-amino-N- (4-methoxyphenyl) -acetamido] 2 tert-butyl acetate were thus obtained in the form of an oil used as it is in the subsequent syntheses.

[Phthalimido-2 N- (4-methoxyphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 2 for the preparation of [phthalimido-2
N- (2-fluorophenyl) -acetamido] -2 tert-butyl acetate, but from 6.7 g of (4-methacyphenylamino) -2 tert-butyl acetate of 2.5 g of hydrogen carbonate sodium and 6.25 g of 2-phthalimido acetyl chloride. 11.7 g of [phthalimido-2 N (4-methoxyphenyl) -acetamido] -2 tert-butyl acetate were thus obtained in the form of an oil used as it is in subsequent syntheses.

 Tertiary butyl (4-methoxyphenyl) amino-2 acetate can be prepared in a similar manner to that described in Example 1 for the preparation of tert-butyl acetate-3 phenyl) 2-amino acetate, but from 7.3 g of 4-methoxy aniline and 5.95 g of tert-butyl bromoacetate. 7.2 g of (methoxy-4-phenyl) amino-2-tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 4
By operating in a manner analogous to that described in Example 1, but starting from 2 g of [2-amino-N- (2-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate and 0, 8 g of 3-methylphenyl isocyanate, after recrystallization from ethyl acetate, 1.35 g of [[(3-methylphenyl) -3 ureido] -2 N- (2-trifluoromethoxyphenyl) is obtained -acetamido] -2 tert-butyl acetate cracking at 1630C.

 [2-Amino-2 N- (2-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate can be prepared as follows: to a solution of 4.4 g of [2-phthalimido-N- (trifluoromethoxy- 2 phenyl) -acetamido] -2 tert-butyl acetate in 50 cm3 of ethanol, 1.5 g of hydrazine hydrate are added. The reaction mixture is stirred for 3 hours at a temperature in the region of 200C and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The residue is stirred with 200 cm 3 of diethyl ether and the insoluble product is separated by filtration. The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 2.1 g of [amino-2 N- (2-trifluoromethoxy-phenyl) -acetamido] -2 tert-butyl acetate were thus obtained in the form of an oil used as it is in subsequent syntheses.

 [2-phthalimido-N- (2-trifluoromethoxy-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in the following manner: to a solution of 5 g of 2-phthalimido-N- (2-trifluoromethoxy-phenyl) acetamide in 50 cm3 of anhydrous tetrahydrofuran maintained under an argon atmosphere, ai added at a temperature close to 100C, 0.7 g of an oily suspension (50% by weight) of sodium hydride and stirred the suspension obtained for 1 hour at a temperature in the region of 20 C. A solution of 2.75 g of tert-butyl bromoacetate in 10 cm 3 of anhydrous tetrahydrofuran is then added and stirring is continued for 3 hours at a temperature in the region of 200 C. The mixture The reaction is then poured into a mixture cooled to a temperature close to OOC, 20 cm 3 of distilled water and 200 cm 3 of ethyl acetate. The aqueous phase is separated by decantation and reextracted with 2 times 20 cm of ethyl acetate. The organic phases are combined, washed with 3 times 25 cm of distilled water, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 4.4 g of [phthalimido-2 n- (2-trifluoromethoxy-phenyl) acetamido 2 tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

 Phthalimido-2 N- (2-trifluoromethoxy-phenyl) -acetamide can be prepared as follows: to a solution of 3.6 g of 2-trifluoranethoxy-aniline in 50 cm3 of dichloroethane maintained under an argon atmosphere, an add 2 , 2 g of triethylamine then maintaining the temperature in the vicinity of 200C, a solution of 4.6 g of 2-phthalimido acetyl chloride in 25 cm3 of dichloromethane. The solution obtained is stirred for 3 hours at a temperature close to 200C, then added with 25 years of distilled water. The solid formed is separated by filtration, washed with 3 times 5 cm of dichloromethane and then with 3 times 10 cm3 of distilled water and air-dried. The organic phase of the filtrate is separated by decantation, washed with 2 times 10 years 3 d distilled water, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The solid obtained is combined with the previous one and the whole is recrystallized from ethyl acetate.

5.1 g of phthalimido-2 N- (2-trifluoranethoxy-phenyl) -acetsmide thus melting at 1920C are obtained.

EXAMPLE 5
By operating in a manner analogous to that described in Example 1, but starting from 3.4 g of [2-amino-N- (3-trifluo thoxy-phenyl) -acetamido] -2 teet-butyl acetate and 1.4 g of 3-methylphenyl isocyanate, after recrystallization from diisopropyl ether, 1.75 g of [[(3-methylphenyl) -3 ureido] -2 N- (trifluoromethoxy-3) are obtained phenyl) -acetamido] -2 teet-butyl acetate melting at 1250C.

[2-Amino-N- (3-trifluoromethoxy-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [2-amino
N- (2-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate, but from 3 g of [phthalimido-2 N- (3-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate and 3.2 g of hydrazine hydrate. thus obtained 3.5 g of [amino-2
N- (3-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

 [Phthalimido-2 N- (3-trifluoromethoxy-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [phthalimido-2 (trifluoromethoxy- 3 phenyl) -acetamido] -2 tert-butyl acetate, but from 4.8 g of phthalimido-2 N- (3-trifluoromethoxyphenyl) -acetamide, 0.7 g of an oily suspension (50% by weight) of sodium hydride and 2.75 g of tert-butyl bromoacetate. ai thus obtains 5.1 g of [phthalimido 2 N- (trifluoro-3-methoxyphenyl) -acétmido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

 Phthalimido-2 N- (3-trifluoromethoxy-phenyl-acetamide can be prepared in a similar manner to that described in Example 4 for the preparation of phthalimido-2 N- (trifluoromethoxy-2-phenyl) -acetamide, but starting from 3.6 g of trifluorcmethoxy-3 aniline, 2.2 g of triethylamine and 4.6 of phthalimido-2 acetyl chloride. Thus, after recrystallization from ethyl acetate, 4.8 g of phthalimido-2 N- (trifluoranethoxy-3-phenyl) -acetamide melting at 1700C.

EXAMPLE 6
By managing in a manner analogous to that described in Example 1, but starting from 3.1 g of [2-amino-N- (3-methylphenyl) -acetamidoj-2 acetate of tert-butyl and 0 , 52 g of 3-methylphenyl isocyanate, after recrystallization from diiscpropyl ether, 1.2 g of [[(3-methylphenyl) -3 ureido] -2 N- (methyl-3-phenyl) are obtained ) -acetamido] -2 tert-butyl acetate melting at 970C.

[2-Amino-N- (3-methylphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [2-amino
N- (2-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate, but from 7.5 g of [phtSlimido-2 N- (3-methylphenyl) acetamido] -2 tert-butyl acetate and 1.84 g of hydrazine hydrate. 3.5 g of [amire2 N- (3-methylphenyl) acetamido] -2 tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

 [Phthalimido-2 N- (3-methylphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [phthalimido-2 N- ( tri-fluoranethoxy-2 phenyl) -acetamido] -2 tert-butyl acetate, but from 12.5 g of phthalimido-2 N- (3-methylphenyl) acetamide, 2.45 g of an oily suspension ( 50% by weight) of sodium hydride and 8.3 g of tert-butyl bromoacetate. There is thus obtained, after recrystallization from diisopropyl ether, 7.6 g of [phthalimido-2 N- (3-methylphenyl) aceta mido] -2 tert-butyl acetate melting at 1660C.

 Phthalimido-2 N- (methyl-3phenyl) -acetamide can be prepared in a manner analogous to that described in Example 4 for the preparation of phthalimido-2 N- (2-trifluoromethoxy-phenyl) -acetamide, but starting from 5.36 g of 3-methyl aniline, 5.1 g of triethylamine and 11.2 g of phthalimido2 acetyl chloride. 12.7 g of phthalimido-2 N- (3-methylphenyl) -acetamide are thus obtained, melting at 207 C.

EXAMPLE 7
And operating in a manner analogous to that described in Example 1, but starting from 1.6 g of [2-amino-N- (3-methoxyphenyl) -acetamido] -2 N-methyl N-phenyl- acetamide and 0.67 g of 3-methylphenyl isocyanate, after recrystallization from acetonitrile, 1.2 g of [[(3-methylphenyl) -3 ureido] -2 N- (3-methoxyphenyl) are obtained ) -acetamido] -2 N-methyl
N-phenyl-acetamide melting at 1790C.

[2-Amino-N- (3-methoxyphenyl) -acetamido] -2 N-methyl
N-phenyl-acetamide can be prepared in a similar manner to that described in Example 4 for the preparation of [2-amino-N- (2-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate, but from 2.3 g of [phthalimido-2 N- (3-methoxyphenyl) -acetamidoj-2
N-methyl N-phenyl-acetamide, and 0.75 g of hydrazine hydrate. 1.6 g of [2-amino-N- (3-methoxyphenyl) -acetamido] -2 are thus obtained.
N-methyl N-phenyl acetamide in the form of an oil used as it is in subsequent syntheses.

[Phthalimido-2 N- (3-methoxyphenyl) -acetamido-2 N-methyl
N-phenyl-acetamide can be prepared in a manner analogous to that described in Example 4 for the preparation of [phthalimido-2
N- (2-trifluoromethoxy-phenyl) -acetamido] -2 tert-butyl acetate, but from 9.15 g of phthalimido-2 N- (3-methoxyphenyl) -acetamide, of 1.6 g of a oily suspension (50% by weight) of sodium hydride and 7.4 g of 2-bromo-N-methyl,
N-phenyl-acetamide. thus obtained 5.7 g of [phthalimido-2
N- (3-methoxyphenyl) -acetamide] -2 N-methyl N-phenyl-acetamide in the form of a paste used as it is in subsequent syntheses.

 Pthalimido-2 N- (3-methayphenyl) -acetamide can be prepared in a manner analogous to that described in Example 4 for the preparation of phthalimido-2 N- (2-trifluoromethoxy-phenyl) -acetamide, but at from 6.15 g of 3-methoxy aniline, 5.6 g of triethylamine and 11.2 g of 2-phthalimido acetyl chloride. 12.3 g of phthalimido-2 2 N- (3-methoxyphenyl) -acetamide, melting at 1860C, were thus obtained, after recrystallization from acetonitrile.

EXAMPLE 8
Having in a manner analogous to that described in Example 1, but starting with 4.9 g of 2-amino-N- (3-trifluormiethyl-phenyl) acetamido] -2 tert-butyl acetate and 2 g of 3-methylphenyl isocyanate, 1.56 g of [[(3-methylphenyl) -3 ureidol-2) are obtained after recrystallization from diisopropyl ether
N- (3-trifluoromethyl phenyl) -acetamido] -2 tert-butyl acetate melting at 1400C.

[2-amino-N- (3-trifluoromethyl-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [2-amino
N- (2-trifluoromethylphenyl) -acetamido] -2 tert-butyl acetate, but from 9 g of [phthalimid> 2 N- (3-triflucranethylphenyl) -acetamido] -2 tert-butyl acetate and 2.9 g of hydrazine hydrate. 5.2 g of [amino-2 N- (3-trifluoromethyl-phenyl) -acetamido] -2 tert-butyl acetate were thus obtained in the form of an oil used as it is in the subsequent syntheses.

[2-phthalimido-N- (3-trifluoromethyl phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of (2-phthalimido-N 2-trifluanethoxyphenyl) -acetamido] -2 tert-butyl aaetate, but from 16.5 g of phthalimino-2 N- (trifluoromethyl-3-phenyl) -acetamide, 2.3 g of an oily suspension ( 50% by weight) of sodium hydride and 9.2 g of tert-butyl branoacetate, thus obtaining 9.1 g of [phthalimido-2
N- (3-trifluoromethyl phenyl) -acetamido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

Phthalimido-2 N- (3-trifluoromethyl-phenyl) acetamide can be prepared in a manner analogous to that described in Example 4 for the preparation of phthalimido-2 N- (2-trifluoromethoxy-phenyl) -acetamide, but starting from 8.1 g of 3-trifluocmethyl aniline, 5.1 g of triethylamine and 11.2 g of 2-phthalimido acetyl chloride. This gives 16.7 g of phthalimido-2
N- (3-trifluoromethyl phenyl) -acetamide melting at 235 C.

EXAMPLE 9
By operating in a manner analogous to that described in Example 1 but starting from 3.6 g of [2-amino-N- (2-ethoxycarbonylphenyl) -acetamido] -2 tert-butyl acetate and 1 , 42 g of 3-methylphenyl isocyanate, after recrystallization from diisopropyl ether, 1.35 g of [r (3-methylphenyl) -3 ureido] -2 N- (2-ethoxycarbonylphenyl) are obtained -acetamido] -2 tert-butyl acetate melting at 1420C.

[2-Amino-N- (2-ethoxycarbonylphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [2-amino
N- (3-trifluoromethyl phenyl) -acetamido] -2 tert-butyl acetate, but from 6.13 g of [phthalimido-2 N- (2-ethoxycarbonyl phenyl) -acetamido] -2 tert-butyl acetate and 1.98 g of hydrazine hydrate. oe thus obtains 3.6 g of [2-amino-N- (2-ethoxycarbonylphenyl) -acetamido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

[2-phthalimido-N- (2-ethoxycarbonyl phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [phthalimido-2
N- (2-trifluoromethylphenyl) -acetamido] -2 tert-butyl acetate, but from- 7.7 g of phthalimido-2 N- (2-ethoxycarbonyl phenyl) -acetamide, of 1.26 g of an oily suspension (50% by weight) of sodium hydride and 4.3 g of tert-butyl bromoacetate. 6.1 g of [phthalimido-2 N- (2-ethoxycabonylphenyl) -acetamido] -2 tert-butyl acetate, melting at 1270C, are thus obtained, after recrystallization from diisopropyl ether.

Phthalimido-2 N- (2-ethoxycarbonylphenyl) -acetamide can be prepared in a manner analogous to that described in Example 4 for the preparation of phthalimido-2 N- (2-trifluoromethoxy-phenyl) -acetamide, but at from 4.13 g of ethyl 2-amino benzoate, 2.8 g of triethylamine and 5.6 g of 2-phthalimido acetyl chloride. 7.7 g of phthalimido-2 are thus obtained
N- (2-ethoxycarbonylphenyl) -acetamide melting at 187 ° C.

EXAMPLE 10
By operating in a manner analogous to that described in Example 1, but starting from 4.7 g of d1 [2-amino-N- (2-acetylamino phenyl) -acetamido] -2 tert-butyl acetate and 2 g of 3-methylphenyl isocyanate, 3.6 g of ([(3-methylphenyl) -3 ureido] -2) are obtained after recrystallization from ethyl acetate
N- (2-acetylamino phenyl) -acetamido] -2 tert-butyl acetate melting at 1850C.

[2-Amino-2N- (2-acetyl-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [2-amino
N- (2-trifluoromethylphenyl) -acetamido] -2 tert-butyl acetate, but from 7.2 g of [phthalimido-2 N- (2-acetylamino phenyl) -acetamido] -2 tert-butyl acetate and 2.4 g of hydrazine hydrate. 4.8 g of [2-amino-N- (2-acetylamino-phenyl) -acetamido] -2 tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

[2-phthalimido-N- (2-acetylamino phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 4 for the preparation of [phthalimido-2
N- (2-trifluoromethylphenyl) -acetamido] -2 tert-butyl acetate, but from 9.7 g of phthalimido-2 N- (2-acetylamino phenyl) acetamide, from 1.6 g of a suspension oily (50% by weight) of sodium hydride and 5.85 g of tert-butyl bromoacetate. 8 g of [phthalimido-2 N- (2-acetylamino-phenyl) -acetamido] -2 teet-butyl acetate, melting at 1,700C, are thus obtained, after recrystallization from ethyl acetate.

 Phthalimido-2N- (acetylamino-2 phenyl) -acetamide can be prepared in a manner analogous to that described in Example 4 for the preparation of ptalimido-2 N- (tri fluoranethoxy-2-phenyl) acetamide, but starting from 6 g of 2-acetylamino aniline, 4.05 g of triethylamine and 9.6 g of 2-phthalimido acetyl chloride.

 12.5 g of phthalimido-2 N- (2-acetylamino-phenyl) acetamide were thus obtained, melting at 2700C.

EXAMPLE 11
By operating in a manner analogous to that described in Example 1, but starting from 4.8 g of [2-amino-N- (2-chloro-penyl) -acetamido] -2 tert-butyl acetate and 2.35 g of 3-methylphenyl isocyanate, after recrystallization from a mixture of ethyl acetate and methanol (80-20 by volume), 1.4 g of r [(3-methyl-penyl) are obtained -3 ureido] -2 N- (2-chloro phenyl) -acetamido] -2 tert-butyl acetate melting at 1480C.

 [Amino-3 N- (2-chloro-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [Amino-2 N- (3-chloro-phenyl) -acetamido] -2 tert-butyl acetate, but from 9.12 g of [phthalimido-2 N- (2-chloro-phenyl) -acetamido] -2 tert-butyl acetate and 1 g of hydrazine hydrate. 5.2 g of [amino-2 N- (2-chloro-phenyl) -acetamido] -2 tert-butyl acetate were thus obtained in the form of an oil used as such in the subsequent syntheses.

[Phthalimido-2 N- (2-chloro-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 2 for the preparation of [phthalimido-2
N- (fluoro 2 ppenyl) -acetamido] -2 tert-butyl acetate, but from 8 g of (2-chloro-phenyl) 2-amino tert-butyl acetate, 3.1 g of sodium hydrogen carbonate and 7.4 g of 2-phthalimido acetyl chloride. After recrystallization from a mixture of ethyl acetate and cyclohexane (70-30 by volume), 10.6 g of [phthalimido-2 N- (2-chloro-phenyl) -acetamido] -2 tert acetate are obtained -butyle melting at 1 640C.

 Tert-butyl (2-chloro-phenyl) amino-2 acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of tert-butyl (3-chloro-phenyl) amino-acetate, but from 19.1 g of 2-chloro aniline and 9.75 g of tert-butyl bromoacetate. This gives 9.3 g of (2-chloro-phenyl) 2-amino tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 12
By following a procedure analogous to that described in Example 1, but starting from 2.4 g of [2-amino-N- (3,4-methylenedioxyphenyl) -acetamido] -2 tert acetate -butyl and 1 g of 3-methylphenyl isocyanate, ai obtained after recrystallization from ethyl acetate, 1.65 g of [[(3-methylphenyl) -3 ureido] -2 N (methylenedioxy- 3,4 phenyl) -acetamido] -2 tert-butyl acetate melting at 1420C.

[Amino-2 N- (3,4-methylenedioxyphenyl) -acetamido] -2 test-butyl acetate can be prepared as follows: to a solution of 4.6 g of [phthalimido-2 N- ( methylenedioxy-3,4-phenyl) -acetamidoj-2 tert-butyl acetate in 70 cm3 of dichloromethane, 1.45 g of methylhydrazine are added at a temperature close to OOC. The reaction mixture is stirred for 16 hours at a temperature close to 200C then for 2 hours at reflux of the dichloeanethaae and cooled to a temperature close to 200C. 50 cm3 of distilled water are added, the mixture is stirred and the aqueous phase is separated by decantation, which is reextracted with 2 times 40 cm3 of dichloromethane. The organic phases are combined, dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400 C. The oil obtained is purified by chromatography on 50 g of silica (0.063-0.2 mm) contained in a column 2 years in diameter [eluent: ethyl acetate-methanol (90-10 in volumes)] by collecting fractions of 20 cm3. Fractions 11 to 22 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 1.85 g of [2-amino] are thus obtained
N- (3,4-methylenedioxyphenyl) -acetamido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

[Phthalimido-2 N- (methylenedioxy-3,4-phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 2 for the preparation of [phthalimi2
N- (2-fluoro phenyl) -acetamido) -2 tert-butyl acetate, but from 5.15 g of (methylenedioxy-3,4-phenyl) 2-amino tert-butyl acetate, 1.9 g sodium hydrogen carbonate and 4.6 g of 2-phthalimido acetyl chloride. After recrystallization from ethyl acetate, 8 g of [phthalimido-2 N- (methylenedioxy-3,4-phenyl) acetamido] -2 tert-butyl acetate, melting at 1660C, are obtained.

 Tertiary-butyl (3,4-methylenedioxyphenyl) amino-2 acetate can be prepared in a similar manner to that described in Example 1 for the preparation of tert-butyl acetate (3-chloro-phenylamino) -2 , but from 9 g of 3,4-methylenedioxy aniline and 5.9 g of tert-butyl bromoacetate. There is thus obtained, after recrystallization from petroleum ether, 5.2 g of (methylededioxy-3,4-phenyl) 2-amino tert-butyl acetate melting at 800C.

EXAMPLE 13
To a solution of 0.7 g of [2-amino-N- (4-dimethylamino phenyl) -acetamido] -2 tert-butyl acetate in 15 cm3 of anhydrous tetrahydrofuran, is added, at a temperature in the region of 200C, 0v , 35 g of 3-methylphenyl isocyanate. The solution obtained is stirred for 3 hours at a temperature in the region of 200C and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. After recrystallization of the residual solid from ethyl acetate, 0.7 g of t [(3-methylphenyl) -3 ureidol] -2 N- (4-dimethylamino phenyl) -acetamido] -2 tert acetate is obtained. -butyle melting at 1050C.

[2-Amino-N- (4-dimethylamino-phenyl) -acetamido] -2 tert-butyl acetate can be prepared as follows: to a solution of 1 g of [phthalimido-2 N- (4-dimethylamino-phenyl) ) -acetamido] -2 tert-butyl acetate in 20 years of methanol, ai added 0.15 g of hydrazine hydrate. The reaction mixture is stirred at reflux for 3 hours and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The residue is stirred with 75 cm 3 of diethyl ether and the insoluble product is separated by filtration. The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) at 400C. This gives 0.7 g of [2-amino
N- (4-dimethylamino phenyl) -acetamido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

[2-phthalimido-N- (4-dimethylamino phenyl) -acetamido] -2 tert-butyl acetate can be prepared in the following manner: to a solution of 2.6 g of (4-dimethylamino phenyl) 2-amino acetate of tert-butyl in 20 cm3 of 1,2-dichloroethane, maintained under an argon atmosphere, 1.4 g of triethylamine are added then dropwise, at a temperature in the region of 200C, a solution of 3.1 g of 2-phthalimido acetyl chloride in 20 cm of 1,2-dichloroethane. The solution obtained is stirred for 3 hours at a temperature close to 200C, then added with 25 cm of distilled water. The aqueous phase is separated by decantation and then re-treated with 2 times 50 cm3 of 1,2-dichloroethane. The organic phases are combined, washed with 2 times 10 cm3 of distilled water, dried over magnesium sulfate, filtered and then accentuated to dryness. under reduced pressure (2.7 kpa) at 400C. The oil obtained is purified by chromatography on 100 g of silica (0.063-0.2 mm) contained in a 2-year-old colone in diameter Celuant dichloromethane-methanol (98-2 in volumes)], collecting 15 cm 3 fractions. The fractions containing only the sought product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 1.1 g of [phthalimido-2 was thus obtained
N- (4-dimethylamino phenyl) -acetamido] -2 tert-butyl acetate melting at 1700C.

 Tert-butyl (4-dimethylamino-phenyl) amino-2 acetate can be prepared in the following manner: to a suspension of 6.3 g of 4-dimethylamino aniline dihydrochloride in 50 cm 3 of acetonitrile, is added to a temperature in the region of 10 ° C., 6.1 g of triethylamine. The suspension obtained is stirred for 30 minutes at a temperature in the region of 200C, then 3 g of tert-butyl bromoacetate are added and the reaction mixture is stirred at reflux for 4 hours. After cooling, the insoluble product is separated by filtration and washed with 15 cm of acetonitrile. The combined salit filtrates and concentrated to dryness under reduced pressure (2.7 kPa) at 40 C. The residual oil is dissolved in 100 cm3 of dichloromethane and the solution obtained is washed with 4 times 10 cm3 of distilled water. The organic phase is dried with magnesium sulphate, filtered, then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 2.6 g of (dimethylamino-4-phenyl) amino-2-tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 14
By operating in a manner analogous to that described in Example 11, but starting from 5.1 g of [2-amino-N- (3-methylthio-phenyl) -acetamido] -2 tert-butyl acetate and 2.2 g of 3-methylphenyl isocyanate, after recrystal lisatiai in a mixture of diisopropyl ether and ethyl acetate (80-20 by volume), 2.6 g of [[(methyl -3 phenyl) -3 ureido-2 N- (3-methylthio phenyl) -acetamido] -2 tert-butyl acetate melting at 1350C.

[2-Amino-N- (methylthi3 phenyl) - acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [2-amino-N- (3-chloro-phenyl) -acetamido] -2 tert-butyl acetate, but from 7.6 g of [phthalimido-2 N- (3-methylthio phenyl) -acetamido] -2 tert-butyl acetate, 2.6 g of hydrazine hydrate and operating at a temperature in the region of 200C. 5.1 g of [amino-2 were thus obtained
N- (3-methylthio phenyl) -acetamido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

[Phthalimido-2 N- (3-methylthio phenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [phthalimido-2
N- (3-chloro-phenyl) -acetamido] -2 tert-butyl acetate, but starting from 6.8 g of (3-methylthio phenyl) 2-amino tert-butyl acetate, 3 g of triethylamine and 6 g of phthalimido-2 acetyl chloride. There was thus obtained after crystallization from diisopropyl ether, 7.6 g of [phthalimido-2 N- (3-methylthio-phenyl) -acetamido] -2 tert-butyl acetate melting at a temperature of 1410C.

 Tertiary butyl (3-methylthio phenyl) amino-2 acetate can be prepared in a similar manner to that described in Example 1 for the preparation of tert-butyl [3-chloro phenyl) amino-2 acetate, but from 8.4 g of 3-methylthio aniline and 5.9 g of tert-butyl bromoacetate. There was thus obtained 6.8 g of (3-methylthio phenyl) amino-2 tert-butyl acetate in the form of an oil used as it is in the subsequent syntheses.

EXAMPLE 15
By operating in a manner analogous to that described in Example 11, but starting from 3.4 g of [2-amino-N- (2-chloro-phenyl) -acetamido] -2 N-methyl N-phenyl- acetamide and 1.4 g of 3-methylphenyl isocyanate, 2.2 g of [[(3-methylphenyl) -3 ureido] -2 N- (2-chloro-phenyl) were obtained after recrystallization from acetonitrile ) -acetamido9-2 N-methyl
N-phenyl-acetamide melting at 1800 C.

[2-Amino N- (2-chloro phenyl) -acetamido [-2 N-methyl
N-phenyl acetamide can be prepared in a similar manner to that described in Example 4 for the preparation of [2-amino
N- (2-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate, but from 5.6 g of [phthalimido-2 N- (chlm2 phenyl) -acetamido] -2 N-methyl N-phenyl- acetamide and 1.9 g of hydrazine hydrate. 3.3 g of [2-amino
N- (2-chloro-phenyl) -acetamido] -2 N-methyl N-phenyl-acetamide in the form of an oil used as it is in subsequent syntheses.

[Phthalimido-2 N- (2-chloro-phenyl) -acetamido] - 2 N-methyl
N-phenyl-acetamide can be prepared in a similar manner to that described in Example 4 for the preparation of [phthalimi2
N- (2-trifluoromethoxyphenyl) -acetamido] -2 tert-butyl acetate, but starting from 7.4 g of phthalimido-2 N- (2-chloro-phenyl) acetamide, 1.3 g of a suspension oily (50% by weight) of sodium hydride and 5.9 g of braro-2 N-methyl N-phenyl acetamide. 5.7 g of [phthalimido-2 N- (2-chloro-phenyl) -acetamido] -2 are thus obtained, after recrystallization from ethyl acetate.
N-methyl N-phenyl-acetamide melting at 1680C.

 Phthalimido-2 N- (2-chloro-phenyl) -acetamide can be prepared in a manner analogous to that described in Example 4 for the preparation of phthalimido-2 N- (tri fluoranethoxy-2-phenyl) acetamide, but at from 3.8 g of chlorinated aniline, 3.3 g of triethylamine and 7.2 g of 2-phthalimido acetyl chloride. 7.5 g of phthalimido-2 N- (chlo2 phenyl) -acetamide are thus obtained, melting at 2500C.

 2-bromo-N-methyl N-phenyl-acetamide can be prepared by the method described by C.A. BISCHOFF, Chem. Ber., 34, 2125 (1901).

EXAMPLE 16
Frightening in a manner similar to that described in Example 11 but from 4.2 g of [2-amino-N- (2-methoxyphenyl) -acetamido] -2 tert-butyl acetate and 1 , 9 g of 3-methylphenyl isocyanate, after recrystallization from ethyl acetate, 3 g of rr (3-methylphenyl) -3 ureido] -2 N- (2-methoxyphenyl) -acetamido are obtained ] -2 tert-butyl acetate melting at 171 ° C.

[2-Amino-N- (2-methoxyphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [2-amino N- (chlorine3 phenyl) -acetamido] -2 tert-butyl acetate, but from 8.4 g of [phthalimido-2 N- (2-methoxyphenyl) -acetamido] -2 tert-butyl acetate, 3 g of hydrazine hydrate and operating at a temperature close to 200C. 4.2 g of amino-2 are thus obtained
N- (2-methoxyphenyl) -acetamido] -2 tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

[Phthalimido-2 N- (2-methoxyphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [phthalimido-2
N- (3-chloro-phenyl) -acetamido] -2 tert-butyl acetate, but from 6.4 g of r (2-methoxyphenyl) amino] -2 tert-butyl acetate, 2.7 g of triethylamine and 6 g of 2-phthalimido acetyl chloride. 8.4 g of [phthalimido-2 N- (2-methoxy-phenyl) acetamido] -2 tert-butyl acetate, melting at 1440C, are thus obtained after recrystallization from diisopropyl ether.

 Tertiary butyl (2-methoxyphenyl) amino-2 acetate can be prepared in a similar manner to that described in Example 1 for the preparation of tert-butyl acetate (3-chloro-phenylamino) -2, but from 7.4 g of 2-methoxy aniline and 5.9 g of tert-butyl bromoacetate. 6.4 g of (2-methoxyphenyl) 2-amino-tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

ExHMPI 17
At a suspension of 3.7 g of t (3-methylphenyl) -3 ureido] -2 acetic acid in 230 an3 of 1,2-dichloroethane, maintained under an argon atmosphere, a temperature close to 200C, 4.5 g of (4-nitro phenyl) 2-amino tert-butyl acetate. The reaction mixture is heated under agitation until the solvent refluxes. 2.12 g of sulfinyl chloride are then added dropwise, while maintaining the reflux. When the addition is complete, heating at reflux is continued for 10 minutes, then the reaction mixture is cooled to a temperature in the region of 100C and poured into a solution of 15 g of sodium hydrogen carbonate in 300 cm3 of distilled water. aqueous solution is separated by decantation and re-extracted with 2 times 50 cm3 of 1,2-dichloroethane.

The organic phases are combined, washed with 3 times 20 cm3 of distilled water, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The residue is purified by chromatography on 200 g of silica (0.063-0.2 mm) contained in a column 3.5 years in diameter, eluting cyclohexane-ethyl acetate (50-50 in voltines)], collecting fractions of 30 years 3. Fractions 16 to 25 are combined and calcined to dryness under reduced pressure (2.7 kPa) at 400C. after recrystallization from ethyl acetate, 2.9 g of [[(methyl-3 phenyl) -3 ureido] -2 N- (4-nitro-phenyl) -acetamido] -2 melting tert-butyl acetate are obtained at 1,520C.

 Tertiary butyl (4-nitro-phenyl) amino-2 acetate can be prepared as follows: a mixture of 6.9 g of nitre4 aniline, 19.5 g of tert-butyl bromoacetate and 9.24 g of sodium hydrogencarbonate is heated with stirring and under an argon atmosphere, at a temperature of 1600C, for 2 hours and 30 minutes then cooled to a temperature close to 200C and poured into ns a mixture of 150 cm of distilled water and 150 cm3 of ethyl acetate. The aqueous phase is separated by decantation and re-extracted with 3 times 50 cm of ethyl acetate. The organic phases are combined, washed with 3 times 20 cm of distilled water, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. After recrystallization from a mixture of ethyl acetate and cyclohexane (50-50 by volume), 7.7 g of tert-butyl acetate (4-nitrc-phenyl) -2-acetate melting at 1240C.

 Acetic [(3-methylphenyl) -3 ureido] -2 acetic acid can be prepared as follows: to a solution of 7.5 g of glycine and 8.4 g of sodium hydrogen carbonate in 250 cm3 d distilled water, at a temperature in the region of 200 ° C., 13.3 g of 3-methylphenyl isocyanate are added. The reaction mixture is stirred for 18 hours at a temperature in the region of 200C, then the insoluble product is separated by filtration and washed with 2 times with 30 cm of distilled water and then with 2 times 30 cm3 of ethyl acetate.

The filtrates are combined, the aqueous phase is separated by decantation and acidified with a 5N aqueous hydrochloric acid solution to a pH close to 1. The solid formed is separated by filtration, washed with 2 times 30 cm3 of water distilled then with 2 times 30 cm3 of ethyl acetate and air dried. 16.3 g of [(3-methyl-3-phenyl ureido] -2 acetic acid melting at 2250C are thus obtained.

EXAMPLE 18
By operating in a manner analogous to that described in Example 17 but starting with 1.04 g of r (3-methylphenyl) -3 ureido] -2 acetic acid, 1.4 g of (dichloro- 2,3 phenyl) 2-amino tert-butyl acetate and 0.6 g of sulfinyl chloride, after recrystallization from acetonitrile, 0.3 g of rr (3-methylphenyl) -3 ureido is obtained] - 2 N- (2,3-dichloro-3 phenyl) acetamido] -2 tert-butyl acetate melting at 1350C.

 (2,3-Dichloro-phenyl) 2-amino tert-butyl acetate can be prepared as follows: to a solution of 32.4 g of 2,3-dichloro-aniline in 100 cm of acetonitrile is added, to a temperature in the region of 200C, 16.8 g of sodium hydrogencarbonate, then a solution of 39 g of tert-butyl bromoacetate in 50 cm3 of acetonitrile. The reaction mixture is stirred at reflux for 48 hours then cooled to a temperature in the region of 200C.

The insoluble product is separated by filtration and washed with 50 cm of acetonitrile. The filtrates are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The residue is purified by chromatography on 300 g of silica (0.063-0.2 mm) contained in a column 4 years in diameter [eluent: cyclohexane-ethyl acetate (90-10 by volume)] by collecting fractions of 50 year 3. The fractions containing only the desired product are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 33 g of (2,3-dichloro-phenyl) 2-amino-tert-butyl acetate were thus obtained in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 19
By operating in a manner analogous to that described in Example 17, but starting from 3.12 g of ((3-methylphenyl) -3 ureido] -2 acetic acid, of 4.3 g of (brar2 phenyl) 2-amino tert-butyl acetate and 2 g of sulfinyl chloride, after recrystallization from a mixture of diisopropyl ether and acetonitrile (80-20 by volume), 0.6 g of ([ (3-methylphenyl) -3 ureido] -2 N- (2-bromo phenyl) -acetamido] -2 tert-butyl acetate melting at 1580C.

 2-bromo-phenyl) 2-amino tert-butyl acetate can be prepared in a manner analogous to that described in Example 18 for the preparation of 2,3-dichloro-phenylamino) -2 tert-butyl acetate, but from 34.4 g of 2-bromo aniline, 8.4 g of sodium hydrogencarbonate and 19.5 g of tert-butyl braroecetate. There was thus obtained 17.4 g of (2-bromo-phenyl) 2-amino tert-butyl acetate in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 20
By using a method analogous to that described in Example 17, but using 2.08 g of [(3-methylphenyl) -3 ureido] -2 acetic acid, 3.07 g of (trifluoromethylthio -3 phenyl) amino-2 tert-butyl acetate and 1.3 g of sulfinyl chloride, 0.8 g of [((3-methylphenyl) -3 ureido) were obtained after recrystallization from diisoprooyl oxide ] -2 N- (triflu ranethylthio-3 phenyl) -acetamido] -2 tert-butyl acetate melting at 1120C.

 Tert-butyl (3-trifluoromethylthio-phenyl) amino-2 acetate can be prepared in a manner analogous to that described in Example 18 for the preparation of tert- (2,3-dichloro phenyl) amino-acetate butyl, but from 19.3 g of trifluoromethylthio-3-aniline, 8.4 g of sodium hydrogencarbonate and 19.5 g of tert-butyl braoacetate. 25.5 g of (3-trifluoromethylthio-phenyl) 2-amino-tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 21
To a solution of 5.5 g of [phthalimido-2 N- (2-methylphenyl) -acetamido] -2 tert-butyl acetate in 90 cm3 of dichloromethane is added, at a temperature in the region of 0.13 g of methylhydrazine. The reaction mixture is stirred for 30 hours at a temperature in the region of 200C and then for 1 hour at reflux. After cooling, ai added 100 cm of distilled water, stirred and separated by decantation the aqueous phase which is reextracted with 2 times 60 om3 of dichloromethane. The organic phases are combined, washed with 2 times 15 cm of distilled water, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 400. This gives [2-amino - (2-methylphenyl) -acetamido] -2 tert-butyl acetate in the form of an oil which is dissolved in 40 cm of anhydrous tetrahydrofuran. 1.77 g of 3-methylphenyl isocyanate are added to this solution, then the reaction mixture is stirred for 1 hour at a temperature in the region of 200C and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 1.05 g of [[(3-methylphenyl) -3 ureido] -2 N- (2-methylphenyl) acetamido] -2 tert-butyl acetate, melting at 1330C, is obtained after recrystallization from petroleum ether .

[Phfalimido-2 N (2-methylphenyl) -acetamido-2 tert-butyl aoetate can be prepared in a manner analogous to that described in Example 1 for the preparation of [phthalimido-2
N- (3-chloro-phenyl) -acetamido] -2 tert-butyl acetate, but from 5.2 g of (2-methylphenyl) 2-amino-tert-butyl acetate, 2.6 g of triethylamine and 5.3 g of 2-phthalimidb-aoetyl chloride. There was thus obtained, after recrystallization from ethyl acetate, 5.5 g of [phthalimido-2 N- (2-methylphenyl) -acetamido] -2 tert-butyl acetate melting at 1400C.

 Tertiary butyl (2-methylphenyl) amino-2 acetate can be prepared in a manner analogous to that described in Example 18 for the preparation of tert-(2,3-dichloro phenyl) amino-acetate butyl but from 6.4 g of 2-methyl aniline, 2.5 g of sodium hydrogencarbonate and 5.85 g of tert-butyl bromoacetate. 5.2 g of (2-methylphenyl) amino-2-tert-butyl acetate were thus obtained in the form of an oil used in the subsequent syntheses.

EXAMPLE 22
The procedure is analogous to that described in Example 17 but starting with 1.8 g of tert-butyl N- (4-chloro-phenyl) glycinate, 1.56 g of [(3-methylphenyl) acid ) -3 ureido] -2 acetic acid and 0.89 g of thionyl chloride. The product obtained is purified by chranatography on 60 g of silica gel (0.04-0.063 mm) contained in a column 2.5 years in diameter [eluent: ethyl cyclohexaneacetate (80-20 by volume)] using a nitrogen overpressure of 40 kPa and collecting 20 year fractions3. Fractions 21 to 25 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. After crystallization from acetonitrile, 0.5 g of [N- (4-chloro-phenyl) ((3-methylphenyl) -3 ureido] -2 acetamido] -2 tert-butyl acetate, melting at 1250C, is obtained.

 T-butyl N- (4-chloro-phenyl) glycinate can be prepared as follows: to a solution of 12.7 g of 4-chloro aniline in 100 cm 3 of acetonitrile, 9.7 g of bromoacetate are added of tert-butyl and the mixture is stirred at reflux for 3 hours. The insoluble product is separated by filtration and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa) at 400 C. The product obtained is purified by chromatography on 150 g of silica gel (0.065-0.2 mm) contained in a column 2 cm in diameter [eluent: cyclohexane-ethyl acetate (70-30 by volume)], collecting 20 cm fractions. After concentration under reduced pressure (2.7 kPa) at 400C, 11.9 g of tert-butyl N- (4-chloro-phenyl) glycinate are obtained in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 23
The procedure is analogous to that described in Example 1 but starting with 2.3 g of [2-amino-N- (3-methoxyphenyl) acetamido] -2 tert-butyl acetate and, from 1 , 1 g of 3-methylphenyl isocyanate. The product obtained is purified by chromatography on 150 g of silica gel (0.04-0.063 mm) contained in a colone 3.5 years in diameter [eluent: cyclohexane-ethyl acetate (70-30 by volume)] using a 40 kPa nitrogen overpressure and collecting 20 cm fractions. Fractions 10 to 16 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. year, after recrystallization from diisopropyl ether, 2.2 g of (L (3-methylphenyl) -3 ureido] -2 N- (3-methoxyphenyl) -acetamido] -2 tert-butyl acetate fondant at around 60 C.

[2-Amino-N- (3-methoxyphenyl) -acetamido] -2 tert-butyl acetate can be prepared in a manner analogous to that
described in Example 1 for the preparation of [(amino-2
N- (3-chloro-phenyl) acetamido] -2 tert-butyl acetate, but at
from 3.4 g of tphthalimido-2N- (3-methoxyphenyl) acetamido] -2
tert-butyl acetate and 0.8 g of hydrazine hydrate. We
2.0 g of [2-amino-N- (3-methoxyphenyl) acetamido] -2
tert-butyl acetate in the form of an oil used as it is
in subsequent syntheses.

[Phthalimido-2 N- (3-methoxyphenyl) acetamido] -2 acetate
tert-butyl can be prepared as follows:
6.3 chloro-2 N- (3-methoxyphenyl) -acetamido] -2 solution
tert-butyl acetate in 100 cm3 of dimethylformamide, we add
7.5 g of phthalimide potassium. The mixture is stirred at a temperature
close to 1000C for 5 hours then poured into 1000 cm3 of water
distilled. The insoluble product is separated by filtration, washed with
3 times 60 cm3 of distilled water and air dried. we get after
recrystallization from diisopropyl ether, 6.7 g of [N- (me-
3-thoxyphenyl) 2-phthalimido acetamido] -2 tert-butyl acetate
melting at 1380C.

[2-Chloro-N- (3-methoxyphenyl) -acetamido] -2 acetate
tert-butyl can be prepared as follows: at a
7.9 g solution of (3-methoxyphenyl) 2-aminoacetate
tert-butyl and 6.7 g of triethylamine in 50 cm of
1,2-dichlorc ethane maintained at a temperature close to 150C, we
add 5.7 g of chloroacetyl chloride. The mixture is stirred
for 6 hours at a temperature close to 600C. After
cooling, it is washed with 3 times 100 cm3 of distilled water. The
organic phase is dried over magnesium sulfate and concentrated to
dry under reduced pressure (2.7 kPa) at 400C. we thus obtain, after
recrystallization from diisopropyl ether, 6.3 g of [chloro-2
N- (3-methoxy-methyl) -acetamido] -2 tert-butyl acetate melting at
1100C.

 Tert-butyl (3-methoxy-phenyl) amino-2 acetate can be prepared in a manner analogous to that described in Example 1 for the preparation of tert-butyl (3-chloro-phenyl) amino-acetate, but from 12.4 g of 4-methoxy aniline and 9.75 g of tert-butyl bromoacetate. The product obtained is purified by chromatography on 200 g of silioe gel (0.063-0.200 mm) supplied in a column of 7.0 years in diameter (eluent dichloroethane), collecting 60-year fractions. Fractions 10 to 20 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. 9.8 g of (3-methoxyphenyl) 2-aminc-tert-butyl acetate are thus obtained in the form of an oil used as it is in subsequent syntheses.

EXAMPLE 24
To a solution of 1.2 g of [N- (4-dimethylamino phenyl) [(imidazolyl-1) carboxamido] -2 acetamido] -2 tert-butyl acetate in 30 cm of toluene, ai added 0.83 g of 3-methylthio aniline and the mixture is stirred at reflux for 4 hours. After cooling, 30 cm of ethyl acetate are added, then the solution obtained is washed successively with 30 cm3 of distilled water, with 2 times 30 cm of a 1N aqueous solution of hydrochloric acid, with 2 times 30 cm3 of a saturated aqueous solution of sodium hydrogencarbonate and per 30 cm of a saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulphate then concentrated to dryness under reduced pressure (2.7 kPa) at 400 C. The residue is purified by chromatography on 100 g of silica gel (0.065-0.200 mm) contained in a column of 2 , 7 cm in diameter (eluent: methylene chloride), collecting 70 year fractions. Fractions 24 to 32 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. Obtained after recrystallization from acetonitrile.

0.40 g g of [N- (4-dimethylamino phenyl) [(3-methylthio phenyl) -3 ureido] -2 acetamido] -2 tert-butyl acetate melting at 1600C.

 [N- (4-dimethylaminc-phenyl) [(imidazolyl-1) cartoxamido] -2 acetamido] -2 tert-butyl acetate can be prepared as follows: to a solution of 0.58 g of N, N ' -diimidazole carbonyl in 20 cm of anhydrous tetrahydrofuran, a solution of 1.2 g of [2-amino-N- (4-dimethyllamino phenyl) acetamido] -2 tert-butyl acetate in 15 cm of anhydrous tetrahydrofuran is added. The solution is stirred for 3 hours at a temperature close to 200C, then concentrated to dryness under reduced pressure (2.7 kPa) at 400C. The residue is dissolved in 30 cm3 of ethyl acetate and the solution obtained is washed successively with 4 times 20 cm3 of distilled water and with 25 cm of a saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulphate then concentrated dry to dryness under reduced pressure (2.7 kPa) at 400C. After recrystallization from ethyl acetate, 1.2 g of [N- (dnmethylaminc-4 phenyl) E (imidazolyl-1) 2-carboxamido-acetamido] -2 tert-butyl acetate, melting at 1100C, is obtained.

EXAMPLE 25
To a solution of 1.1 g of [2-amino-N- (4-dimethylamino phenyl) -acetamido] -2 tert-butyl acetate in 35 cm3 of 1,2-dichlorc-ethane stirred at a temperature in the region of 250C, 0.55 g of triethylamine is added, then 0.9 g of indollecarbonyl-2 chloride dissolved in 35 cm3 of 1,2-dichlorc-ethane.

The reaction mixture is stirred for 18 hours at a temperature in the region of 250C. 250 cm3 of dichloromethane and then 125 cm3 of a saturated aqueous sodium hydrogencarbonate solution are then added. The organic phase is washed with twice 125 cm3 of distilled water, dried over magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa) at 400C. After recrystallization from ethyl acetate, 0.35 g of
N- [N-tert-butoxycarbonylmethyl) N- (4-dimethylamino phenyl) carbamoylmethyl] indolecarboxamide-2 melting at 230 C.

 Indolecarbonyl-2 chloride can be prepared as follows: to a suspension of 1.85 g of indolecarboxylic acid-2 in 40 om3 of anhydrous diethyl ether at a temperature in the region of 50C, an add 0.1 cm3 of dimethylformamide, then 1.5 g of oxalyl dichloride dissolved in 10 cm3 of anhydrous diethyl ether. The reaction mixture is stirred at a temperature in the region of 250C for 2 hours. The ethereal phase is centered to dryness under reduced pressure (2.7 pKa) at 30 C. This gives 1.8 g of indolecarbonyl-2 chloride, melting at 1200C.

 The present invention also relates to medicaments consisting of at least one compound of formula (I) in the pure state or in the form of an oaaosition in which it is associated with any other pharrrraceutically compatible product, which may be inert or hysiologically active. The medicaments according to the invention can be used by the oral, parenteral, rectal or topical route.

 apart from solid compositions for oral administration, tablets, pills, powders (gelatin capsules, cachets) or granules can be used. In these compositions, the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica. These compositions can also include substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a colorant, a coating (dragees) or a varnish.

 As liquid composites for oral administration, ai may use acceptable pharmaceutical solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin. These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.

 The sterile compositions for parenteral administration may preferably be aqueous solutions or non-aqueous solutions, suspensions or emulsions. As solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other suitable organic solvents can be used. . These compositions may also contain adjuvants, in particular wetting agents, sotonizing agents, emulsifiers, dispersants and stabilizers. Sterilization can be carried out with several baleen, for example by aseptic filtration, by adding to the composition of the sterilizing agents, by irradiation. or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in a sterile injectable medium.

 The compositions for rectal administration are suppositories or rectal capsules which contain, in addition to the active product, excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.

 The compositions for topical administration can be, for example, creams, ointments, lotions, eye drops, mouthwashes, nasal drops or aerosols.

 In human therapy, the compounds according to the invention are particularly useful in the treatment and prevention of disorders linked to oeK in the nervous system and the gastrointestinal tract. These components can therefore be used in the treatment and prevention of psychoses, anxiety disorders, Parkinson's disease, tardive diskinesia, irritable bowel syndrome, acute pancreatitis, ulcers, intestinal motility disorders. , certain tumors of the lower esophagus, colon and intestine, and as a potentiator of the analgesic activity of narcotic and non-narcotic analgesic drugs and carmine regulator of appetite.

 The doses depend on the desired effect, the duration of the treatment and the route of administration used; they are generally between 0.05 g and 1 g per day orally for an adult with unit doses ranging from 10 mg to 500 mg of active substance.

 Generally, the attending physician will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.

The following examples illustrate the compositions according to the invention
EXAMPLE A
Using the usual technique, capsules containing 50 mg of product having the following composition are prepared
- [(3-methylphenyl) -3 ureido] -2 N- (2-chloro
phenyl) -acetamido] -2 tert-butyl acetate .... 50 mg
- cellulose ...................................... 18 mg
- lactose. .... 55 mg
- colloidal silica ................ .... 1 mg
- sodium carboxymethyl starch ...... .... 10 mg
- talc ................................. 10 mg
- magnesium stearate. .... 1 mg
EXAMPLE B
Is prepared, according to the usual technique, ocoprimés dosed with 50 mg of active product having the following osmposition
- ((3-methylphenyl) -3 ureido] -2 N- (2-ethoxycarbonyl
phenyl) -acetamido] -2 tert-butyl acetate .... 50 mg
- lactose ................................... 104 mg
cellulose. . 40 mg
- polyvidone .. .. 10 mg
- sodium carboxymethyl starch ...... .... 22 mg
- talc ................................ 10 mg
- magnesium stearate. .. 2 mg
- oolloidal silioe .............................. 2 mg
- mixture of hydroxymethylcellulose, glycerin, oxide of
titanium (72-3,5-24,5) gsp

1 film-coated tablet finished at 245 mg
EXAMPLE C
preparing a solution for injection containing 10 mg of active product having the following composition - t [(3-methylphenyl) -3 ureido] -2 N- (4-methoxy
ph'enyl) -acetamido] -2 tert-butyl acetate 10 mg - benzoic acid ............................... 80 mg - benzyl alcohol .............................. 0.06 cm3 - sodium benzoate ....... ........... .......... 80 mg - 95% ethanol 0.4 cm3 - sodium hydroxide .............. ............. 24 mg - propylene glycol .............................. 1, 6 cm - water ................................ qs 4 cm3

Claims (10)

 in which - R1 represents a hydrogen atom, an alkyl, alkoxycarbonyl or phenyl radical optionally substituted by one or more substituents chosen from halogen atoms and the allyl, alkoxy, alkylthio, nitro and amino radicals.

 CLAIMS 1. Compounds of formula R2 represents an alkoxy, cycloalkyloxy radical (optionally substituted by at least one alkyl radical), cycloalkylalkyloxy, phenylalkyloxy, polyfluoroalkyloxy, cinnamyloxy, a chain -NR5R6 in which R5 and R6 are identical or different represent a hydrogen atom, an alkyl radical, phenyl (optionally substituted by one or more substituents chosen from halogen atoms and allyl, alkoxy, alkylthio radicals), indanyl, cycloalkylalkyl, cycloalkyl, phenylalkyl or else R5 and R6 form together with the nitrogen atom to which they are attached a heterocycle, - R3 represents a phenylamino radical (the phenyl nucleus of which is optionally substituted by one or more substituents chosen from halogen atanes and the alkyl, alkoxy and alkylthio radicals), phenyl (optionally substituted by one or more chosen substituents among the halogen atoms and the alkyl, alkoxy and alkylthio), naphthyl, indolyl or q radicals uinolyl, - R4 represents a phenyl radical substituted by one or more substituents chosen from halogen atanes, alkyl, alkoxy, dialkylamino, nitro, alkylthio, alkoxycarbanyl, acylamino, trifluoromethoxy, methylenedioxy, trifluoromethyl, trifluoromethylthio, phenoxy, phenoxy benzyl, it being understood that the alkyl and alkoxy radicals and the alkyl, alkoxy and acyl portions contain 1 to 4 carbon atanes in a straight or branched chain and that the cyclo alkyl radicals and portions contain 3 to 6 carbon atanes, as well as their racemates and their enantiomers when they contain one or more asymmetric centers.  2. Compounds of formula (I) according to claim 1 for which R5 and R6 form, together with the nitrogen atom to which they are attached, a piperidino ring optionally substituted by at least one alkyl radical, a perhydroazepinyl-1, indolinyl ring, tetrahydro-1,2,3,6 pyridyl-1, tetrahydro-1,2,3,4 quinolyl-11, pyrrolidinyl, 4H dihydro2,3 benzoxazine-1,4, 4H dihydro-2,3 benzothiazine-1,4 or N-alkyl tétrahydro-1,2,3,4 quinoea'ine-1.  3. Compounds of formula (I) according to claims 1 and 2 in which the halogen atanes are chlorine, bromine and fluorine atones.  4. Method for preparing the compounds of formula (I) according to claim 1 for which R3 represents a phenylamino radical in which the phenyl nucleus is optionally substituted by one or more substituents chosen from halogen atanes and alkyl, alkoxy and alkylthio radicals characterized in that an isocyanate of formula is reacted  OCN-R7 (11) in which R7 represents a phenyl radical optionally substituted by one or more substituents chosen from halogen atanes and alkyl, alkoxy and alkylthio radicals, on an amino derivative of formula

 in which R1,  R2 and R4 have the same meanings as in claim 1, then isolate the product.  5. Process for preparing the compounds of formula (I) according to claim 1 for which R3 represents a phenylamino radical in which the phenyl nucleus is optionally substituted, characterized in that an amine of formula is reacted  R4-NH-CH (R1) -CO-R2 (VI) in which R1, R2 and R4 have the same meanings as in claim 1, on an acid of formula  HOOC-CH2-NH-CO-R3 (XVI) in which R3 has the same meanings as in claim 1 or a reactive derivative of this acid, then isolates the product.  6. Process for preparing the compounds of formula (I) according to claim 1 for which R3 represents a phenylamino radical in which the phenyl nucleus is optionally substituted, characterized in that a derivative of formula is reacted

 in which R1, R2 and R4 have the same meanings as in claim 1, on an amine of formula  H2N-Rg (xx) in which Rg represents a phenyl radical optionally substituted by one or more substituents chosen from halogen atanes and allyl, alkoxy and alkylthio radicals and then isolates the product.  7. Process for the preparation of the compounds of formula (I) according to claim 1 for which R3 represents an optionally substituted phenyl, naphthyl, indolyl or quinolyl radical, characterized in that an amine of formula is reacted

 in which R1, R2 and R4 have the same meanings as in claim 1 on a derivative of formula  HOOC-R3 (xX) in which R3 has the same meanings as above and then isolates the product.  8. Medicines characterized in that they contain as active ingredient at least one compound of formula (I) according to claim 1.  9. Medicines characterized in that they contain as active ingredient at least one compound according to claim 2.  10. Medicines according to claims 8 and 9 for the treatment or prevention of disorders related to CCK in the nervous system and the gastrointestinal system.