FR2458547A2 - Antidepressant aryl derivs of azolone(s) - prepd. e.g. from hydroxymethyl-nitrobenzyl-oxy:phenyl oxazolidine thione - Google Patents

Abstract

N-Aryl azolones of formula (I) are new. X is S; A is O; R1 is H; R2 is -CH2-O2C-Et and R is (II); or R2 is -CH2OH and R is (III) NC-CH2-CH2-CH2O or NC-CH2-CH2CH2CH2O; or R2 is MeO-CH2- and R is (IV),(V) CH3-CHMe-CH2CH2O-, (VI) or NC-CH2CH2CH2CH2O-; or R2 is EtO-CH2- or CH3-CH2CH2OCH2 and (VII) in an alternative, X is O; A is S; R1 is H; R2 is MeO-CH2-; and R is (VIII). (I) are antidepressant agents. The cpds. are prepd. by various conventional methods depending on the value of individual substituents.

Description

présentant des activités intéressantes dans le domaine psychotrope comme antidépresseurs potentiels.The main patent application No. 78 17388 relates to N-aryl oxazolidinones, oxazolidinethiones and pyrrolidinones of general formula:

presenting interesting activities in the psychotropic field as potential antidepressants.

dans laquelle l'ensemble (X, A, R1) prend l'une quelconque des valeurs suivantes
a) (S, O, }{),auquel cas R2 représente
- soit un groupe ester de formule -CH2-OCOEt et R désigne alors
le groupe métanitrobenzyloxy,
- soit le groupe hydroxyméthyle et R désigne alors le groupe
(cyano-3 fluoro-8) benzyloxy, (cyano-3) propoxy ou (eyano-4)
butoxy,
- soit le groupe méthoxyméthyle et R représente alors le groupe
(cyano-3 nitro-5) benzyloxy, (pyridyl-3) méthyloxy, (méthyl-3)
butoxy, cyclopentylméthyloxy ou (cyano-4) butoxy,
- soit un groupe éthoxyméthyle ou n-propoxyméthyle et R désigne
alors le groupe métanitrobenzyloxy ;
b) (O, S, H), auquel cas R2 représente le groupe méthoxyméthyle et
R désigne alors le groupe métanitrobenzyloxy
c) (H2, CH2, H), auquel cas R2 représente le groupe hydroxyméthyle
et R désigne alors le groupe benzyloxy
d) (O, O, H), auquel cas R2 représente
- soit un groupe ester de formule -CH2-OCO-CH2-O-C H et R
désigne alors le groupe métanitrobenzyloxy, - soit un groupe ester de formule -CH2-OCO-C4H9(t) et R désigne
alors le groupe para aminobenzyloxy ou para formylaminobenzy
loxy, - soit un groupe méthoxyméthyle et R représente alors
le groupe dim6thylamino, un groupe phényle substitué ou non de formule

dans laquelle R3 = H,3-Cl, 4-Cl, 3-NO2 ou 3-CN, le groupe benzyle, un groupe styryle de configuration trans, de formule

dans laquelle R4 = H,Cl, NH2, CN ou N02, le groupe styryle ou métanitrostyryle, de configuration cis, un enchaînement bcétylènique de formule

dans laquelle R5 = = ,2-Cl, 3-Cl, 4-C1, 3-NO2 ou 3-CN, l'enchaînement (méthyl-4 pentyne-1)yl-1

ou (cyclohexyl-2 éthyne-1)yl-1

The present application for a second certificate of addition concerns new compounds having exactly the same basic structure and the same therapeutic activities. More precisely, these new compounds correspond to the general formula

in which the set (X, A, R1) takes any one of the following values
a) (S, O,} {), in which case R2 represents
or an ester group of formula -CH2-OCOEt and R denotes
the metanitrobenzyloxy group,
- the hydroxymethyl group and R then designates the group
(3-cyano-8-fluoro) benzyloxy, (3-cyano) propoxy or (4-cyano)
butoxy,
- the methoxymethyl group and R then represents the group
(3-cyano-5-nitro) benzyloxy, (3-pyridyl) methyloxy, (3-methyl)
butoxy, cyclopentylmethyloxy or (cyano-4) butoxy,
- an ethoxymethyl or n-propoxymethyl group and R denotes
then the metanitrobenzyloxy group;
b) (O, S, H), in which case R2 represents the methoxymethyl group and
R then designates the metanitrobenzyloxy group
c) (H2, CH2, H), in which case R2 represents the hydroxymethyl group
and R then denotes the benzyloxy group
d) (O, O, H), in which case R2 represents
or an ester group of formula -CH2-OCO-CH2-OC H and R
then denotes the metanitrobenzyloxy group, - an ester group of formula -CH2-OCO-C4H9 (t) and R denotes
then the para aminobenzyloxy or para formylaminobenzy group
loxy, - is a methoxymethyl group and R then represents
dimethylamino group, a substituted or unsubstituted phenyl group of formula

in which R 3 = H, 3-Cl, 4-Cl, 3-NO 2 or 3-CN, the benzyl group, a styryl group of trans configuration, of formula

in which R4 = H, Cl, NH2, CN or NO2, the styryl or metanitrostyryl group, of cis configuration, a betylenic chain of formula

wherein R5 = =, 2-Cl, 3-Cl, 4-Cl, 3-NO2 or 3-CN, the chain (methyl-4-pentyne-1) yl-1

or (2-cyclohexylethyl-1) yl-1

un groupe phénétyle de formule

dans laquelle R6 = H, Cl, N02 ou CN, un groupe benzoylméthyle de formule

dans laquelle R7 = Cl, N02 ou CN, un groupe phénoxyméthyle de formule

dans laquelle R7 a les mêmes significations que précédemment, un groupe benzyloxy de formule

dans laquelle
R8 = 3-Br, 3-I, 3-SCF3, 3-CN [énantiomère de configuration absolue R (-) , 3-CN [énantiomère de configuration absolue 3-CN (forme nacémique), 4-NH2, 4-NHCOCH3, 4-NHSO2CH3 4-N(CH3)-COCH3 ou 4-NH CH O, l'enhaînement (pyridaziryl-2) méthyloxy

ou (pyridinyl-3) méthyloxy

l'enchaînement (butène-2) oxy = CH-CH3 -O-) (méthyl-3 butène-2) oxy

(cyclopentèns-1yl1)méthyloxy

; cyclobutylméthyloxy ; (méthyl1 cyclopentyl-1) méthyloxy

morpholino-2

; (tétrahydropyranyl-3) méthyloxy chloro-4 butoxy ; (cyclohexanone 4-yl) méthyloxy

butoxy-4 one-2 (CH3 CO-(CH2)2-O-); pentoxy-5 one-2 (CH3 CO-(CH2)3-O-) ou l'oxime du propoxy-3 one-2

un enchaînement phénétyloxy de formule

dans laquelle R7 a les mêmes significations que precêdem- ment, le groupe métanitrodideutérobenzyloxy

ou le groupe méthyl-4(n)-pentyle, - soit un groupe N-éthylaminométhyle, N-isopropylaminométhyle,
pyrrolidinométhyle ou morpholinométhyleetRdésigne alors le
groupe métanitrobenzyloxy, - soit un groupe aminométhyle ou N,N-diméthylaminométhyle, et
R désigne alors le groupe métacyanobenzyloxy, - soit un groupe aminométhyle, et R désigne alors le groupe
(chloro-3 nitro-5) benzyloxy, - soit un groupe acétyle, et R désigne alors le groupe métani
trobenzyloxy, - soit un groupe hydroxy-l méthyle, et R représente alors le
groupe benzyloxy, métacyanobenzyloxy ou métanitrobenzyloxy,
les composés de formule (I) correspondants étant soit sous la
forme d'un mélange de quatre énantiomères, soit sous la forme
d'un couple de diastéréoisomères érythro (E) et d'un couple
de diastéréoisomères thrD(T), couples isolés par séparation
dudit mélange par chromatographie liquide à haute performance,
les dérivés érythro correspondant aux produits les moins
polaires, - soit un groupe méthoxy-l éthyle et R désigne alors un groupe
métanitrobenzyloxy, métacyanobenzyloxy ou benzyloxy, les
composés de formule (I) correspondants étant soit sous la
forme d'un mélange de quatre énantiomères, soit sous la forme
d'uncoupled diasteréoisomères érythro (E) et d'un couple de
diastéréoisomères thréo (T), couples isolés par séparation
liquide
dudit mélange par chromatographie/a haute performanee, les
dérivés érythro étant les moins polaires, - soit un groupe diméthoxy-l,l méthyle et R désigne alors un
groupe métacyanobenzyloxy, métanitrobenzyloxy, n-butoxy,
cyclopentylmethyloxy ou (cyano-2)éthoxy, - soit un groupe diéthoxy-l, l méthyle et R désigne alors le
groupe métachlorobenzyloxy, - soit un groupe dioxolanne-1,3 yl-2 et R désigne alors le
groupe métanitrobenzyloxy.

a phenethyl group of formula

in which R 6 = H, Cl, NO 2 or CN, a benzoylmethyl group of formula

wherein R7 = Cl, NO2 or CN, a phenoxymethyl group of formula

in which R7 has the same meanings as above, a benzyloxy group of formula

in which
R8 = 3-Br, 3-I, 3-SCF3, 3-CN [R (-) absolute configuration enantiomer, 3-CN [3-CN absolute configuration enantiomer (nacemic form), 4-NH2, 4-NHCOCH3 , 4-NHSO2CH3 4-N (CH3) -COCH3 or 4-NH CH O, the (2-pyridaziryl) methyloxy sequence

or (pyridinyl-3) methyloxy

the sequence (butene-2) oxy = CH-CH3 -O-) (3-methyl-2-butene) oxy

(Cyclopentèns-1yl1) methyloxy

; cyclobutylmethyloxy; (methyl1 cyclopentyl-1) methyloxy

morpholino-2

; (tetrahydropyranyl-3) methyloxy-4-chlorobutoxy; (cyclohexanone 4-yl) methyloxy

butoxy-4-one-2 (CH3 CO- (CH2) 2-O-); pentoxy-5-one-2 (CH3 CO- (CH2) 3-O-) or propoxy-3-one oxime 2

a phenethyloxy sequence of formula

in which R7 has the same meanings as above, the metanitrodideuterobenzyloxy group

or the methyl-4 (n) -pentyl group, - is an N-ethylaminomethyl, N-isopropylaminomethyl group,
pyrrolidinomethyl or morpholinomethyl and R then designates the
metanitrobenzyloxy group, either an aminomethyl or N, N-dimethylaminomethyl group, and
R then designates the metacyanobenzyloxy group, - an aminomethyl group, and R then designates the group
(3-chloro-5-nitro) benzyloxy, - or an acetyl group, and R then denotes the methanol group
trobenzyloxy, or a 1-hydroxy-methyl group, and R is then the
benzyloxy, metacyanobenzyloxy or metanitrobenzyloxy group,
the corresponding compounds of formula (I) being either under the
form of a mixture of four enantiomers, either in the form
of a couple of diastereoisomers erythro (E) and a couple
of diastereoisomers thrD (T), isolated pairs by separation
said mixture by high performance liquid chromatography,
erythro derivatives corresponding to the least
polar, - is a methoxy-1 ethyl group and R then designates a group
metanitrobenzyloxy, metacyanobenzyloxy or benzyloxy, the
corresponding compounds of formula (I) being either under the
form of a mixture of four enantiomers, either in the form
of uncoupled diastereoisomers erythro (E) and a couple of
threo (T) diastereoisomers, isolated pairs by separation
liquid
of said mixture by chromatography / high performance, the
erythro derivatives being the least polar, - a dimethoxy-l, 1 methyl group and R then designates a
metacyanobenzyloxy, metanitrobenzyloxy, n-butoxy group,
cyclopentylmethyloxy or (2-cyano) ethoxy, - is a diethoxy-l, 1 methyl group and R then designates the
metachlorobenzyloxy group, or a dioxolane-1,3 yl-2 group and R then designates the
metanitrobenzyloxy group.

dans laquelle X représente un atome de soufre ou d'oxygène, avec le chlorure de l'acide propionique ou phénoxyacétique, de préférence en milieu pyridinique ou en solution dans le T.H.F ou le chloroforme en présence de triéthylamine. Les composés de formule (II) sont synthétisés conformément au protocole décrit dans la demande de brevet français publiée sous le numéro 2 428 032.A) Compounds of formula (I) for which the set (X, A, R1) has the value (S, O, H), R2 then representing the group -CH 2 COEt, or (O, O, H), R2 then representing the group -CH2-OCO-CH2-OC H, are obtained by condensation of the compound of formula

in which X represents a sulfur or oxygen atom, with propionic acid or phenoxyacetic acid chloride, preferably in a pyridine medium or in solution in THF or chloroform in the presence of triethylamine. The compounds of formula (II) are synthesized according to the protocol described in the French patent application published under the number 2,428,032.

dans laquelle le couple (R', Rg) prend l'une quelconque des valeurs

B) The compounds (I) for which the group (X, A, R1) has the value (S, O, H) and R2 represents the hydroxymethyl, methoxymethyl, ethoxymethyl or n-propyloxymethyl group, are obtained by cyclization with thiophosgene compounds of formula

in which the pair (R ', Rg) takes any of the values

dans laquelle R à les mêmes sianifications que dans la formule (III), soit avec ltépoxy-2,3 propanol-1 quand R = CN-(CH) R-O, CN-(CH2)4-O ou

soit avec une chlorhydrine de formule

dans laquelle R9 a les mêmes significations que dans la formule (III).
C) Le composé de formule (I) pour lequel l'ensemble (x, A, R1, R2,
R) prend la valeur (O, S, H, CH20CH3

est obtenu par cyclisation par le phosgène du composé de formule

obtenu par condensation de la para (métanitrobenzyloxy) aniline avec le méthoxyméthyl-2 thiooxirane.The compounds of formula (III) are obtained by condensation of aniline of formula

wherein R at the same sianifications as in formula (III), or with 2,3-epoxypropanol-1 when R = CN- (CH) RO, CN- (CH 2) 4 -O or

with a chlorohydrin of formula

wherein R9 has the same meanings as in formula (III).
C) The compound of formula (I) for which the group (x, A, R1, R2,
R) takes the value (O, S, H, CH20CH3

is obtained by phosgene cyclization of the compound of formula

obtained by condensation of para (metanitrobenzyloxy) aniline with methoxymethyl-2 thiooxirane.

est obtenu par réduction de préférence par l'hydrure double de lithium et d'aluminium et en milieu
T.H.F, du composé de formule

ce dernier étant obtenu par estérification du composé de formule

lui-meme est obtenu par cyclisation de la parabenzyloxyaniline avec l'acide itaconique.D) The compound of formula (I) for which the group (X, A, R1, Rp,
R) takes the value (H2, CH2, H, CH20H,

is obtained by reduction preferably with the lithium aluminum hydride and in the medium
THF, of the compound of formula

the latter being obtained by esterification of the compound of formula

it itself is obtained by cyclization of parabenzyloxyaniline with itaconic acid.

et en traitant éventuellement le composé ainsi obtenu de formule

par le formiate d'éthyle.E) The compounds of formula (I) for which the group (X, A, R1,
R2) takes the value (O, O, H, CH20COChHgt) are obtained by reduction by amalgam mercuric chloride-aluminum of the compound of formula

and optionally treating the thus-obtained compound of formula

by ethyl formate.

obtenu comme décrit dans le brevet belge n 851 893.The compound of formula (IX) is obtained, for its part, by the action of pivaloyl chloride, preferably in pyridine or in THF in the presence of triethylamine, on the compound of formula

obtained as described in Belgian Patent No. 851 893.

dans lequel R3 a les mêmes significations que precedemment, un groupe benzyle, un groupe styryle trans de structure

F) The compounds of formula (I) for which the group (X, A, R1,
R2) takes the value (0, 0, H, CH2OCH3), R then designating a phenyl group of structure

in which R3 has the same meanings as before, a benzyl group, a trans-styryl group of structure

où R'7 = Cl ou CN, sont obtenus * soit par cyclisation par la potasse éthanolique ou le méthylate de sodium du composé de formule

dans laquelle R" prend les valeurs particulières de R énumérées ci-dessus.R'4 = H, Cl, NO2 or CN, a cis-styryl group or methanoltrotrophyl (cis) a benzoylmethyl group of structure

where R'7 = Cl or CN, are obtained either by cyclization with ethanolic potassium hydroxide or sodium methoxide of the compound of formula

wherein R "takes the particular values of R listed above.

dans laquelle R" a les mêmes valeurs que dans la formule(XI).The compounds of formula (XI) are obtained by the action of phosgene on 1-chloro-3-methoxypropanol-2, then by reaction of the intermediate compound thus prepared with an aniline of formula

in which R "has the same values as in formula (XI).

dans laquelle R3 = H, 3-Cl, 4-Cl ou 3-CN, sont obtenues par réduction de préférence par le fer en présence de chlorure d'ammonium et en milieu éthanolique, des dérivés nitrés correspondants.The compounds of formula (IVa) for which R "represents a phenyl group of structure

in which R 3 = H, 3-Cl, 4-Cl or 3-CN, are obtained by reduction preferably with iron in the presence of ammonium chloride and in ethanol medium, corresponding nitro derivatives.

The compound of formula (IVa) wherein R "means the metanitrophenyl group is obtained by a Beckmann reaction, using phosphorus pentachloride, on the oxime of para (metanitrophenyl) acetophenone.

(trans) où R'4 a les mêmes significations que ci-dessus sont obtenus par chromatographie liquide à haute performance (H.P.L.C.) des produits brute issue de l'hydrolyse acide des acétanilides de formule

dans laquelle R10 = H, Cl, N02 ou CNt
Les composés de formule (XII) sont obtenus par condensation du para acétamidobenzaldéhyde avec le composé de formule

dans laquelle R10 a la même signification que dans la formule (XII). Compounds of formula (IVa) for which R "represents a styryl (cis), metanitrostyryl (cis) group or a structural group

(trans) where R'4 has the same meanings as above are obtained by high performance liquid chromatography (HPLC) of the crude products resulting from the acid hydrolysis of acetanilides of formula

in which R10 = H, Cl, N02 or CNt
The compounds of formula (XII) are obtained by condensation of paraacetamidobenzaldehyde with the compound of formula

wherein R10 has the same meaning as in formula (XII).

dans laquelle R10 à les memes valeurs que dans la formule (XIII), avec la triphénylphosphine.The compounds of formula (XIII), for their part, are obtained by condensation of the derivatives of formula

wherein R10 at the same values as in formula (XIII), with triphenylphosphine.

dans laquelle P'7 = Cl ou CN, sont préparés par réduction par le fer, en présence de chlorure d'ammonium, en milieu éthanolique du composé nitré de formule

dans laquelle R7 a les mêmes significations que précédemment, les composés de formule (XV) étant obtenus par condensation du paranitrobenzaldéhyde, en présence de potasse méthanolique, avec le composé de formule

dans laquelle R' a les mêmes significations que dans la formule (XV). The compounds of formula (IVa) for which R "represents a benzoylmethyl group of structure

in which P'7 = Cl or CN, are prepared by reduction with iron, in the presence of ammonium chloride, in an ethanolic medium of the nitrated compound of formula

in which R7 has the same meanings as above, the compounds of formula (XV) being obtained by condensation of paranitrobenzaldehyde, in the presence of methanolic potassium hydroxide, with the compound of formula

wherein R 'has the same meanings as in formula (XV).

dans laquelle R'7 a les mêmes significations que dans la formule (XVI);
* soit par cyclisation de préférence par le méthylate de sodium
en solution toluènique, du composé de formule :

dans laquelle R" a les mêmes significations que dans la formule (XI). 7
The compounds of formula (XVI), for their part, are obtained by condensation of diphenylphosphite with the Schiff base of formula

wherein R'7 has the same meanings as in formula (XVI);
* either by cyclization, preferably with sodium methoxide
in toluene solution, of the compound of formula:

in which R "has the same meanings as in formula (XI).

où R" a les mêmes significations que dans la formule (IIIa), les composés de formule (IIIb) étant eux-mêmes obtenus par condensation du composé de formule (IVa) avec le ehloro-1 méthoxy-3 propanol-2.The compounds of formula (IIIa) are obtained by the action of ethyl chloroformate dissolved in dichloroethane on the compound of formula

where R "has the same meanings as in formula (IIIa), the compounds of formula (IIIb) being themselves obtained by condensation of the compound of formula (IVa) with 1-chloro-3-methoxypropanol-2.

est obtenu par réduction de préférence par le fer en présence de chlorure d'ammonium et en milieu éthanolique, du composé de formule (I) dans laquelle (X,A,R1,R2) = (O,O,H,CH20CH3) et R représente le groupe métanitrostyryle trans.G) The compound of formula (I) for which the group (XARRR) has the meaning (O, O, H, CH 2 OCH 3)

is obtained by reduction preferably with iron in the presence of ammonium chloride and in an ethanolic medium, of the compound of formula (I) in which (X, A, R 1, R 2) = (O, O, H, CH 2 OCH 3) and R represents the trans metanitrostyryl group.

est obtenu par condensation du composé de formule

avec le composé de formule

le composé de formule (XVIa) étant obtenu par condensation de la base de
Schiff de formule

avec le diphénylphosphite et le composé de formule (XVIII) étant obtenu par hydrolyse acide du composé de formule

H) The compound of formula (I) for which the group (X, A, R1, R2, R) has the value (O, O, H, CH20CH3,

is obtained by condensation of the compound of formula

with the compound of formula

the compound of formula (XVIa) being obtained by condensation of the base of
Schiff of formula

with diphenylphosphite and the compound of formula (XVIII) being obtained by acid hydrolysis of the compound of formula

lui-meme obtenu conformément au procédé décrit précédemment pour la synthèse se des composés de formule (XI). The latter is obtained by cyclization with methanolic potassium hydroxide or sodium methoxide, of the compound of formula

itself obtained in accordance with the process described above for the synthesis of compounds of formula (XI).

où R5 = H,2-Cl, 3-Cl, 4-Cl, 3-NO2 ou 3-CN, soit le groupe (méthyl-4 pentyne-1)yl-1 ou (cyclohexyl-2 éthyne-1)yl-1, sont obtenus par condensation des acétylures de cuivre de formules ::

où R5 a les mêmes significations que ci-dessus, avec le composé de formule

I) The compounds of formula (I) for which the group (X, A, R1, R2) has the value (O, O, H, CH 2 OCH 2) and R denotes either a phenylethynyl group of formula

where R5 = H, 2-Cl, 3-Cl, 4-Cl, 3-NO2 or 3-CN, either the (4-methyl-1-pentyne-1) yl-1 or (2-cyclohexyl-1-ethyne) group; 1, are obtained by condensation of copper acetylides of formulas ::

where R5 has the same meanings as above, with the compound of formula

selon le procédé décrit dans Angew. Chem. Inter. Edit. 9, 464, (1970).The compounds of formula (XX), (XXa) and (XXb) are obtained by the action of copper sulphate, in an ethanolic medium, in the presence of ammonia and of hydroxylamine hydrochloride on the true acetylenic derivatives corresponding to the compounds of formulas ( XX), (XXa) and (XXb), true acetylenic derivatives resulting from the action of selenium oxide on semicarbazones of formulas:

according to the method described in Angew. Chem. Inter. Edit. 9, 464, (1970).

obtenu à partir de la paraiodoaniline, selon le procédé déjà décrit pour la synthèse des composés de formules (XI) et (XIa). The compound of formula (XXI) is for its part obtained by cyclization with ethanolic potassium hydroxide or sodium methoxide, of the compound of formula

obtained from paraiodoaniline, according to the method already described for the synthesis of the compounds of formulas (XI) and (XIa).

dans laquelle R6 = H, Cl, NO2 ou CN, sont obtenus par réduction de référence par le triéthylsilane (SiEt3H) en présence d'acide trifluo roacétique, du composé de formule (I) pour lequel l'ensemble (X, A, R1, R2) prend la valeur (O, O, H, CH-
OCH3) et R désigne le groupe benzoylméthyle de structure

dans laquelle R6 a la meme signification que ci-dessus, la synthèse de ces composés particuliers de formule (I) étant effectuée selon les procédés décrits aux paragraphes F) et H) précédents. J) Compounds of formula (I) for which the group (X, A, R1, R2) has the value (O, O, H, CH2 OCH3) and R denotes a pyhénétyle group of formula

in which R6 = H, Cl, NO2 or CN, are obtained by reference reduction with triethylsilane (SiEt3H) in the presence of trifluoroacetic acid, with the compound of formula (I) for which the combination (X, A, R1 , R2) takes the value (O, O, H, CH-
OCH3) and R denotes the structure benzoylmethyl group

wherein R6 has the same meaning as above, the synthesis of these particular compounds of formula (I) being carried out according to the methods described in paragraphs F) and H) above.

dans laquelle R7 = Cl, N02 ou CN, sont obtenus par condensation du compose de formule

avec le métachloro-, métacyano-ou métanitrophénol, de préférence en milieu
T.H.F. et en présence d'azobisdicarboxylate d'éthyle(EtOCO-N=N-COOEt) et de triphénylphosphine.K) The compounds of formula (I) for which the group (X, A, R1, R2) has the value (O, O, H, CH2 OCH) and R denotes a phenoxymethyl group of structure

in which R7 = Cl, NO2 or CN, are obtained by condensation of the compound of formula

with metachloro-, metacyano- or metanitrophenol, preferably in medium
THF and in the presence of ethyl azobisdicarboxylate (EtOCO-N = N-COOEt) and triphenylphosphine.

formule

résultant de la condensation de la para [(tétrahydropyranyl-2) oxyméthyl] aniline avec le ehloro-1 méthoxy-3 propanol-2, selon les protocoles opératoires décrits dans la demande de brevet français n 2.428.032. The compound of formula (xxiii) is obtained either by reduction, preferably with sodium borohydride, the compound of formula (XVIII), or by acid hydrolysis of the compound of formula

formula

resulting from the condensation of para [(tetrahydropyranyl-2) oxymethyl] aniline with 1-chloro-3-methoxypropanol-2, according to the operating procedures described in French Patent Application No. 2,428,032.

-CH20- dans laquelle R7 = Cl, N02 ou CN, sont obtenus comme édemment, c'est-à-dire par condensation en milieu T.H.F., en présence d'azobisdicarboxylate d'éthyle et de triphénylphosphine, du phénétylalcool de formule

dans laquelle R7 a les mêmes significations que précédemment, avec le composé de formule

décrit dans le brevet belge nO 876;831. Compounds of formula (I) for which the set (X, A, R1, R2) has the value (O, O, H,
CH20CH3) and R denotes a phenethyloxy group of structure

In which R 7 = Cl, NO 2 or CN are obtained as is, ie by condensation in THF medium, in the presence of ethyl azobisdicarboxylate and triphenylphosphine, of phenethylalcohol of formula

in which R7 has the same meanings as above, with the compound of formula

described in Belgian Patent No. 876,831.

L) The compounds of formula (I) for which the combination (X, A, R1, R2) has the value (O, O, H, CH2 OCH3) and R denotes a benzyloxy group of formula

dans laquelle R"'représente le groupe métabromobenzyloxy, métaiodobenzyloxy, (pyridazinyl-2) méthyloxy, (pyridinyl-3 )méthyloxy, métanitrodideutéro benzyloxy,
paraaminobenzyloxy, (butène-2)oxy, (méthyl-3 butène
2)oxy, (cyclopentène-1 yl-1) méthyloxy, cyclobutyl
méthyloxy, (méthyl-1 cyclopentyl-l) méthyloxy, mor
pholino-2 éthoxy, (tétrahydropyrannyl-3) méthyloxy,
(eyelohexanone-1 yl-4) méthyloxy ou chloro-4 butoxy.wherein R11 = 3-Br, 3-I, 4-NH2, 4-NHCOCH3
or 4-N (CH2) -COCH3,
the metanitrodideuterobenzyloxy group,
the (pyridazinyl-2) methyloxy or (pyridinyl) group
3) methyloxy,
the sequence (butene-2) oxy, (3-methyl-2-butene)
oxy, (cyclopenten-1-yl-1) methyloxy, cyclobutyl
methyloxy, (methyl-1-eyelopentyl-1) methyloxy,
2-morpholino ethoxy, (tetrahydropyranyl-3) methyl
loxy, (cyclohexanone-1-yl-4) methyloxy or chloro-4
butoxy, are obtained
or by condensation of the chloride (or tosylate) of
metabromobenzyl, metaiodobenzyl, (pyridazi)
nyl-2) methyl, (pyridinyl-3) methyl, methanol
trodideuterobenzyl, paraaminobenzyl, para
acetamidobenzyl or para-N-methyl acetamido
zyle; or chlorinated derivative, brominated, mesylated or tosylated
the following alcohols: butene-2 ol-1, methyl-3
butene-2 ol-1, hydroxymethyl-1 cyclopentene, hydro
xymethylcyclobutyl, 1-hydroxymethyl-1-methyl
cyclopentyl, 2-morpholinoethanol, hydroxymethyl
3 tetrahydropyranyl and hydroxymethyl-4 cyclohexa
none; or 1-bromo-4-chlorobutyl, with the
compound of formula (XXVI), preferably in the middle
acetone or acetonitrile and in the presence of carbonate
of potassium, or in DMF medium in the presence
sodium hydride,
- by a so-called phase transfer reaction
on the compound of formula

wherein R "'is metabromobenzyloxy, metaiodobenzyloxy, (2-pyridazinyl) methyloxy, (3-pyridinyl) methyloxy, metanitrodideutero benzyloxy,
paraaminobenzyloxy, (butene-2) oxy, (3-methyl-butene)
2) oxy, (cyclopenten-1-yl-1) methyloxy, cyclobutyl
methyloxy, (methyl-1-cyclopentyl-1) methyloxy, mor
2-pholino ethoxy, (3-tetrahydropyranyl) methyloxy,
(1-Eyelohexanone-4-yl) methyloxy or 4-chlorobutoxy.

The reaction is carried out in the presence of aqueous sodium hydroxide and an organic solvent such as methylene chloride or benzene, using methyl sulfate and a phase transfer catalyst chosen from those mentioned in the reviews. : Synthesis 1973, 441 and Angewandte Chemie
Edit. Int. 13, 170, (1974).

 The compounds of formula (Xa) are prepared according to the process described in Belgian Patent No. 851 893 or French No. 2,356,422.

à partir du composé de formule

également préparé selon le procédé décrit dans le brevet belge n 851 893 ou français n 2 356 422.By this phase transfer method, the compound of formula (I) is also obtained for which the set (X, A, R 1, R 2, R) has the value (O, O, H, CH 2 OCH 3,

from the compound of formula

also prepared according to the process described in Belgian Patent No. 851 893 or French No. 2,356,422.

est obtenu par action du formiate d'éthyle sur le composé de formule (I) pour lequel l'ensemble (X,A,R1,R2,R) prend la valeur (O,O,H,CH20CH3,

préparé selon les procédés décrits au paragraphe L) précédent.M) The compound of formula (I) for which the group (X, A, R1, R2, R) has the value (O, O, H, CH20CH3,

is obtained by the action of ethyl formate on the compound of formula (I) for which the group (X, A, R1, R2, R) has the value (O, O, H, CH20CH3,

prepared according to the methods described in paragraph L) above.

est obtenu par action du chlorure de mésyle en milieu pyridine, sur le composé de formule (I) pour lequel l'ensemble (X,A,R1,R2,R) prend la valeur (O,O,H,CH2OCH3,

The compound of formula (I) for which the group (X, A, R1, R2,
R) takes the value (O, O, H, CH20CH3,

is obtained by the action of mesyl chloride in a pyridine medium, on the compound of formula (I) for which the group (X, A, R1, R2, R) has the value (O, O, H, CH2OCH3,

est obtenu par action du trifluorométhylsulfure de cuivre (CF3SCu) en milieu H.M.P.T., sur le composé de formule (I) pour lequel l'ensemble (X,A,R1,R2,R) prend la valeur (O,O,H,CH20CH3,

et préparé selon les procédés décrits au paragraphe L) précédent.The compound of formula (I) for which the group (X, A, R1, R2,
R) takes the value (O, O, H, CH2OCH3,

is obtained by the action of copper trifluoromethylsulfide (CF3SCu) in HMPT medium, on the compound of formula (I) for which the set (X, A, R1, R2, R) takes the value (O, O, H, CH20CH3 ,

and prepared according to the methods described in the preceding paragraph L).

dans laquelle n prend la valeur 2 ou 3, le composé de formule (XXVII) étant obtenu par condensation du dérivé chloré, bromé, mésylé ou tosylé de l'hydroxyéthyl-2 méthyl-2 dioxolanne-1,3 ou de l'hydroxypropyl-2 méthyl-2 dioxolanne -1,3, de préférence en milieu acétone ou acétonitrile et en pré sence de carbonate de potassium, avec le composé de formule (XXVI).N) The compounds of formula (I) for which the group (X, A, R 1, R 2, R) takes the values (O, O, H, CH 2 OCH 3, CH 3 -Co- (CH 2) 2-o) and (O, O, H, CH 2 OCH 3), CH 4 CO- (CH 2) 4-O) are obtained by acid hydrolysis of the compound of formula

in which n takes the value 2 or 3, the compound of formula (XXVII) being obtained by condensation of the chlorinated, brominated, mesylated or tosylated derivative of 2-hydroxyethyl-2-methyl-1,3-dioxolan or hydroxypropyl- 2-methyl-1,3-dioxolane, preferably in acetone or acetonitrile medium and in the presence of potassium carbonate, with the compound of formula (XXVI).

est obtenu par action du chlorhydrate d'hydroxylamine, en presence at pyrsqine et en milieu éthanolique, sur le composé de formule

lui-même obtenu par condensation du composé de formule (XXVI) et de la chloroacétone, en milieu acétone ou acétonitrile, en présence de carbonate de potassium.The compound of formula (I) for which the group (X, A, R1, R2,
R) takes the value (O, O, H, CH2OCH3,

is obtained by the action of hydroxylamine hydrochloride, in the presence of pyridine and in ethanolic medium, on the compound of formula

itself obtained by condensation of the compound of formula (XXVI) and chloroacetone, in acetone or acetonitrile medium, in the presence of potassium carbonate.

est obtenu par une réaction de transfert de phase avec le sulfate de méthyle sur-le composé de formule

de configuration CR(-)3 et obtenu par action du chlorure de métacyanobenzyle, en solution dans l'acétonitrile (ou l'acéone0, en présence de carbonate de potassium, sur le composé de formule

de configuration R, obtenu par hydrogénolyse, en milieu éthanolique, en pré sence de palladium sur charbon à 5 %, du composé de formule

O) The compound of formula (I) of particular formula

is obtained by a phase transfer reaction with methyl sulfate on the compound of formula

of configuration CR (-) 3 and obtained by the action of metacyanobenzyl chloride, in solution in acetonitrile (or acetone, in the presence of potassium carbonate, on the compound of formula

of configuration R, obtained by hydrogenolysis, in an ethanolic medium, in the presence of 5% palladium on carbon, of the compound of formula

de configuration S, lui-meme obtenu par une synthèse en deux étapes qui consiste à traiter le benzyloxy-3 paratosyloxy-1 propanol-2 de configuration
S(+) par le phosgène en solution dans le dichloroéthane, puis à faire réagir sur le produit intermédiaire formé, la parabenzyloxy aniline.The latter is obtained by cyclization with ethanolic potassium hydroxide of the compound of formula

configuration S, itself obtained by a two-step synthesis which consists of treating the 3-benzyloxy-1-paratosyloxypropanol-2 configuration
S (+) by phosgene in solution in dichloroethane, then to react on the intermediate product formed, parabenzyloxy aniline.

est obtenu par cyclisation par la potasse éthanolique, du composé de formule

de configuration (R).The compound of formula (I) corresponding to the particular formula:

is obtained by cyclization with ethanolic potassium hydroxide, of the compound of formula

configuration (R).

The compound of formula (XId) is prepared by a synthesis analogous to that employed for the synthesis of the compound of formula (XIc) but starting from para (metacyanobenzyloxy) aniline and 3-methoxy-paratosyloxy-1 propanol-2 of R configuration , the latter resulting from the action of tosyl chloride, in a benzene medium and in the presence of pyridine on 3-methoxypropanediol-1,2, of S configuration, itself resulting from debenzylation
Catalytic in ethanolic solution, in the presence of palladium on carbon, benzyloxy-1-methoxy-3-propanol-2 configuration R obtained by opening, with methanol in the presence of boron trifluoride etherate, benzyloxy1 2,3-epoxypropane configuration S (-) described in J. Chem. Soc. 1967, 1021.

dans laquelle R"" représente un groupe métanitrobenzyloxy, métacyanobenzyloxy ou métachloro métanitrobenzyloxy, avec l'ammoniac, l'éthylamine, l'isopropylamine, la morpholine, la pyrrolidine ou la diméthylamine, cette condensation étant de préférence réalisée dans un solvant organique tel que le méthanol.P) The compounds of formula (I) for which the group (X, A, R1) has the value (O, O, H) and R2 represents the isopropylamino methyl, morplolinomethyl, ethylaminomethyl, pyrrolidinomethyl, aminomethyl or dimethylaminomethyl group; are obtained by condensation of compounds of formula

in which R "" represents a metanitrobenzyloxy, metacyanobenzyloxy or metachloro-metanitrobenzyloxy group, with ammonia, ethylamine, isopropylamine, morpholine, pyrrolidine or dimethylamine, this condensation being preferably carried out in an organic solvent such as methanol.

dans laquelle R"" a les mêmes significations que dans la formule (XXX), cette réaction se faisant de préférence en présence de triéthylamine et dans un solvant organique tel que le chlorure de méthylène. Les composés de formule (Xe) sont, pour leur part, obtenus conformément au procédé décrit dans le brevet belge nO 851 893.The compounds of formula (XXX) are in turn obtained by the action of mesyl chloride on compounds of formula

wherein R "" has the same meanings as in formula (XXX), this reaction being preferably in the presence of triethylamine and in an organic solvent such as methylene chloride. The compounds of formula (Xe) are, for their part, obtained according to the process described in Belgian Patent No. 851 893.

la réaction de condensation étant suivie d'une séparation par chromatographie liquide à haute performance (H.P.L.C.) donnant les dérivés érythro et thréo.Q) The compounds of formula (I), erythro or threo, for which the group (X, A, R1) has the value (O, O, H), R2 represents the 1-methoxyethyl chain and R denotes the metacyanobenzyloxy group, metanitrobenzyloxy or benzyloxy, are obtained by treating with methyl sulfate, according to a so-called phase-transfer reaction, the compounds of formula (I), erythro or threo, for which the group (X, A, R 1) is (O, O, H), R2 is 1-hydroxyethyl and R is metacyanobenzyloxy, metanitrobenzyloxy or benzyloxy. These latter compounds are prepared according to the protocol described in Belgian Patent No. 851 893 by the action of chloride, tosylate or mesylate of benzyl, metacyanobenzyl or metanitrobenzyl on the compound of formula

the condensation reaction being followed by separation by high performance liquid chromatography (HPLC) giving the erythro and threo derivatives.

 The compound of formula (Xf) is prepared according to the process used for the synthesis of the compound of formula (Xd), but from 3-benzyloxy-1-tosyloxy-2-butanol rvia parabenzyloxyphenyl-3 (benzyloxymethyl-1) ethyl-5 oxazolidinone 23.

The compound of formula (I) for which the group (X, A, R1, R2) has the value O, O, H, COCH3) is obtained by oxidation with dichloroacetic acid in the presence of dicyclohexanecarbodiimide (DCCI) of mixture of threo and erythro derivatives of compounds of formula (I) for which the set (X, A, R1, R2, R) takes the value

de l'éhylèneglycol, en présence d'acide paratoluène sulfonique, sur les composés de formule

dans laquelle R""' représente un groupe métacyano-, métachloro- ou métanitrobenzyloxy, ou l'enchaînement n-butoxy, cyclopropylméthyloxy, ou cyano-2 éthoxy.R) Compounds of formula (I) for which the set (X, A, R1) takes the value (O, O, H) and the pair (R, R) takes the value

of the ethylene glycol, in the presence of paratoluene sulphonic acid, on the compounds of formula

wherein R ""'represents a metacyano-, metachloro- or metanitrobenzyloxy group, or the n-butoxy, cyclopropylmethyloxy or 2-cyanoethoxy linkage.

dans laquelle R""' a les mêmes significations que dans la formule (XXXI) les composés de formule (Xg) étant, quant à eux, obtenus selon le protocole décrit dans le brevet belge n 851 893 ou français n02 356 422.The compounds of formula (XXXI) are obtained by treatment with dimethylsulfoxide in the presence of DCCI of the compound of formula

in which R "" has the same meanings as in formula (XXXI) the compounds of formula (Xg) being, in turn, obtained according to the protocol described in Belgian Patent No. 851 893 or French No. 356 422.

obtenu selon le protocole décrit dans le brevet belge n 851 893 ou français n 2 356 422, par cyclisation par le carbonate d'éthyle du composé de formule

lui-même obtenu par condensation du glycidol avec la para [(méthyl-4)n- pentylg aniline . Ce dernier composé est obtenu par réduction par le triéthylsilane en présence d'acide trifluoroacétique, de la para Soxo-1- méthyl-4) n-pentyl] aniline, elle-même obtenue par réduction par le fer en présence de chlorure d'ammonium du para [(oxo-i méthyl-4)n-pentyl] nitrobenzène.Ce dernier composé enfin, est préparé selon le procédé employé dans la synthèse du composé de formule (XV) mais à l'aide de la base de Schiff du paranitrobenzaldéhyde, puis du méthyl-3 butanaldéhyde. S) The compound of formula (I) for which the group (X, A, R 1, R 2, R) has the value (O, O, H, CR 2 OCH 3, methyl 4-n pentyl) is obtained by the action of methyl sulphate by a so-called phase transfer reaction, on the compound of

obtained according to the protocol described in Belgian Patent No. 851 893 or French No. 2,356,422, by cyclization with ethyl carbonate of the compound of formula

itself obtained by condensation of glycidol with para [(methyl-4) n-pentylg aniline. The latter compound is obtained by reduction with triethylsilane in the presence of trifluoroacetic acid, para-Soxo-1-methyl-4) n-pentyl] aniline, itself obtained by reduction with iron in the presence of ammonium chloride Finally, this last compound is prepared according to the process employed in the synthesis of the compound of formula (XV) but using the Schiff base of paranitrobenzaldehyde. then 3-methylbutanaldehyde.

 The following preparations are given by way of example to illustrate the invention.

Example 1 para (metanitrobenzyloxy) phenyl-3-ethylcarbonyloxymethyl-5
oxazolidinethione-2 (I)
Code number: 208
A solution of 3 g of para (metanitrobenzyloxy) phenyl-3-hydroxymethyl-5-oxazolidinethione-2 (II), 0.83 ml of propionyl chloride and 3 ml of triethylamine in 100 ml THF Then filtered, evaporated the filtrate and crystallized the residue in ethyl ether. 2.5 g of the expected product are thus obtained.

Yield: 73%
Melting point: 1260 ° C
Gross formula: C20H20N206S
Molecular weight: 416.44
Elemental analysis

<SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 57.68 <SEP> 4.84 <SEP> 6.73
<tb> Found <SEP> (%) <SEP> 57.59 <SEP> 5.03 <SEQ> 6.69
<Tb>
By the same method, but from the corresponding reagents, there is obtained the compound of formula (I) of code number 178 shown in Table I below, as well as the compound of formula (IX).

Example 2 para (3-methyl-butoxy) -3-phenyl-5-methoxymethyl oxazolidinethione-2
(I)
Code number: 214
1st stage: para (3-methylbutoxy) 1-anilino-3-methoxypropanol-2
(III)
A solution of 19.8 g of para (3-methyl-butoxy) aniline (IV) and 9.7 g of 1-chloro-3-methoxy-2-propanol in 160 ml of ethanol is refluxed for five hours. Then, the solvent is evaporated and the residue is distilled under vacuum. 10.5 g of the expected product are obtained.

Yield: 35% NMR Spectrum (DMSO): ## ppm =
Aromatic 6,6, m, 4H,
4.8, d, 2 H exchangeable (OH and NH)
3.8, s + m, 3H - CH2-O-Ar and -CH-OH
3.3, d + s, 5H, CH 2 -O-CH 3 and CH 2 O 3, m, -CH 2 -N; 1.7, m, 3H and 0.9, d, 6H

CH2
By the same method, but from the corresponding reagents, the compound of formula (IIIb) is prepared.

3rd stage: para (3-methyl-butoxy) 3-phenyl-5-methoxymethyl
oxazolidinethione-2 (I)
Code number: 214
To a solution cooled to 50 ° C. of 10.5 g of the above compound (III) and 11.9 g of triethylamine in 150 ml of THF, 3 ml of thiophosgene are slowly added. Then allowed to warm to room temperature, filtered, evaporated the solvent and chromatography the residue on a silica column (eluent = methylene chloride). 3.6 g of an oil are thus isolated.

Yield: 30%
Gross formula: C16H23NO3S
Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 62.10 <SEP> 7.49 <SEP> 4.53
<tb> Found <SEP> (%) <SEP><SEP> 62.41 <SEP> 7.61 <SEP> 4.45
<Tb>
By the same method, but from the corresponding reagents, the compounds of formula (I) appearing in Table I and having the code numbers: 209 to 213 and 215 to 218 are obtained.

Example 3 para ((metanitro) benzyloxy] phenyl-3-methoxymethyl-5
thiazolidinone-2 (I)
Code number: 219
1st stage: para [(metanitro) benzyloxy] anilino-3-methoxy-1
propanethiol-2, oxalate (VI)
To a solution of 48.8 g of para [(metanitro) benzyloxy] aniline in 700 ml of isopropanol is slowly added 20.8 g of 2-methoxymethylthiooxirane, then refluxed for 7 hours. Then, the solvent is evaporated and the residue is chromatographed on a silica column. After elution with 100% methylene chloride, 38.4 g of oil are obtained, which is dissolved in acetonitrile. A solution of oxalic acid in acetonitrile is added and the precipitate obtained is filtered off.

Yield: 43%
Melting point: 1200 C
Crude formula: C 19H22N2Q8S Molecular weight: 438.45 Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 52.04 <SEP> 5.06 <SEQ> 6.39
<tb> Found <SEP> (%) <SEP> 51.79 <SEP> 4.88 <SEP> 6.48
<Tb>
2nd stage: para [(metanitro) benzyloxy] phenyl-3-methoxymethyl-5
thiazolidinone-2 (I)
Code number: 219
To a solution cooled to -10 ° C. of 3 g of phosgene in 90 ml of dichloroethane, 4.14 g of potassium carbonate are added, followed by 6 g of compound (YI) (base form) obtained in the preceding stage, dissolved. in 50 ml of dichloroethane while maintaining the temperature between 5 and 100 C. Then it is slowly allowed to return to ambient temperature (3 hours), water is added, the organic phase is decanted, the dried layer is dried over sodium sulphate and the solvent is evaporated off. The residue is crystallized from isopropyl ether and recrystallized from isopropyl alcohol. 3 g of the expected product are thus isolated.

. Yield: 47%
Melting point: 740 ° C
Gross formula: C18H18N2Q5S
Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 57.74 <SEQ> 4.85 <SEP> 7.48
<tb> Found <SEP> (%) <SEP> 57.45 <SEP> 4.97 <SEP> 7.18
<Tb>
EXAMPLE 4 N-Parabenzyloxyphenylhydroxymethyl-3-pyrrolidine (I)
Code number: 220
A solution of 53 g of the compound (VII) in 300 ml of anhydrous tetrahydrofuran is added while cooling to 11.8 g of lithium aluminum hydride (in pellets) in 1000 ml of tetrahydrofuran. Then refluxed for two hours, then added successively 6.3 ml of water, 4.75 ml of 20% sodium hydroxide and then 22 ml of water. The mixture is filtered, the filtrate is evaporated and the residue is crystallized from ethyl acetate. Is thus isolated 38 g of the expected product.

Yield: 85%
Melting point: 870 C Formula crude: C18H21N02 Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 76.29 <SEP> 7.47 <SEP> 4.94
<tb> Found <SEP> (%) <SEP> 76.40 <SEP> 7.60 <SEP> 4.65
<Tb>
Example 5 para (4-aminobenzyloxy) phenyl-3 (1,1-dimethyl) ethylcarbonyloxy
methyl-5 oxazolidinone-2 (Ic)
Code number: 235
To a suspension of amalgam of mercury-aluminum in 300 ml of ether saturated with water, 10.3 g of compound (IX) obtained by a process identical to that described in Example 1, but from compound (x)] so as to maintain a reflux of the ether.Then 25 ml of water are slowly added, left overnight at room temperature, then filtered, the filtrate is evaporated and the residue is recrystallized from isopropyl alcohol. 7.6 g of the expected product are thus isolated.

Yield: 84%
Melting point: 880 ° C
Gross formula: C22H26N2O5
Elementary analysis

<tb> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 66.31 <SEP> 6.58 <SEP> 7.03
<tb><SEP> Found <SEP> (%) <SEP><SEP> 66.28 <SEP> 6.75 <SEP> 6.90
<Tb>
Example 6 para [(n-formylamino-4) benzyloxy] phenyl-3 (1,1-dimethyl)
ethylearbonyloxymethyl-5-oxazolidinone-2 (I)
Code number: 236
A solution of 5.2 g of the above compound (lc) in 80 ml of ethyl formate is brought to 300 ° C. for 12 hours. The solvent is then evaporated under vacuum and the residue is dissolved in ethyl acetate. washed with water, dried over sodium sulfate, filtered, evaporated the solvent and recrystallized the residue in absolute alcohol. 1.5 g of the desired product are thus isolated.

. Yield: 27%
Melting point: 1580 ° C
Gross formula: C23H26N206
Elemental analysis

<tb><SEP> C <SEP> H <SEP> | <SEP> N
<tb> Calculated <SEP> (%) <SEP> 64.77 <SEP> 6.15 <SEP> 6.57
<tb> Found <SEP> (%) <SEP><SEP> 64.47 <SEP> 6.32 <SEP> | <SEP> 6.49
<Tb>
By the same method, but from the corresponding reagents, there is obtained the compound (I) of code number 246, appearing in Table I below.

Example 7: 3-biphenyl-5-methoxymethyloxazolidinone-2 (I)
Code number: 195
To a solution of 6.3 g of 2-biphenylaminocarbonyloxy-1-chloro-3-methoxypropane (XI) (the preparation of which is described later in Example 9) in 150 ml of ethanol, 1.3 g of potassium hydroxide are added. (in pellets), and left at room temperature for two hours. Then it is diluted with water, extracted with ethyl acetate, dried over sodium sulphate, filtered, the filtrate is evaporated and the residue is recrystallized from a mixture of ethyl ether (60%) and absolute alcohol (40%).

. Yield: 75%
. Melting point: 1200 C
. Gross formula: C17H17N03
. Elemental analysis:

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 72.06 <SEP> 6.05 <SEQ> 4.94
<tb> Found <SEP> (%) <SEP><SEP> 72.27 <SEP> 5.91 <SEQ> 4.62
<Tb>
By the same method, but starting from the corresponding reagents, the compounds of formula (I), appearing in Table I below, and of code numbers: 187, 190, 191, 193, 194, 196, 269, are obtained. 274, 276, 278, 284, 270 and 287, as well as the compounds of formulas (XIX). (XXI), (XXIX), and (Ib), the latter appearing in Table I under the code number 200.

Example 8 para (Transmetachlorostyryl) 3-Phenyl Methoxymethyl-5
oxazolidinone-2 (I)
Code number: 190
A solution of 1.6 g of para (1-propetro-chloro-styryl) -1-anilino-3-methoxy-2-propanol (IIIb) (obtained according to the method described in the first stage of Example 2) is slowly added in 25 ml of dichloroethane to a mixture of solution refluxed with 0.95 ml of ethyl chloroformate in 25 ml of dichloroethane. The mixture is refluxed for three hours, then the solvents are evaporated under vacuum and the crude N-carbethoxy-para (transmetachlorostyryl) anilino-1-methoxy-3-propanol-2 (IIIa) thus obtained is dissolved in 150 ml of toluene.

The solution was refluxed and slowly added 10.5 ml of a 5% solution of sodium methoxide in methanol. Then the mixture is refluxed for 30 minutes, the solvents are evaporated off, the residue is taken up in ethyl acetate, washed with water, dried over sodium sulfate, filtered, the solvent is evaporated off and the residue is recrystallized from absolute alcohol.

Yield: 30%
Melting point: 1360 ° C
Gross formula: C19H18C1N03
Elemental analysis

<SEP> C <SEP> H <SEP> N
<tb> Caleulé <SEP> (%) <SEP> | <SEP> 66.37 <SEP> 5.28 <SEP> 4.07
<tb> Found <SEP> (%) <SEP> | <SEP> 66.08 <SEP> 5, <SEP> 24 <SEP> 3.90
<Tb>
By the same method, but from the corresponding reagents, the compounds of formula (I) appearing in Table I below and of code numbers: 187, 191, 193, 194, 195, 196, 269, are obtained. 270, 274, 276, 278, 284 and 287.

Example 9: 2-biphenylaminocarbonyloxy-1-chloro-3-methoxypropane [(XI),

We're wearing 40
C. a solution of 5 g of phosgene and 5.3 ml of 1-chloro-3-methoxy-2-propanol in 100 ml of dichloroethane, then 8 ml of diethylaniline are added and the solution is brought to 65-70 ° C. for 2 hours. 30 minutes.

dissous dans 100 ml de dichloréthane et laisse 1 heure à 40 C. Puis on dilue avec de l'eau, ajoute de la soude 1N jusqu'à disparition du précipité formé, filtre, décante la phase organique, sèche sur sulfate de sodium, filtre, évapore le solvant et recristallise le résidu dans un mélange 50/50 d'éther de pétrole et de toluène.Then water is added, the organic phase is decanted, washed with water, dried over sodium sulphate, filtered and the solution is heated to 400 ° C. 8.5 g of biphenylamine are then added.

dissolved in 100 ml of dichloroethane and left for 1 hour at 40 ° C., then diluted with water, added 1N sodium hydroxide until the precipitate formed disappeared, filtered, decanted the organic phase, dried over sodium sulfate, filtered evaporate the solvent and recrystallize the residue in a 50/50 mixture of petroleum ether and toluene.

. Yield: 41%
# Melting point = 1160 ° C
By the same process, but from the corresponding reagents, the compounds (XI) for which R "represents phenyl, metachlorophenyl, parachlophenyl and metacyanophenyl groups, as well as the compounds of formulas (XIa), (XIb) (XIc), are obtained. , (XId).

Example 10 Para (Parachlorophenyl) Aniline

 To a solution of 2 × 4 g of parachlorophenyl nitrobenzene in 50 ml of ethanol is added 2.5 g of iron filings and 60 ml of a 0.1 M aqueous solution of ammonium chloride. Then refluxed for 1 hour, filtered, extracted with ethyl acetate, washed with water, dried over sodium sulfate, filtered and the solvent evaporated. 2 g (95%) of product are obtained.

dans laquelle R'3 a les significations mentionnées pré cedemment ; le composé de formule (I) figurant dans le tableau I et portant le numéro de code 240 les composés de formule (IVa) pour lesauels R" représente le groupe de structu

laquelle R'7 a les significations précédemment mentionnées ; ainsi que ls para (méthyl-4 one-1 n-pentyl-1) aniline utilisé dans l'exemple 16 ci-après.By the same method, but from the corresponding reagents, the compounds of formula (IVa) for which R "represents the structural group are obtained.

in which R'3 has the meanings mentioned above; the compound of formula (I) shown in Table I and having the code number 240 the compounds of formula (IVa) for those R '' represents the group of

which R'7 has the previously mentioned meanings; as well as para (4-methyl-1-n-pentyl-1) aniline used in Example 16 below.

Example 11 para (metanitrophenyl) aniline

1st stage: oxime of para (metanitrophenyl) acetophenone
Refluxed for 2 hours, a solution of 2.4 g of para (metanitrophenyl) acetophenone and. 1.96 g of hydroxylamine hydrochloride in 15 ml of anhydrous pyridine and 5 ml of absolute alcohol. Then, the solvents are evaporated under vacuum, the residue is diluted with water, the precipitate formed is filtered off and recrystallized from absolute alcohol. So we get? g of the product means.

By the same method, but from the corresponding reagents, there is obtained the compound of formula (I) -figurant in Table I and bearing the code number 260 (from the compound XXVIII). 2nd stage: para (metanitrophenyl) aniline

To a suspension of 2 g of the above compound in 100 ml of benzene is added 4.8 g of phosphorus pentachloride and refluxed for 20 minutes. Then, hydrochloric ethanol (8 ml of concentrated HCl in 160 ml of ethanol) is added and the solution is refluxed for 2 hours 30 minutes. The solvents are then evaporated off, the residue is taken up in water and aqueous sodium hydroxide. extracted with ether, dried over sodium sulfate, filtered, evaporated the solvent and crystallized the residue in absolute alcohol. 1 g of the desired product used as such is obtained in the synthesis of the corresponding compounds (XI) and (Tub).
Example 12 Para (Transmetanitrostyryl) Aniline

1st stage: metanitrophenyltriphenylphosphonium chloride (XIII),
R10 = NO2J
A solution of 112.5 g of metanitrobenzyl chloride and 206.5 g of triphenylphosphine in 100 ml of isopropyl ether is refluxed for two hours and the precipitate obtained is filtered off.

Yield: 48%
By the same method, the compounds of formula (XIII) for which R10 has the abovementioned meanings are obtained.

2nd stage: para (cis and trans metanitrostyryl) acetanilide (xii),
R10 = NO2]
To a solution of 26.5 g of the above compound (XIII) and 10 g of paraformylacetanilide in 700 ml of ethanol, a solution of 1.4 g of sodium in 200 ml of ethanol is added slowly, and room temperature for ho hours. Then, the mixture is filtered, the filtrate is evaporated and the residue is chromatographed on a silica column (eluent: methylene chloride). The desired product is obtained in an overall yield of 27%, comprising 28% of the trans compound and 72% of the cis compound.

 By the same method, but from the corresponding reagents, the compounds of formula (XII) for which R10 has the same meanings as in the compounds of formula (XIII) are obtained.

3rd stage para (tranemetanitroethyl aniline I (IVa),

 A solution of 7.3 g of the above compound (XII), trans (R10 = NO2), in 50 ml of ethanol and 100 ml of 2N hydrochloric acid is refluxed for 6 hours. The precipitate formed is then filtered off, dissolved in an aqueous 2N sodium hydroxide solution, extracted with ethyl acetate, dried over sodium sulfate, filtered, the filtrate is evaporated and the residue is crystallized from isopropyl ether. 70% of product is obtained.

cis ou trans, dans laquelle R10 a les mêmes significations que précédemment.Melting point: 1800 C
By the same method, but from the corresponding reagents, we obtain the compounds (IVa) for which R "represents the groups of structure

cis or trans, in which R10 has the same meanings as before.

Example 13: para [(metacyano benzoyl) methyl] nitrobenzene [(XV), R'7 = CN]
1st stage: &alpha; -phenylamino) metacyanobenzyl acid ester
diphenylphosphorous [(XVI), R'7 = CN]
To a solution of 35 g of compound (XVII) (R'7 = CN), in 300 ml of ethanol is added 40 g of diphenyl phosphite and allowed to stir at room temperature for 12 hours. Then it is diluted with ether and filtered the precipitate formed. 37.8 g (56%) of crude product are obtained.

 By the same method, but from the corresponding reagents, the compound of formula (XVIa) and the para (4-methyl-1-n-pentyl-1) nitrobenzene used in Example 10 are obtained.

2nd stage: para [(metacyanobenzoyl) methyl nitrobenzenetXV), R'7 =
To a solution of 37 g of the above compound (XVI) in 600 ml of THF, 5 g of potassium hydroxide in 50 ml of ethanol is added. The solution is refluxed and 12.7 g of paranitrobenzaldehyde are slowly added and allowed to reflux for 8 hours. Then the organic phase is decanted, evaporated and the residue is diluted in concentrated hydrochloric acid, then water and ethyl acetate are added, the organic phase decanted, washed with water, dried over sodium sulfate, filter, evaporate the solvent and crystallize the residue in methanol. 9 g of the desired product are thus isolated.

Yield: 40%
Melting point: 1700 C
The product is used as such in the synthesis of the corresponding compound (IVa).

 By the same method, but starting from the corresponding reagents, the compounds of formula (XV) for which R'7 has the meanings mentioned above, as well as the compound of formula (I) appearing in Table I below, are obtained. bearing the code number 283.

EXAMPLE 14: 3-paraformylphenoxymethyl-5-oxazolidinone-2 (XVIII)
To a solution of 3.5 g of compound (XIX) in 100 ml of THF is added 2 ml of concentrated hydrochloric acid and stirred at room temperature overnight. Then, the solvents are evaporated and the residue is crystallized in isopropyl alcohol. 2.2 g (63%) of compound (XVIII) are obtained.

. Melting point: 720 ° C
. Gross formula: C12H13N04
Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 61.27 <SEP> 5.57 <SEP> 5.95
<tb> Found <SEP> (%) <SEP> 61.13 <SEP> 5.55 <SEP> 5.88
<Tb>
By the same method, but from the corresponding reagents, the compound of formula (XXIII) mentioned in Example 17 is obtained, and the compounds of formula (I), appearing in Table I and bearing code numbers 237 and 238.

Example 15: para [(metachlorophenyl) ethynyl] phenyl-3-methoxyxethyl-5
oxazolidinone-2 (I)
Code number: 277
1st stage: metachlorophenyl ethynyl
To a solution of 18 g of the semicarbazone of metachloroacetophenone (XXII), R5 = 3-Cl] in 170 ml of acetic acid, heated to 350 ° C., 10.5 g of selenium. Then heated at 800C for two hours, and poured into 1 1 of water. It is extracted with methylene chloride, washed with saturated sodium bicarbonate solution, then with water, dried over sodium sulphate, filtered, the filtrate is evaporated and the residue is recrystallized from a 50/50 mixture of petroleum ether and The product thus obtained (12.6 g, yield = 61%) is mixed with 20 g of Fontainebleau sand and the mixture is slowly brought to 1500 C under vacuum. The desired product is thus distilled.

. Boiling point Eb160 = 110 C
. Yield: 69%
2nd stage: copper salt of metachlorophenylethynyl [(XX),
R5 = 3-ClJ
To a solution of 36.9 g of copper sulphate (pentahyurate) in 200 ml of ammonia and 500 ml of water is added 20.6 g of hydroxylamine hydrochloride. It is then cooled to 0 ° C. and a solution of 20.2 g of the compound obtained in the preceding stage is slowly added to 800 ml of ethanol. Then ethyl acetate is added, and the precipitate formed is filtered off and washed with water on the filter and dried under vacuum.

Yield: 86%
By the same method, but from the corresponding reagents, the other compounds of formula (XX) and the compounds of formulas (XXa) and (XXb) are obtained.

3rd stage: para (metachlorophenyl) ethynyld phenyl-3 methoxy
5-methyl-oxazolidinone-2 (I)
Code number: 277
A suspension of 4.8 g of the above compound (XX) and 6.7 g of the compound (XXI) in 100 ml of hexamethyl * nephosphotriamide (MMPT) is heated at 220 ° C. under nitrogen for 90 minutes. . Then it is poured into water, extracted with ethyl acetate, washed with an aqueous solution of potassium iodide, then with water, dried over sodium sulphate, filtered, the solvent is evaporated and the residue is recrystallized. in methanol and then in ethyl acetate.

. Yield: 50%
. Melting point: 1200 C
. Gross formula: C19H16C1N03
. Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 66.76 <SEP> 4.72 <SEQ> 4.10
<tb> Found <SEP> (%) <SEP> 66.20 <SEK> 4.64 <SEP> 4.04
<Tb>
By the same method, but from the corresponding reagents, the compounds of formula (I) appearing in Table I and having the code numbers: 189, 261, 262, 268, 280, 281, 282 are obtained.

Example 16 para (metacyanophenyl) phenyl-3-methoxymethyl-5-oxazolidinone-2 (i)
Code number: 272
To a mixture of 1.2 g of compound (I) of code number 270, and 2.2 ml of triethylsilane, 6 ml of trifluoroacetic acid are added and the mixture is kept at room temperature for 2 hours. Then poured on ice and water, neutralized with sodium carbonate solution, extracted with ethyl acetate, washed with water, dried over sodium sulfate, filtered, the solvent evaporated and recrystallized the product in absolute alcohol.

. Yield: 40%
. Melting point: 1020 C
. Gross formula: C20H20N203
. elementary analysis

<tb> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 71.41 <SEP> 5.99 <SEP> 8.33
<tb> Found <SEP> (%) <SEP> 71.51 <SEP> 5.90 <SEP> 8.37
<Tb>
By the same method, but from the corresponding reagents, the compounds of formula (I), appearing in Table I and carrying the code numbers: 192, 271 and 279, as well as para (methyl-4 n-) are obtained. pentyl-1) aniline used in Example 28.

Example 17 para (hydroxymethyl) phenyl-3-methoxymethyl-5-oxazolidinone-2
(XXIII)
To an ethanolic solution of 37.4 g of compound (XVIII) in 200 ml of ethanol is added slowly 12 g of sodium hydrobromide then refluxed for 2 hours, the solvent is evaporated, the residue is taken up in water, extracted with ethyl acetate, washed with water, dried over sodium sulfate, filtered and the solvent evaporated. 54% of the expected product is obtained.

. Melting point: 700 ° C
. Gross formula: C12H15N04
. Elemental analysis

<SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 60.75 <SEP> 6.37 <SEP> 5.90
<tb> Found <SEP> (%) <SEP> 60.71 <SEP> 6.31 <SEP> 6.12
<Tb>
Example 18 para (metachlorophenoxymethyl) 3-phenyl-5-methoxymethyloxazol
dinone-2 (I)
Code number: 273
To a solution of 2.4 g of the above compound (XXIII) in 50 ml of
THF, 2.6 g of triphenylphosphine and 1 g of metachlorophenol are added. The solution is cooled to 00 ° C. and ethyl azobisdicarboxylate (1.6 ml) is added.

The solution is then left at ambient temperature and after 4 hours refluxed (2 hours), filtered, the filtrate is evaporated, the residue is taken up in methylene chloride and the solution is chromatographed on a silica column. 0.6 g (22%) of product recrystallized from absolute alcohol are obtained.

Melting point: 820 ° C. Gross formula: C18H18ClN04
. Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb><SEP> Calculated <SEP> (%) <SEP> 62.16 <SEP> 5.22 <SEP> 4.03
<tb> Found <SEP> (%) <SEP> 62.22 <SEP> 5.26 <SEP> 4.01
<Tb>
By the same method, but from the corresponding reagents, the compounds of formula (I), appearing in Table I and bearing the code numbers: 239 and 275 as well as those bearing the code numbers: 264, 263, are obtained. 267, but from the compounds of formulas (XXV) and (XXVI).

Example 19 para (metaiodobenzyloxy) -3-phenyl-5-methoxymethyl
oxazolidinone-2 (I)
Code number: 198
A suspension of 10 g of compound (XXVI), 12 g of metaiodobenzyl chloride and 20 g of sodium carbonate in 300 ml of acetone is refluxed for 9 hours. Then the mixture is filtered, the filtrate is evaporated, the residue is taken up in water, the precipitate formed is filtered and recrystallized in alcohol. 16.5 g of the expected product are thus obtained.

. Yield: 78%
. Melting point: 1180 ° C
. Gross formula: C18H18NI04
. Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 49.22 <SEP> 4.13 <SEP> 3.19
<tb> Found <SEP> (%) <SEP> 49.39 <SEP><SEP> 4.08 <SEP>#<SEP> 3.13
<Tb>
By the same process, but from the corresponding reagents, the compounds of the formula (I), given in Table I and having the code numbers 179, 181 to 186, 188, 197, 234, 241, 242, are obtained. 244, 247, 285, 286, 255, 256, as well as the compounds of formula (Xc), (XXVII), (XXVIII).

Example 20 Paradimethylaminophenyl-3-Methoxymethyl-5-oxazolidinone-2 (I)
Code number: 180
To a solution of 4.5 g of compound (Xb) in 40 ml of methyl sulfate chloride, then 40 ml of methylene are slowly introduced, 3.8 g of 50% sodium hydroxide solution are added and the mixture is shaken. for 3 hours at room temperature. Then decanted, the organic phase washed with water, dried over sodium sulfate, filtered, evaporated the filtrate and chromatography the residue on a silica column (eluent: ethyl acetate).

There is thus obtained 2.8 g of the desired product recrystallized from isopropyl alcohol.

. Yield: 59%
. Melting point: 920 C
. Gross formula: C13H18N203
Elemental analysis

<tb> C <SEP> H <SEP> N
<tb><SEP> Caleulate <SEP> (%) <SEP> 62.38 <SEP>#<SEP> 7.25 <SEP> 11.19
<tb><SEP> Found <SEP> (%) <SEP> 62.45 <SEP> 6.98 <SEP> 10.94
<Tb>
By the same method, but from the corresponding reagents, the compounds of the formula (I), given in Table I and having the code numbers: 179, 181 to 186, 188, 197, 198, 234, 241, are obtained. 242, 244, 247, 285, 286, 258, 259, 265, 266, 288, as well as the compound (Ia), of code number 199 also included in Table I.

Example 21 para L (paramethylsulfonylamino) benzyloxy] phenyl-3-methoxymethyl-5
oxazolidinone-2 (I)
Code number: 243
To a solution of 3.3 g of compound (I) of code number 242 in 60 ml of pyridine, 1.3 ml of methanesulfonyl chloride are slowly added.

The mixture is then stirred for 3 hours, diluted with water, the precipitate formed is filtered and recrystallized from absolute alcohol. 2.4 g of product are thus isolated.

# Yield: 59%
Melting point: 142 ° C
Gross formula: C19H22N2O6S
Elemental analysis:

<SEP> C <SEP> H <SEP> N
<tb><SEP> Calculated <SEP> (%) <SEP> 56.14 <SEP> 5.46 <SEP> 6.89
<tb> Found <SEP> (%) <SEP> 56.34 <SEP> 5.56 <SEP> 6.94
<Tb>
Example 22: para k: metathifluoromethylthio) benzyloxy] phenyl-3-methoxymethyl-5
oxazolidinone-2 (I)
Code number: 245
A mixture of 14 g of compound (I) of code number 198 and 12 g of copper salt of trifluoromethylthiol (CF 3 SCu) is heated under a stream of nitrogen at 1500 ° C. for 18 to 20 hours. and in 80 ml of HMPT.

dilute the filtrate with ethyl acetate and water, decant the organic phase, dry over sodium sulfate. filter, evaporate the solvent and recrystallize the residue in isopropyl ether. 7 g of the expected product are thus obtained.

Round: 53%. Melting point: 84 ° C. Gross formula: C19H18F3NO4S. Elemental analysis:

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (5) <SEP> 55.20 <SEP> 4.39 <SEP> 3.39
<tb> Found <SEP> (%) <SEP> 55.50 <SEP> 4.43 <SEP> 3.49 <SEP>
<Tb>
Example 23: para-hydroxyphenyl-3-hydroxymethyl-5-oxazolidinone-2
R configuration (Xd)
The mixture is hydrogenolyzed in an autoclave, at room temperature, under a pressure of 4 to 5 kg of hydrogen, a suspension of 18 g of compound (XXIX) and 2 g of 10% palladium on carbon in 400 ml of absolute alcohol. Then filtered, evaporated the solvent and recrystallized the residue in absolute alcohol. (Yield = 62%, mp = 1880 ° C). By the same method, but from the corresponding reagents, the compound of formula (XI), employed crude in the synthesis of the corresponding compounds (I) is obtained.

EXAMPLE 24 Paratoluene 1-sulfonyloxy-3-methoxy-2-propanol of R-configuration

1st stage: methoxy-1-hydroxy-2-benzyloxy-3 propane R (+)
To a solution cooled to 5 ° C. of 4.14 g of 3-benzyloxy-1,2-epoxypropane in 40 ml of methanol, 3 drops of boron trifluoride etherate are added. Then let cool slowly to room temperature (3 hours).

A little sodium bicarbonate is added, the solvent is evaporated, the residue is taken up in 200 ml of water, extracted with methylene chloride, dried over sodium sulphate and the solvent is evaporated off. This residue is chromatographed by H.P.L.C.

 [sio2; 15-25 / S; eluent: ethyl acetate (60%) - n-heptane (40%)], then distilled Ebo 1 = 17500. 70% of the product is obtained.

DD = t44 (C = 5, Ethanol); gross formula: C11H1603
2nd stage: 3-methoxypropanediol-1,2 (S)
A solution of 4.44 g of the compound obtained in the preceding stage is hydrogenolyzed under a pressure of 5 kg and at a temperature of 30 ° C. in the presence of 0.5 g of 10% palladium on carbon. ethanol and 1 drop of hydrochloric ethanol. Then filtered, added a little bicarbonate to the filtrate, evaporated the solvent, the residue in ether, washed with water, dried over sodium sulfate and evaporated the solvent. 2.37 g of product are obtained after chromatography of the crude product by HPLC.

[SiO2; eluent: ethyl acetate (60%) - n-heptane (40%)
3rd stage: p-toluenoxy-1-hydroxy-2-methoxy-3-propane (R).

 To a solution cooled to 00 ° C. of 2.37 g of the compound obtained in the preceding stage in 10 ml of pyridine, a solution of 4.27 g of tosyl chloride in 50 ml of benzene is slowly added. It is then left for 40 hours at room temperature, diluted with ether, filtered and the filtrate washed with 1N hydrochloric acid, then with water and with an aqueous solution of sodium bicarbonate until neutral. . Then dried over sodium sulfate and evaporated the solvent. The residue is chromatographed by H.P.L.C.

[eluent: ethyl acetate (60%) - n-heptane (40%)
Yield = 53%.

 The product is used directly in the synthesis of the compound of formula (XId).

Example 25 para (metanitrobenzyloxy) -3-phenyl-5-isopropylaminomethyl
oxazolidinone-2 (I)
Code number: 201 1st stage: Para (metanitrobenzyloxy) hexyl-R 5-hydroxy-5-oxazolidinon mesylate

To a solution of 17.2 g of the compound (600 ml of methylene chloride) is added 10.2 g of triethylamine and then 11.45 g of mesyl chloride (in 50 ml of methylene chloride) while cooling to 50 ° C. leaves in contact for 30 minutes, then it is thrown in water, decanted the organic phase, dried over sodium sulfate, filtered, evaporated the solvent and recrystallized the residue in ethyl acetate.

. Yield: 80%
. Melting point: 1190 C.

 By the same method, but from the corresponding reagents, the compounds of formula (XXX) are obtained for which R "'has the meanings mentioned above.

2nd stage: para (metanitrobenzyloxy) phenyl-3 isopropylamino
5-methyl-oxazolidinone-2 (I)
Code number: 201
A mixture of 6.3 g of the above compound (XXX) and 5 ml of isopropylamine in 80 ml of methanol is heated at 2000 ° C. in an autoclave for 3 hours 30 minutes. The solvent is then evaporated, the residue is taken up in water and extracted with ethyl acetate, the solvent is evaporated and the residue is chromatographed on a silica column. Elution with chloroform (99%) methanol (1%) gives 36% of product (I) recrystallized from isopropyl ether / isopropyl alcohol (50-50).

. Melting point = 760 ° C
. Gross formula: C20H23N305
Elemental analysis

<SEP> C <SEP> H <SEP> N
<tb><SEP> 1
<tb><SEP> Calculated <SEP> (%) <SEP> 62.32 <SEP> 6.02 <SEP> 10.90
<tb> Found <SEP> (%) <SEP> 62.04 <SEP> 5.90 <SEP> 10.75
<Tb>
By the same method, but from the corresponding reagents, the compounds of formula (I) appearing in Table I and bearing the code numbers: 202 to 207 are obtained.

Example 26: acetyl-5-para (metanitrobenzyloxy) phenyl-3 oxazolidinone-2 (I)
Code number: 257
To a solution of a mixture of 15 g of compounds (I) of code numbers 255 and 256 (threo and erythro) in 80 ml of dimethylsulfoxide and 200 ml of ethyl acetate is added 25.3 g of dicyclohexylcarbodiimide (dissolved in 600 ml of ethyl acetate). The mixture is left in contact at ambient temperature for 90 minutes and then, in the course of 15 minutes, 4.05 g of dichloroacetic acid are added. The mixture is left stirring at room temperature for 20 hours, then 11 g of oxalic acid are introduced over 20 minutes and left in contact for 1 hour. Then it is filtered, the filtrate is washed with sodium bicarbonate solution, with water, dried over sodium sulfate, filtered, the solvent is evaporated and the residue is chromatographed on a silica column. Elution with ethyl acetate mixture (80%) - heptane (20%) and then recrystallization from ethyl acetate, 8 g (55%) of product are obtained.

. Melting point: 1070 C
. Gross formula: C18H16N206
. Elemental analysis

<tb> C <SEP> H <SEP> N
<tb><SEP> Calculated <SEP> (%) <SEP> 60.67 <SEP> 4.53 <SEP> 7.86
<tb><SEP> Found <SEP> (%) <SEP><SEP> 60.90 <SEQ> 4.29 <SEP> 7.74
<Tb>
Example 27: (dimethoxy-1, 1) methyl-5-para (metanitrobenzyloxy) phenyl-3
oxazolidinone-2 (I)
Code number: 248 lez stage: para (metanitrobenzyloxy) nhénvl-R (dihydroxy-11) methyl-5-oxazolidinone-2

To a solution of 10.3 g of compound 60 ml of dimethylsulfoxide and 300 ml of ethyl acetate is added 18.6 g of dicyclohexylcarbodiimide (DCCI), then in 10 minutes, 1 ml of 85% phosphoric acid. and left at room temperature for 20 hours.

Then diluted with 300 ml of ethyl acetate and added slowly 8.1 g of oxalic acid. The mixture is left in contact for 1 hour, then the organic phase is decanted, the washing is washed with water, and with sodium bicarbonate solution, dried over sodium sulfate, filtered, the solvent is evaporated and the residue is chromatographed on a silica column. After elution with a mixture of methylene chloride (98%) and methanol (2%), 33% of product is obtained.

 Melting point: 1000 C.

 By the same method, but from the corresponding reagents, compounds (XXXI) are obtained for which R '' '' has the meanings mentioned above.

2nd stage: (dimethoxy-l, l) methyl-5 para (metanitrobenzyloxy)
3-phenyloxazolidinone-2, (I)
Code number: 248
A solution of 7.2 g of the above compound (XXXI) in 100 ml of 0.25N hydrochloric methanol is refluxed for 21 hours. Then the solvent is evaporated, the residue is taken up in ethyl acetate, washed with water, dried over sodium sulfate, filtered, the solvent is evaporated and the residue is chromatographed on a silica column. After elution with methylene chloride and recrystallization from isopropanol, 3.9 g (50%) of product are obtained.

. Melting point: 1180 ° C
. Gross formula: Cl9H20N207
Elemental analysis

<tb><SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 58.76 <SEP> 5.19 <SEP> 7.21
<tb> Found <SEP> (%) <SEP> 58.64 <SEP> 5.01 <SEP> 7.37
<Tb>
By the same method, but from the corresponding reagents, the compounds of formula (I), shown in Table I and having code numbers: 249 to 254 are obtained.

Example 28 para (4-methyl-n-pentyl-1) -phenyl-3-hydroxymethyl-5-oxazolidinone-2 (xh)
it is prepared from para (4-methyl-n-pentyl) aniline by condensation with glycidol, and then cyclization of the product obtained (IIId) with ethyl carbonate, according to the protocols described in French Patent No. 2,356,422 .

. Fusion point :. 1030C
. Gross formula: C16H23N03
Elemental analysis

<SEP> C <SEP> H <SEP> N
<tb> Calculated <SEP> (%) <SEP> 69.28 <SEP> 8.36 <SEP> 5.05
<tb> Found <SEP> (% <SEP> 69.58 <SEP> 8.53 <SEQ> 4.88
<tb> TABLE 1

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 235 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2COO- <SEP>#<SEP> C22H26N2O5 <SEP> 398.44 <SEP> 88 <SEP> 84 <SEP> Cal. <SEP> 66.31 <SEP> 6.58 <SEP> 7.03
<tb><SEP> Tr. <SEP> 66.28 <SEP> 6.73 <SEP> 6.90
<tb> 236 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C23H26N2C6 <SEP> 426.45 <SEP> 58 <SEP> 27 <SEP> Cal. <SEP> 64.47 <SEP> 6.15 <SEP> 6.57
<tb><SEP> Tr. <SEP> 64.47 <SEP> 6.32 <SEP> 6.49
<tb> 178 <SEP>"<SEP>"<SEP>"<SEP> CH2OCOCH2O- # <SEP>#<SEP> C25H22N2C8 <SEP> 478.44 <SEP> 20 <SEP> 64 <SEP> Cal. <MS> 62.76 <SEP> 4.64 <SEP> 5.85
<tb><SEP> Tr. <SEP> 62.89 <SEP> 4.66 <SEP> 5.84
<tb> 179 <SEP>"<SEP>"<SEP>"<SEP> CH2OCH3 <SEP>#<SEP> C15H19NO2 <SEP> 277.3 <SEP> 63 <SEP> 74 <SEP> Cal. <SEP> 6.96 <SEP> 6.91 <SEP> 5.05
<tb><SEP> Tr. <SEP> 64.67 <SEP> 6.71 <SEP> 4.97
<tb> TABLE I (SIE)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 180 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C3H18N2O3 <SEP> 250.29 <SEP> 92 <SEP> 59 <SEP> Cal. <SEP> 62.38 <SEP> 7.25 <SEP> 11.19
<tb><SEP> Tr. <SEP> 62.45 <SEP> 6.98 <SEP> 10.94
<tb> 181 <SEP>"<SEP>"<SEP>"<SEP> CH2OCH3 <SEP>#<SEP> C17H24N2O5 <SEP> 336.38 <SEP> 92 <SEP> 75 <SEP> Cal. <SEP> 60.70 <SEP> 7.19 <SEP> 8.33
<tb><SEP> Tr. <SEP> 60.47 <SEP> 7.04 <SEP> 8.10
<tb> 182 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C17H23NO5 <SEP> 321.36 <SEP> 77 <SEP> 22 <SEP> Cal. <SEP> 63.53 <SEP> 7.21 <SEP> 4.36
<tb><SEP> Tr. <SEP> 63.67 <SEP> 7.23 <SEP> 4.38
<tb> 183 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C16H21NO1 <SEP> 291.34 <SEP> 81 <SEP> 31 <SEP> Cal. <SEP> 65.96 <SEP> 7.27 <SEP> 4.81
<tb><SEP> Tr. <SEP> 66.00 <SEP> 7.46 <SEP> 4.71
<tb> TABLE I (continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 184 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C17H21NO4 <SEP> 303.35 <SEP> 83 <SEP> 33 <SEP> Cal. <SEP> 67.31 <SEP> 6.95 <SEP> 4.62
<tb><SEP> Tr. <SEP> 67.01 <SEP> 7.08 <SEP> 4.43
<tb> 185 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C16H21NO4 <SEP> 291.34 <SEP> 84 <SEP> 78 <SEP> Cal. <SEP> 65.96 <SEP> 7.27 <SEP> 4.81
<tb><SEP> Tr. <SEP> 66.03 <SEP> 7.28 <SEP> 4.59
<tb> 234 <SEP>"<SEP>"<SEP>"<SEP>"<SEP> O- (CH2) 4Cl <SEP> C15H20ClNO4 <SEP> 313.77 <SEP> 58 <SEP> 66 <SEP> Cal. <SEP> 57.41 <SEP> 6.42 <SEP> 4.46
<tb><SEP> Tr. <SEP> 57.05 <SEP> 6.50 <SEP> 4.50
<tb> 186 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C18H25NO4 <SEP> 319.39 <SEP> 77 <SEP> 22 <SEP> Cal. <SEP> 67.69 <SEP> 7.89 <SEP> 4.39
<tb><SEP> Tr. <SEP> 67.62 <SEP> 8.03 <SEP> 4.25
<tb> TABLE (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 237 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP> O (CH2) 3COCH3 <SEP> C16H21NO5 <SEP> 307.37 <SEP> 66 <SEP> 57 <SEP> Cal . <SEP> 62.52 <SEP> 6.89 <SEP> 4.56
<tb><SEP> Tr. <SEP> 62.36 <SEP> 6.88 <SEP> 4.50
<tb> 187 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H19NO3 <SEP> 309.35 <SEP> 166 <SEP> 26 <SEP> Cal. <SEP> 73.76 <SEP> 6.19 <SEP> 4.53
<tb><SEP> Tr. <SEP> 73.52 <SEP> 6.10 <SEP> 4.38
<tb> 238 <SEP>"<SEP>"<SEP>"<SEP>"<SEP> -O- (CH2) 2COCH3 <SEP> C15H19NO5 <SEP> 293.3 <SEP> 98 <SEP> 34 <SEP > Cal. <SEP> 61.42 <SEP> 6.53 <SEP> 4.78
<tb><SEP> Tr. <SEP> 61.70 <SEP> 6.59 <SEP> 4.70
<tb> 188 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C18H23NO5 <SEP> 333.37 <SEP> 102 <SEP> 70 <SEP> Cal. <SEP> 64.85 <SEP> 6.95 <SEP> 4.20
<tb><SEP> Tr. <SEP> 64.82 <SEP> 7.11 <SEP> 4.19
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 239 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C18H17N2O6 <SEP> 358.34 <SEP> 88 <SEP> 47 <SEP> Cal. <SEP> 60.33 <SEP> 5.06 <SEP> 7.82
<tb><SEP> Tr. <SEP> 60.49 <SEP> 5.14 <SEP> 7.76
<tb> 189 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H17NO3 <SEP> 307.33 <SEP> 120 <SEP> 50 <SEP> Cal. <SEP> 74.25 <SEP> 5.58 <SEP> 4.56
<tb><SEP> Tr. <SEP> 74.18 <SEP> 5.30 <SEP> 4.47
<tb> 190 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H18NO3Cl <SEP> 343.80 <SEP> 136 <SEP> 30 <SEP> Cal. <SEP> 66.37 <SEP> 5.28 <SEP> 4.07
<tb><SEP> Tr. <SEP> 66.08 <SEP> 5.24 <SEP> 3.96
<tb> 191 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H18N2O5 <SEP> 354.35 <SEP> 110 <SEP> 50 <SEP> Cal. <SEP> 64.40 <SEP> 5.12 <SEP> 7.91
<tb><SEP> Tr. <SEP> 64.17 <SEP> 5.24 <SEP> 7.96
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 192 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C19H21NO3 <SEP> 311.37 <SEP> 74 <SEP> 62 <SEP> Cal. <SEP> 73.29 <SEP> 6.80 <SEP> 4.50
<tb><SEP> Tr. <SEP> 73.17 <SEP> 6.93 <SEP> 4.58
<tb> 193 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H19NO3 <SEP> 309.35 <SEP> 82 <SEP> 60 <SEP> Cal. <SEP> 73.76 <SEP> 6.19 <SEP> 4.63
<tb><SEP> Tr. <SEP> 73.47 <SEP> 6.10 <SEP> 4.50
<tb> 194 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H18N2O5 <SEP> 354.35 <SEP> Oil <SEP> 40 <SEP> Cal. <SEP> 64.40 <SEP> 5.12 <SEP> 7.91
<tb><SEP> Tr. <SEP> 64.25 <SEP> 5.27 <SEP> 7.92
<tb> 195 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C17H17NO2 <SEP> 283.31 <SEP> 120 <SEP> 75 <SEP> Cal. <SEP> 72.06 <SEP> 6.05 <SEP> 4.91
<tb><SEP> Tr. <SEP> 72.27 <SEP> 5.91 <SEQ> 4.62
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 240 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C19H20N2O3 <SEP> 324.37 <SEP> 146 <SEP> 32 <SEP> Cal. <SEP> 70.35 <SEP> 6.22 <SEP> 8.61
<tb><SEP> Tr. <SEP> 70.22 <SEP> 6.26 <SEP> 8.70
<tb> 196 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C20H18N2O3 <SEP> 334.36 <SEP> 127 <SEP> 70 <SEP> Cal. <SEP> 71.84 <SEP> 5.43 <SEP> 8.38
<tb><SEP> Tr. <SEP> 71.89 <SEP> 5.36 <SEP> 8.43
<tb> 197 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C18H18BrNO4 <SEP> 392.24 <SEP> 116 <SEP> 81 <SEP> Cal. <SEP> 55.11 <SEP> 4.63 <SEP> 3.57
<tb><SEP> Tr. <SEP> 54.94 <SEP> 4.35 <SEP> 3.55
<tb> 241 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C20H12N2O5 <SEP> 370.39 <SEP> 198 <SEP> 80 <SEP> Cal. <SEP> 64.85 <SEP> 5.99 <SEP> 7.56
<tb><SEP> Tr. <SEP> 64.80 <SEQ> 5.69 <SEP> 7.29
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 242 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C18H20N2O4 <SEP> 328.36 <SEP> 168 <SEP> 69 <SEP> Cal. <SEP> 65.84 <SEP> 6.14 <SEP> 8.53
<tb><SEP> Tr. <SEP> 65.55 <SEP> 6.46 <SEP> 8.47
<tb> 243 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H22N2O6S <SEP> 406.45 <SEP> 142 <SEP> 59 <SEP> Cal. <SEP> 56.14 <SEP> 5.46 <SEP> 6.89
<tb><SEP> Tr. <SEP> 56.34 <SEP> 5.56 <SEP> 6.91
<tb> 244 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C21H24N2O5 <SEP> 388.92 <SEP> 116 <SEP> 84 <SEP> Cal. <SEP> 64.85 <SEP> 6.35 <SEP> 7.20
<tb><SEP> + <SEP> 1/4 <SEP> H20 <SEP> Tr. <SEP> 64.65 <SEP> 6.65 <SE> 6.83
<tb> 198 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C30H18NIO1 <SEP> 439.24 <SEP> 118 <SEP> 78 <SEP> Cal. <SEP> 49.22 <SEP> 4.13 <SEP> 3.19
<tb><SEP> Tr. <SEP> 49.39 <SE> 4.08 <SEP> 3.13
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP>[&alpha;] D20 <SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
## EQU1 ## <SEP> 55.20 <SEP> 4.39 <SEP> 3.39
<tb><SEP> Tr. <SEP> 55.50 <SEP> 4.43 <SEP> 3.49
### <SEP> 64.03 <SEP> 5.66 <SEP> 7.86
<tb><SEP> Tr. <SEP> 63.78 <SEP> 5.64 <SEP> 7.79
<tb> 199 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C.9H18N2O4 <SEP> 338.35 <SEP> 83 <SEP> 75 <SEP> Cal. <SEP> 67.44 <SEP> 5.36 <SEP> 6.28
<tb><SEP>[&alpha;] d20-39.7 <SEP> Tr. <SEP> 67.14 <SEP> 5.53 <SEP> 6.38
<tb><SEP> (C = 1 / CH2Cl2)
<tb> 200 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H18N2O4 <SEP> 338.35 <SEP> 84 <SEP> 51 <SEP> Cal. <SEP> 67.44 <SEP> 5.36 <SEP> 8.28
<tb><SEP>[&alpha;] d20 + 38.7 <SEP> Tr. <SEP> 67.52 <SEP> 5.36 <SEP> 8.28
<tb><SEP> (C = 1 / CH2Cl2)
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb><SEP> 4.48
<tb> 247 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C18H16D2N2O6 <SEP> 360.35 <SEP> 99 <SEP> 55 <SEP> Cal. <SEP> 59.99 <SEP> +1.12 <SEP> 7.78
<tb><SEP> Tr. <SEP> 59.94 <SEP> 5.17 <SEP> 7.57
### <SEP> 62.32 <SEP> 6.02 <SEP> 10.90
<tb><SEP> Tr. <SEP> 62.04 <SEP> 5.90 <SEP> 10.75
<tb> 202 <SEP>"<SEP>"<SEP>"<SEP> CH2-N # O <SEP>"<SEP> C21H23N3O6 <SEP> 413.42 <SEP> 138 <SEP> 26 <SEP> Cal . <SEP> 61.0 <SEP> 5.61 <SEP> 10.17
<tb><SEP> Tr. <SEP> 61, @@ <SEP> 5.67 <SEP> 10.01
<tb> 203 <SEP>"<SEP>"<SEP>"<SEP> CH2-NH-And <SEP>"<SEP> C19H21N3O5 <SEP> 317.38 <SEP> 70 <SEP> 54 <SEP> Cal . <SEP> 61.44 <SEP> 5.70 <SEP> 11.32
<tb><SEP> Tr. <SEP> 61.48 <SEP> 5.58 <SEP> 11.57
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 204 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2- # <SEP>#<SEP> C2H23N3O5 <SEP> 397.42 <SEP> 110 <SEP> 24 <SEP> Cal. <SEP> 63.46 <SEP> 5.83 <SEP> 10.57
<tb><SEP> Tr. <SEP> 63.16 <SEP> 5.90 <SEP> 10.39
<tb> 205 <SEP>"<SEP>"<SEP>"<SEP> CH2-NH2 <SEP>#<SEP> C18H17N3O3 <SEP> 323.34 <SEP> 94 <SEP> 10 <SEP> Cal. <SEP> 66.86 <SEP> 5.30 <SEP> 13.00
<tb><SEP> Tr. <SEP> 66.73 <SEP> 5.58 <SEP> 12.69
<tb> 206 <SEP>"<SEP>"<SEP>"<SEP> CH2-N # <SEP>"<SEP> C20H21N3O3 <SEP> 351.39 <SEP> 84 <SEP> 62 <SEP> Cal. <SEP> 68.36 <SEP> 6.02 <SEP> 11.96
<tb><SEP> Tr. <SEP> 68.38 <SEP> 6.30 <SEP> 11.69
<tb> 207 <SEP>"<SEP>"<SEP>"<SEP> CH2NH2 <SEP>#<SEP> C17H16CIN3O5 <SEP> 475.06 <SEP> 155 <SEP> 11 <SEP> Cal. <SEP> 54.04 <SEP> 4.27 <SEP> 11.12
<tb><SEP> Tr. <SEP> 54.17 <SEP> 4.31 <SEP> 11.26
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

TABLEAU I (Suite)

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 248 <SEP> 0 <SEP> 0 <SEP> H <SEP>#<SEP>#<SEP> C19H20N2O7 <SEP> 388.37 <SEP> 118 <SEP> 50 <SEP> Cal. <SEP> 58.76 <SEP> 5.19 <SEP> 7.21
<tb><SEP> Tr. <SEP> 58.64 <SEP> 5.01 <SEP> 7.37
<tb> 249 <SEP>"<SEP>"<SEP>"<SEP>#<SEP>#<SEP> C21H24CINO5 <SEP> 405.87 <SEP> Oil <SEP> 73 <SEP> Cal. <SEP> 62.14 <SEP> 5.96 <SEP> 3.45
<tb><SEP> Tr. <SEP> 61.96 <SEP> 5.79 <SE> 3.37
<tb> 250 <SEP>"<SEP>"<SEP>"<SEP>#<SEP>#<SEP> C16H23NO5 <SEP> 309.35 <SEP> 63 <SEP> 41 <SEP> Cal. <SEP> 62.12 <SEP> 7.49 <SEP> 4.59
<tb><SEP> Tr. <SEP> 62.14 <SEP> 7.23 <SEP> 4.29
<tb> 251 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C18H25NO5 <SEP> 335.39 <SEP> 84 <SEP> 27 <SEP> Cal. <SEP> 64.46 <SEP> 7.51 <SEP> 4.18
<tb><SEP> Tr. <SEP> 64.37 <SEP> 7.63 <SEP> 4.06
<Tb>

TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 252 <SEP> 0 <SEP> 0 <SEP> H <SEP>#<SEP>#<SEP> C20H20N2O5 <SEP> 368.38 <SEP> 96 <SEP> 44 <SEP> Cal. <SEP> 65.21 <SEP> 5.47 <SEP> 7.61
<tb><SEP> Tr. <SEP> 64.94 <SEP> 5.50 <SEP> 7.93
<tb> 253 <SEP>"<SEP>"<SEP>"<SEP>#<SEP>#<SEP> C19H18N2O7 <SEP> 386.35 <SEP> 87 <SEP> 17 <SEP> Cal. <SEP> 59.06 <SEP> 4.70 <SEP> 7.25
<tb><SEP> Tr. <SEP> 58.64 <SEP> 4.79 <SEP> 7.17
<tb> 254 <SEP>"<SEP>"<SEP>"<SEP>#<SEP>#<SEP> C15H18N2O5 <SEP> 306.3 @ <SEP> 92 <SEP> 25 <SEP> Cal. <SEP > 58.81 <SEP> 5.92 <SEP> 9.15
<tb><SEP> Tr. <SEP> 58.84 <SEP> 5.96 <SEP> 9.32
<tb> 255 <SEP>"<SEP>"<SEP>"<SEP>#<SEP>#<SEP> C18H18N2O6 <SEP> 358.34 <SEP> 134 <SEP> 18 <SEP> Cal. <SEP> 60.33 <SEP> 5.06 <SEP> 7.82
<tb><SEP> Tr. <SEP> 60.21 <SEP> 4.92 <SEP> 7.83
<tb> * <SEP> couple <SEP> of <SEP> diastereoisomers <SEP> erytbro
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 256 ** <SEP> 0 <SEP> 0 <SEP> H <SEP>#<SEP>#<SEP> C18H18N2O6 <SEP> 358.34 <SEP> 127 <SEP> 21 <SEP> Cal. <SEP> 60.33 <SEP> 5.06 <SEP> 7.82
<tb><SEP> Tr. <SEP> 60.50 <SEP> 5.15 <SEP> 7.84
<tb> 257 <SEP>"<SEP>"<SEP>"<SEP> -COCH3 <SEP>"<SEP> C18H16N2O6 <SEP> 356.32 <SEP> 107 <SEP> 37 <SEP> Cal. <SEP> 60.67 <SEP> 4.53 <SEP> 7.86
<tb><SEP> Tr. <SEP> 60.90 <SEQ> 4.29 <SEP> 7.74
<tb> 258 * <SEP>"<SEP>"<SEP>"<SEP>#<SEP>"<SEP> C19H20N2O6 <SEP> 372.37 <SEP> 92 <SEP> 25 <SEP> Cal. <SEP> 61.28 <SEP> 5.41 <SEP> 7.52
<tb><SEP> Tr. <SEP> 61.24 <SEP> 5.52 <SEP> 7.58
<tb> 259 ** <SEP>"<SEP>"<SEP>"<SEP>#<SEP>"<SEP>"<SEP>"<SEP> 107 <SEP> 21 <SEP> Cal. <SEP> 61.28 <SEP> 5.41 <SEP> 7.52
<tb><SEP> Tr. <SEP> 61.44 <SEP> 5.36 <SEP> 7.60
<tb> * couple of diastereomers erytaro ** couple of diastereoisomers tbréo TABLE I

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 208 <SEP> 8 <SEP> 0 <SEP> H <SEP> CH2OCOEt <SEP>#<SEP> C20H20N2O6S <SEP> 416.44 <SE> 126 <SEP> 73 <SEP> Cal. <SEP> 57.68 <SEP> 4.84 <SEP> 6.73
<tb><SEP> Tr. <SEP> 57.59 <SEP> 5.03 <SEP> 6.69
<tb> 209 <SEP>"<SEP>"<SEP>"<SEP> CH2ON <SEP>#<SEP> C18H15PN2O5S <SEP> 358.38 <SEP> 126 <SEP> 27 <SEP> Cal. <SEP> 59.57 <SEP> 4.31 <SEP> 7.72
<tb><SEP> Tr. <SEP> 59.72 <SEP> 4.52 <SEP> 7.54
<tb> 210 <SEP>"<SEP>"<SEP>"<SEP> CH2OC3H7n <SEP>#<SEP> C20H22N2O5S <SEP> 402.46 <SEP> 110 <SEP> 57 <SEP> Cal. <SEP> 59.68 <SEP> 5.51 <SEP> 6.96
<tb><SEP> Tr. <SEP> 59.57 <SEP> 5.65 <SEP> 7.19
<tb> 211 <SEP>"<SEP>"<SEP>"<SEP> CH2OCH3 <SEP>#<SEP> C17H23NO3S <SEP> 321.43 <SEP> 68 <SEP> 35 <SEP> Cal. <SEP> 63.52 <SEP> 7.21 <SEP> 4.36
<tb><SEP> Tr. <SEP> 63.61 <SEP> 7.43 <SEP> 4.33
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 212 <SEP> 8 <SEP> 0 <SEP> H <SEP> CH2CH <SEP> O-CH2) 3-CN <SEP> C19H16N2O3S <SEP> 292.35 <SEP> 80 <SEQ> 54 <SEP > Cal. <SEP> 57.51 <SEP> 5.52 <SEP> 9.58
<tb><SEP> Tr. <SEP> 57.40 <SEP> 5.32 <SEP> 9.42
<tb> 213 <SEP>"<SEP>"<SEP>"<SEP> CH2OCH3 <SEP>#<SEP> C17H18N2O3S <SEQ> 460.95 <SEP> 133 <SEP> 17 <SEP> Cal. <SEP> 51.85 <SEP> 4.57 <SEP> 6.08
<tb><SEP> Tr. <SEP> 51.68 <SEP> 4.40 <SEP> 6.04
<tb> 214 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C16H33NO3S <SEP> 309.42 <SEP> Oil <SEP> 30 <SEP> Cal. <SEP> 62.10 <SEP> 7.49 <SEP> 4.53
<tb><SEP> Tr. <SEP> 62.41 <SEP> 7.61 <SEP> 4.45
<tb> 215 <SEP>"<SEP>"<SEP>"<SEP> CH2OH <SEP> O- (CH2) 4-ON <SEP> C15H18N2O3S <SEP> 306.37 <SEP> 106 <SEP> 40 <MS> Cal. <SEP> 58.80 <SEP> 5.92 <SEP> 9.14
<tb><SEP> Tr. <SEP> 58.88 <SEP> 5.71 <SEP> 9.12
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 216 <SEP> 8 <SEP> 0 <SEP> H <SEP> CH2OEt <SEP>#<SEP> C19H20N2O5S <SEP> 388.43 <SEP> 80 <SEP> 47 <SEP> Cal. <SEP> 58.75 <SEP> 5.19 <SEP> 7.21
<tb><SEP> Tr. <SEP> 58.68 <SEP> 5.09 <SEP> 7.28
<tb> 217 <SEP>"<SEP>"<SEP>"CH2OCH3<SEP> -O- (CH2) 4-ON <SEP> C16H20N2O3S <SEP> 320.40 <SEP> Oil <SEP> 24 <SEP> Cal <SEP> 59.97 <SEP> 6.29 <SEP> 8.74
<tb><SEP> Tr. <SEP> 59.87 <SEP> 6.28 <SEP> 9.02
<tb> 218 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H17N3O5S <SEP> 399.42 <SEP> 176 <SEP> 57 <SEP> Cal. <SEP> 37.15 <SEP> 4.29 <SEP> 10.52
<tb><SEP> Tr. <SEP> 57.06 <SEP> 4.19 <SEP> 10.46
<tb> 219 <SEP> 0 <SEP> 8 <SEP>"<SEP>"<SEP>#<SEP> C18H18N2O5S <SEP> 374.41 <SEP> 74 <SEP> 47 <SEP> Cal. <SEP> 57.74 <SEP> 4.85 <SEP> 7.48
<tb><SEP> Tr. <SEP> 57.45 <SEP> 4.97 <SEP> 7.18
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 220 <SEP> H3 <SEP> CH2 <SEP> H <SEP> CH2OH <SEP>#<SEP> C18H21NO2 <SEP> 283.36 <SEP> 87 <SEP> 85 <SEP> Cal. <SEP> 76.29 <SEP> 7.47 <SEP> 4.94
<tb><SEP> Tr. <SEP> 76.40 <SEP> 7.60 <SEP> 4.65
<tb> 260 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C14H18N2O5 <SEP> 294.30 <SEP> 115 <SEP> 57 <SEP> Cal. <SEP> 57.13 <SEP> 6.17 <SEP> 9.52
<tb><SEP> Tr. <SEP> 57.09 <SEP> 6.19 <SEP> 9.51
<tb> 261 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H16N2O5 <SEP> 352.33 <SEP> 111 <SEP> 30 <SEP> Cal. <SEP> 64.77 <SEP> 4.58 <SEP> 7.95
<tb><SEP> Tr. <SEP> 64.94 <SEP> 4.64 <SEP> 7.92
<tb> 262 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H16NCIO3 <SEP> 341.78 <SEP> 83 <SEP> 45 <SEP> Cal.

<SEP> 66.76 <SEP> 4.72 <SEP> 4.10
<tb><SEP> Tr. <SEP> 66.60 <SEP> 4.66 <SEP> 4.03
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 263 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C19H20N2O6 <SEP> 372.37 <SEP> 68 <SEP> 22 <SEP> Cal. <SEP> 61.28 <SEP> 5.41 <SEP> 7.52
<tb><SEP> Tr. <SEP> 61,26 <SEP> 5,11 <SEP> 7,59
<tb> 264 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H20CINC4 <SEP> 361.81 <SEP> 50 <SEP> 19 <SEP> Cal. <SEP> 63.07 <SEP> 5.57 <SEP> 3.87
<tb><SEP> Tr. <SEP> 63.37 <SEP> 5.57 <SEP> 3.63
<tb> 265 * <SEP>"<SEP>"<SEP>"<SEP>#<SEP>#<SEP> C19H21NO4 <SEP> 327.37 <SEP> 83 <SEP> 66 <SEP> Cal. <SEP > 69.70 <SEP> 6.47 <SEP> 4.23
<tb><SEP> Tr. <SEP> 69.92 <SEP> 6.47 <SEP> 4.20
<tb> 266 * <SEP>"<SEP>"<SEP>"<SEP>#<SEP>#<SEP> C20H20N2O4 <SEP> 352.36 <SEP> 96 <SEP> 81 <SEP> Cal. <SEP > 68.17 <SEP> 5.72 <SEP> 7.95
<tb><SEP> Tr. <SEP> 67.88 <SEP> 5.67 <SEP> 7.96
<tb> * couple of Iastereoisomers erychro TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 267 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C20H20N2O4 <SEP> 352.38 <SEP> 60 <SEP> 32 <SEP> Cal. <SEP> 68.17 <SEP> 5.72 <SEP> 7.95
<tb><SEP> Tr. <SEP> 68.06 <SEP> 3.76 <SEP> 8.05
<tb> 268 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H16CINO3 <SEP> 341.78 <SEP> 152 <SEP> 21 <SEP> Cal. <SEP> 66.76 <SEP> 4.72 <SEP> 4.10
<tb><SEP> Tr. <SEP> 66.75 <SEP> 4.63 <SEP> 4.05
<tb> 269 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C17H16CINO3 <SEP> 317.76 <SEP> 140 <SEP> 69 <SEP> Cal. <SEP> 64.25 <SEP> 5.08 <SEP> 4.41
<tb><SEP> Tr. <SEP> 64.00 <SE> 4.90 <SEP> 4.36
<tb> 270 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C20H18N2O3 <SEP> 350.36 <SEP> 92 <SEP> 60 <SEP> Cal. <SEP> 68.56 <SEP> 5.18 <SEP> 8.00
<tb><SEP> Tr. <SEP> 68.46 <SEP> 5.15 <SEP> 7.78
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 271 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C19H20CINO3 <SEP> 345.81 <SEP> 62 <SEP> 37 <SEP> Cal. <SEP> 65.99 <SEP> 5.83 <SEP> 4.05
<tb><SEP> Tr. <SEP> 66.14 <SEP> 5.85 <SEP> 4.09
<tb> 272 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C20H20N2O3 <SEP> 336.38 <SEP> 102 <SEP> 40 <SEP> Cal. <SEP> 71.41 <SEP> 5.99 <SEP> 6.33
<tb><SEP> Tr. <SEP> 71.51 <SEP> 5.90 <SEP> 8.37
<tb> 273 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C18H18CINO4 <SEP> 347.79 <SEP> 82 <SEP> 22 <SEP> Cal. <SEP> 62.16 <SEP> 5.22 <SEP> 4.03
<tb><SEP> Tr. <SEP> 62.22 <SEP> 5.26 <SEP> 4.01
<tb> 274 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H18CINO4 <SEP> 359.80 <SEP> 50 <SEP> 82 <SEP> Cal. <SEP> 63.42 <SEP> 5.04 <SEP> 3.89
<tb><SEP> Tr. <SEP> 63.30 <SEP> 4.96 <SEP> 3.95
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 275 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C19H18N2O4 <SEP> 338.35 <SEP> 84 <SEP> 59 <SEP> Cal. <SEP> 67.44 <SEP> 5.36 <SEP> 8.28
<tb><SEP> Tr. <SEP> 67.45 <SEP> 5.23 <SEP> 8.29
<tb> 276 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C17H16N2O5 <SEP> 328.31 <SEP> 118 <SEP> 59 <SEP> Cal. <SEP> 62.19 <SEP> 4.91 <SEP> 8.53
<tb><SEP> Tr. <SEP> 62.42 <SEP> 4.95 <SEP> 8.52
<tb> 277 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H16CINO3 <SEP> 341.78 <SEP> 120 <SEP> 27 <SEP> Cal. <SEP> 66.76 <SEP> 4.72 <SEP> 4.10
<tb><SEP> Tr. <SEP> 66.13 <SEP> 4.59 <SEP> 4.33
<tb> 278 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C17H16CINO3 <SEP> 317.76 <SEP> 68 <SEP> 62 <SEP> Cal. <SEP> 64.25 <SEP> 5.08 <SEP> 4.41
<tb><SEP> Tr. <SEP> 64.07 <SEP> 5.00 <SEQ> 4.42
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 279 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C19H20N2O5 <SEP> 356.37 <SEP> 86 <SEP> 60 <SEP> Cal. <SEP> 64.03 <SEP> 5.66 <SEP> 7.86
<tb><SEP> Tr. <SEP> 64.15 <SEP> 5.61 <SEP> 7.82
<tb> 280 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C17H21NO3 <SEP> 287.35 <SEP><50<SEP> 28 <SEP> Cal. <SEP> 71.05 <SEP> 7.37 <SEQ> 4.87
<tb><SEP> Tr. <SEP> 70.95 <SEP> 7,16 <SEP> 5,11
<tb> 281 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C19H23NO3 <SEP> 312.38 <SEP> 86 <SEP> 18 <SEP> Cal. <SEP> 72.82 <SEP> 7.40 <SEP> 4.47
<tb><SEP> Tr. <SEP> 72.54 <SEP> 7.73 <SEP> 4.56
<tb> 282 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C20H16N2O3 <SEP> 332.34 <SEP> 98 <SEP> 25 <SEP> Cal. <SEP> 72.27 <SEP> 4.85 <SEP> 8.43
<tb><SEP> Tr. <SEP> 72.34 <SEP> 4.72 <SEP> 8.53
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 283 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C19H18N2O6 <SEP> 370.35 <SEP> 120 <SEP> 5 <SEP> Cal. <SEP> 61.61 <SEP> 4.90 <SEP> 7.56
<tb><SEP> Tr. <SEP> 61.45 <SEP> 4.96 <SEP> 7.40
<tb> 284 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C18H16N2O3 <SEP> 308.32 <SEP> 70 <SEP> 50 <SEP> Cal. <SEP> 70.1 @ <SEP> 5.23 <SEP> 9.09
<tb><SEP> Tr. <SEP> 69.90 <SEP> 5,12 <SEP> 8.92
<tb> 285 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C16H17N3O4 <SEP> 315.320 <SEP> 137 <SEP> 86 <SEP> Cal. <SEP> 60.94 <SEP> 5.43 <SEP> 13.33
<tb><SEP> Tr. <SEP> 60.69 <SE> 5.37 <SE> 13.13
<tb> 286 <SEP>"<SEP>"<SEP>"<SEP>"<SEP>#<SEP> C17H18N2O4 <SEP> 314,330 <SEP> 70 <SEP> 53 <SEP> Cal. <SEP> 64.95 <SEP> 5.77 <SEP> 8.91
<tb><SEP> Tr. <SEP> 64.88 <SEP> 5.72 <SEP> 8.82
<tb> TABLE I (Continued)

NO.
<Tb>

of <SEP> Point <SEP> Point <SEP> Rende- <SEP> AMALYBE <SEP> HTENRMEAITH.
<Tb>

sode <SEP> X <SEP> A <SEP> R1 <SEP> R2 <SEP> R <SEP> Raw <SEP> Formula <SEP> mplecu- <SEP> of <SEP> mant <SEP>% <SEP> C <SEP> H <SEP> N
<tb><SEP> lsire <SEP> merge
<tb><SEP> (C) <SEP> (%)
<tb> 287 <SEP> 0 <SEP> 0 <SEP> H <SEP> CH2OCH3 <SEP>#<SEP> C18H19NO3 <SEP> 297,340 <SEP> 67 <SEP> 97 <SEP> Cal. <SEP> 72.70 <SEP> 6.44 <SEP> 4.71
<tb><SEP> Tr. <SEP> 72.57 <SEP> 6.50 <SEP> 4.88
### Cal. <SEP> 70.07 <SEP> 8.65 <SE> 4.81
<tb><SEP> Tr. <SEP> 70.21 <SEP> 8.87 <SEP> 4.75
<tb><SEP> Cal.
<Tb>

<SEP> Tr.
<Tb>

<SEP> Cal.
<Tb>

<SEP> Tr.
<Tb>

 The compounds of formula (I) have been studied in laboratory animals and have shown activities in the psychotropic field as potential antidepressants.

These activities are highlighted in the following tests
Test A: potentiation in the mouse of generalized tremor caused by an intraperitoneal injection (200 mg / kg) of dl-5-hydroxytryptophan, according to the protocol described by GOURET C. and RAYNAUD
G, in J. Pharmacol. (Paris) (1974), 5, 231.

 Test B: antagonism against ptosis observed one hour after an intravenous injection (2 mg / kg) of reserpine in the mouse according to the protocol described by GOURET C. and THOMAS J. in J. Pharmacol.

(Paris), (1973), ks 401.

The results of these two tests as well as those of a reference substance, TOLOXATONE, are summarized in Table II below.
TABLE II

<tb> Compound <SEP> tested <SEP> Test <SEP> A <SEP> Test <SEP> B <SEP> Toxicity <SEP> (mouse)
<tb> N <SEP> of <SEP> code <SEP> DE50 <SEP> (mg / kg.in) <SEP> DE50 <SEP> (mg / kg / po) <SEP> LD50 <SEP> (mg / kg) kg / in)
<tb><SEP> 178 <SEP> 33 <SEP> 28 <SEP>> 1 <SEP> 000 <SEP>
<tb><SEP> 179 <SEP> 4.5 <SEP> 7
<tb><SEP> 180 <SEP> 7.4 <SEP> 7.8 <SEP> 1 <SEP> ooo <SEP> (20%)
<tb><SEP> 181 <SEP> 4 <SEP> 9 <SEP>> 2 <SEP> 000
<tb><SEP> 182 <SEP> 3.7 <SEP> 5.8
<tb><SEP> 183 <SEP> 1,9 <SEP> 2,4
<tb><SEP> 184 <SEP> 1.2 <SEP> 0.72
<tb><SEP> 185 <SEP> 12 <SEP> 7
<tb><SEP> 186 <SEP> 3 <SEP> 3
<tb><SEP> 187 <SEP> 2.7 <SEP> 1.3 <SEP>
<tb><SEP> 188 <SEP> 0.3 <SEP> 0.4
<tb><SEP> 189 <SEP> 2.6 <SEP> 0.9
<tb><SEP> 190 <SEP> 1 <SEP> 0.23 <SEP> 7 <SEP> 2 <SEP> 000
<tb><SEP> 191 <SEP> 0.4 <SEP> 0.38 <SEP> 1 <SEP> 000 <SEP> (40%)
<tb><SEP> 192 <SEP> 5.8 <SEP> 6 <SEP>> 1000 <SEP>
<tb><SEP> 193 <SEP> 19 <SEP> 30
<tb><SEP> 194 <SEP> 6.4 <SEP> 5.8
<tb><SEP> 195 <SEP> 1,2 <SEP> 2,2 <SEP>> 1 <SEP> 000
<tb><SEP> 196 <SEP> - <SEP> 0.55
<tb><SEP> 197 <SEP> 2.2 <SEP> 6.7
<tb><SEP> 198 <SEP> 40 <SEP> 34
<tb><SEP> 199 <SEP> 0.31
<tb><SEP> 200 <SEP> 1.7
<tb><SEP> 201 <SEP> 7.4 <SEP> 6.8
<tb><SEP> 202 <SEP> 10 <SEP> 10
<tb><SEP> 203 <SEP> 5.2 <SEP> 1.4 <SEP> 1 <SEP> ooo <SEP> (4%) <SEP>
<tb><SEP> 204 <SEP> 50 <SEP> 40 <SEP> 1 <SEP> ooo <SEP> (4%) <SEP>
<tb><SEP> 205 <SEP> 10.1 <SEP> 3 <SEP>> 1 <SEP> 000
<tb><SEP> 206 <SEP> 6 <SEP> 4.3
<tb><SEP> 207 <SEP> 9.1 <SEP> 7.6
<tb><SEP> 208 <SEP> 10 <SEP> 4.2
<tb><SEP> 209 <SEP> 7 <SEP> 6.7 <SEP> 1 <SEP> ooo <SEP> (20%)
<tb><SEP> 210 <SEP> 26 <SEP> 7.4 <SEP>? 1 <SEP> 000
<tb><SEP> 211 <SEP> 2 <SEP> 1,2 <SEP> 1 <SEP> ooo <SEP> (20%)
<Tb>
TABLE II (continued)

<tb> Compound <SEP> tested <SEP> Test <SEP> A <SEP> Test <SEP> B <SEP> Toxicity <SEP> (mouse)
<tb><SEP> n <SEP> of <SEP> code <SEP> DE50 <SEP> (mg / kg / in) <SEP> DE50 <SEP> (mg / kg / in) <SEP> LD50 <SEP> (mg / kg / in)
<tb><SEP> 212 <SEP> 4.3 <SEP> 12
<tb><SEP> 213 <SEP> 3 <SEP> 2 <SEP> 1 <SEP> 000 <SEP> (100%) <SEP>
<tb><SEP> 214 <SEP> 0.84 <SEP> 1.8 <SEP> 1 <SEP> 000 <SEP> (40%)
<tb><SEP> 215 <SEP> 6.2 <SEP> 10 <SEP>><SEP> 1 <SEP> 000
<tb><SEP> 216 <SEP> 5 <SEP> 3 <SEP> 1 <SEP> ooo <SEP> (80%) <SEP>
<tb><SEP> 217 <SEP> 1 <SEP> 1
<tb><SEP> 218 <SEP> 7.2 <SEP> 13.5 <SEP>> 1 <SEP> 000 <SEP>
<tb><SEP> 219 <SEP> 7 <SEP> 13.5
<tb><SEP> 220 <SEP> 50 <SEP> 50
<tb><SEP> 234 <SEP> o, 6 <SEP> 4 <SEP>><SEP> 1 <SEP> 000
<tb><SEP> 235 <SEP> 7.2 <SEP> 6.4 <SEP>><SEP> 1 <SEP> 000 <SEP>
<tb><SEP> 236 <SEP> 12.5 <SEP> 10
<tb><SEP> 237 <SEP> 10 <SEP> 10
<tb><SEP> 238 <SEP> 1,9 <SEP> 1,1
<tb><SEP> 239 <SEP> 1.6 <SEP> 1.1
<tb><SEP> 240 <SEP> 1.9 <SEP> 1.5
<tb><SEP> 241 <SEP> 4.6 <SEP> 5.6
<tb><SEP> 242 <SEP> 4.7 <SEP> 1.9
<tb><SEP> 243 <SEP> 12.5 <SEP> 4.5
<tb><SEP> 244 <SEP> 2.1 <SEP> 4 <SEP> 800
<tb><SEP> 245 <SEP> 12.5 <SEP> 13 <SEP>? <SEP> 1 <SEP> 000 <SEP>
<tb><SEP> 246 <SEP> 1.4 <SEP> 2.2
<tb><SEP> 247 <SEP> 0.1 <SEP> 0.1
<tb><SEP> 248 <SEP> 4.5 <SEP> 5.1
<tb><SEP> 249 <SEP> 42 <SEP> 20
<tb><SEP> 250 <SEP> 19.5 <SEP> 16.5
<tb><SEP> 251 <SEP> 9 <SEP> 9.6 <SEP>> 1 <SEP> 000
<tb><SEP> 252 <SEP> 6.6 <SEP> 6.5
<tb><SEP> 253 <SEP> 5 <SEP> 5.2 <SEP>><SEP> 1 <SEP> 000 <SEP>
<tb><SEP> 254 <SEP> 10 <SEP> 7.5
<tb><SEP> 255 <SEP> 2.7 <SEP> 1.5
<tb><SEP> 256 <SEP> 9.2 <SEP> a, 8 <SEP>
<tb><SEP> 257 <SEP> 6.2 <SEQ> 3.7
<Tb>
TABLE II (continued)

<tb> Compound <SEP> tested <SEP> Test <SEP> A <SEP> Test <SEP> B <SEP> Toxicity <SEP> (mouse)
<tb><SEP> N <SEP> of <SEP> code <SEP> DE50 <SEP> (mg / kg / in) <SEP> DE50 <SEP> (mg / kg / in) <SEP> tL50 <SEP> (mg / kg / in)
<tb><SEP> 258 <SEP> 0.5 <SEP> 0.4
<tb><SEP> 259 <SEP> 29 <SEP> 19.5
<tb><SEP> 260 <SEP> 4.8 <SEP> 4 <SEP> 1 <SEP> ooo <SEP> (20%)
<tb><SEP> 261 <SEP> 0.5 <SEP> 0.4
<tb><SEP> 262 <SEP> 14 <SEP> 20
<tb><SEP> 263 <SEP> 2.5 <SEP> 2,4
<tb><SEP> 264 <SEP> 2,8 <SEP> 3
<tb><SEP> 265 <SEP> 12.5 <SEP> 14
<tb><SEP> 266 <SEP> 1.5 <SEP> 0.7
<tb><SEP> 267 <SEP> 1.8 <SEP> 1.3
<tb><SEP> 268 <SEP> 35 <SEP> 10
<tb><SEP> 269 <SEP> 1.7 <SEP> 1,2
<tb><SEP> 270 <SEP> 0.2 <SEP> 0.2
<tb><SEP> 271 <SEP> 4.1 <SEP> 3.8
<tb><SEP> 272 <SEP> 0.5 <SEP> 0.4
<tb><SEP> 273 <SEP> 5.9 <SEP> 3,4
<tb><SEP> 274 <SEP> 1.2 <SEP> 0.9
<tb><SEP> 275 <SEP> 0.6 <SEP> 0.3
<tb><SEP> 276 <SEP> 11.7 <SEP> 18
<tb><SEP> 277 <SEP> 1.2 <SEP> 1.7
<tb><SEP> 278 <SEP> 11 <SEP> 11.5
<tb><SEP> 279 <SEP> 0.5 <SEP> 0.6
<tb><SEP> 280 <SEP> 1.5 <SEP> 3
<tb><SEP> 281 <SEP> 1.3 <SEP> 0.6
<tb><SEP> 282 <SEP> 0.3 <SEP> 0.3
<tb><SEP> 283 <SEP> 0.4 <SEP> 0.3
<tb><SEP> 284 <SEP> 1,2 <SEP> 1,3
<tb><SEP> 285 <SEP><10
<tb><SEP> 286 <SEP><10
<tb> TOLOXATONE <SEP> 60 <SEP> 50
<Tb>
It will be seen from the results listed in Table II that the compounds according to the invention are far more active than TOLOXATONE, a known reference compound.

The compounds which are the subject of the present application are indicated for the treatment of endogenous and exogenous depressive states and will be administered
- Orally in the form of tablets, dragees or capsules, at a dosage of 50 to 500 mg / day on average active prineipe.

 - In the form of injectable solution, at a dosage of 5 to 50 mg / day of active ingredient; the solvent used consists of binary or ternary mixtures containing, for example, water, polypropylene glycol, polyethylene glycol 300 or 400, or any other physiological solvent, the relative proportions of the various constituents being adjusted as a function of the dose administered.

Claims (21)

 1. New N-aryl azolones, characterized in that they correspond to the formula

 in which the set (X, A, R1) takes any one of the following values  a) (S, O, H), in which case R2 represents  or an ester group of formula -CH2-OCOEt and R denotes  the metanitrobenzyloxy group,  - the hydroxymethyl group and R then designates the group  (3-cyano-4-fluoro) benzyloxy, (3-cyano) propoxy or (4-cyano)  butoxy,  - the methoxymethyl group and R then represents the group  (3-cyano-5-nitro) benzyloxy, (3-pyridyl) methyloxy. (3-methyl)  butoxy, cyclopentylmethyloxy or (cyano-4) butoxy,  - an ethoxymethyl or n-propoxymethyl group and R denotes  then the metanitrobenzyloxy group  b) (O, S, H), in which case R2 represents the methoxymethyl group and  R then refers to the metanitrobenzyloxy group;  c) (H2, CR2, H), in which case R2 represents the hydroxymethyl group  and R denotes then the benzyloxy group;  d) (O, O, ii), in which case R2 represents  or an ester group of formula -CH2-OCO-CH2-O-C6H5 and R  then denotes the metanitrobenzyloxy group, - is an ester group of formula -CH2-OCO-C4Hg (t) and R denotes  then the para aminobenzyloxy or para formylaminobenzy group  loxy, - is a mehoxymethyl group and R is then:  dimethylamino group, a substituted or unsubstituted phenyl group of formula

 in which R 3 = H, 3-Cl, 4-Cl, 3-NO 2 or 3-CN, the benzyl group, a styryl group of trans configuration, of formula

 in which R4 = H, Cl, NH2, CN or NO2, the styryl or metanitrostyryl group, of cis configuration, an acetylenic chain of formula

 wherein R5 = H, 2-Cl, 3-Cl, 4-Cl, 3-NO2 or 3-CN, sequencing (methyl-4-pentyne-1) yl-1

 or (2-cyclohexylethyl-1-enyl) yl-1

 a phenethyl group of formula

 wherein R6 = H, C1, NO2 or CN, a benzoylmethyl group of formula

 in which R7 = Cl, NO2 or CN, a phenoxymethyl group of formula

 in which R7 has the same meanings as above, a benzyloxy group of formula

 in which R8 = 3-Br, 3-I, 3-SCF3, 3-CN Lenantiomer of absolute configuration.R (-) J, 3-CN [enantiomer of absolute configuration 3-CN (racemic form), 4-NR2, 4- NHCOCH 3, 4-NHSO 2 CH 3, 4-N (CH 3) -COCH 3 or 4-NH CH O, the (2-pyridazinyl) methyloxy linkage

 or (pyridinyl 3) methyloxy

 the sequence (butene-2) oxy (CH3-CH = CH3-CH-O-); (3-methyl-2-butene) oxy

 (cyclopentene-1-yl) methyloxy

 cyclobutylmethyloxy; (methyl1 cyclopentyl-1) methyloxy

 morpholino-2

 ; (tetrahydropyranyl-3) methyloxy-4-chlorobutoxy; (cyclohexanone 4-yl) methyloxy

 butoxy-4-one-2 (CH3 CO- (CH2) 2-O-); pentoxy-5-one-2 (CH3 CO- (CH2) 3-O-) or propoxy-3-one oxime 2

 a phenethyloxy sequence of formula

 in which R7 has the same meanings as before,. the metanitrodideuterobenzyloxy group  or

 methyl-4 (n) -pentyl group, - either a methylaminomethyl, N-isopropylaminomethyl group,  pyrrolidinomethyl or morpholinomethyl.  metanitrobenzyloxy group, either an aminomethyl or N, N-dimethylaminomethyl group, and  R then designates the metacyanobenzyloxy group, - an aminomethyl group, and R then designates the group  (3-chloro-5-nitro) benzyloxy, - either an acetyl group, and R then denotes the niethanol group.  trobenzyloxy, - is a 1-hydroxyethyl group, and R is then the  benzyloxy, metacyanobenzyloxy or metanitrobenzyloxy group,  the corresponding compounds of formula (I) being either under the  form of a mixture of four enantiomers, either under the form  of a couple of diastereoisomers erythro (E) and a couple  of diastereoisomers th = 'o (T), isolated pairs by separation  said mixture by high performance liquid chromatography,  erythro derivatives corresponding to the least  polar, - is a methoxy-1 ethyl group and R then designates a group  metanitrobenzyloxy, metacyanobenzyloxy or benzyloxy, the  corresponding compounds of formula (I) being either under the  form of a mixture of four enantiomers, either in the form  of a complex of diastereomers erythro (E) and a couple of  threo diastereoisomers (T), isolated liquid pairs by separation  of said mixture by chromatography / high performance, the  erythro derivatives being the least polar, - a dimethoxy-l, 1 methyl group and R then designates a  metacyanobenzyloxy, metanitrobenzyloxy, n-butoxy group,  cyclopentylmethyloxy or (2-cyano) ethoxy, - is a diethoxy-1, 1 methyl group and R then designates the  metachlorobenzyloxy group, or a dioxolane-1,3 yl-2 group and R then designates the  metanitrobenzyloxy group.  2. Process for the preparation of the compounds of formula (I) for which the set (X, A, R Rq) takes the value (S, O, H), R2 then representing the group -CH 2 COEt, or (O, O, H), R2 then representing the group -CH2-OCO-CH2-OC6H5, characterized in that it consists in condensing the compound of formula

 wherein X represents a sulfur or oxygen atom, with propionic acid or phenoxyacetic acid chloride.  3. Process for the preparation of the compounds of formula (I) for which the group (X, A, R 1) has the value (S, O, H) and R 2 represents the hydroxymethyl, methoxymethyl, ethoxymethyl or n-propyloxymethyl group, characterized in that it consists in cyclizing with thiophosgene the compounds of formula

 in which the pair (R ', Rg) takes any of the values

 4. Process for the preparation of the compound of formula (I) for which the group (X, A, R1, R2, R) takes the value (O, S, H, CH20CH3

 characterized in that it consists of cyelising by the formula pnosgene the compound of

 5.Process of preparing the compound of formula (I) for which the set (X, A, R1, R2, R) has the value (H2, CH2, H, CH20H,

 characterized in that it consists in reducing, preferably by the double hydride of lithium and aluminum, the compound of formula:

 6. Process for the preparation of the compounds of formula (1) for which the group (X, A, R1, R2) has the value (O, O, H, -CH2OCOC4R9t), characterized in that it consists in the reduction by the mercuric chloride-aluminum amalgam of the compound of formula

 and optionally treating the thus-obtained compound of formula

 by the formate of ethyl.  7. A process for the preparation of the compounds of formula (I) for which the group (X, A, R1, R2) takes the value (O, O, H, CH2 OCH3), R denoting then: a pheryl group of structure

 wherein R3 has the same meanings as in claim 1, a benzyl group, a trans-styryl group of structure

R'4 = H, C1, NO2 or CN, a cis-styryl group or metanitrostyryl (cis). a benzoylmethyl group of structural  where it,

 where R'7 = Q. characterized in that it consists in the cyclization with ethanolic potassium hydroxide or sodium methoxide of the compound of formula:

 wherein R "takes the particular values of R listed above.  8. Process for the preparation of the compounds of formula (I) defined in claim 7, characterized in that it consists in the cyclization preferably with sodium methoxide in toluene solution, of the compound of formula:

 in which R "has the same meanings as in formula (XI).  9. Process for the preparation of the compound of formula (I) for which the combination (x, A, R, R, R) has the meaning Cp, O, H, CH 2 OCH 3,

 characterized in that it consists in the reduction preferably by iron in the presence of ammonium chloride and in ethanolic medium, of the compound of formula (I) in which (X, A, R1, R2) = (O, O , H, CH20CE3) and R represents the trans metanitrostyryl group.  10. Process for the preparation of the compound of formula (I) for which the set (X, A, R1, R2, R) takes the value (O, O, H, CH2OCH3

 characterized in that it consists in the condensation of the compound of formula

 with the compound of formula:

 11. Process for the preparation of the compounds of formula (I) for which the combination (X, A, R, R) takes the value (O, O, H, CH 2 OCH 3) and R denotes either a phenylethynyl group of formula

  where R5 = H, 2-C1, 3-C1, 4-C1, 3-NO2 or 3-CN, ie the group (4-methyl-1-pentyl) or (cyclohexyl-2-ethyl-1-yl) l, characterized in that it consists in the condensation of copper acetylides of formulas

 where R5 has the same meanings as above, with the compound of formula:

 12. Process for the preparation of the compounds of formula (I) for which the group (X, A, R 1, R 2) has the value (O.O, H, CH 2 OCH 3) and R denotes a phenethyl group of formula

 in which R6 = H, C1, NO2 or CN, characterized in that it consists in the reduction preferably. by triethylsilane (SiEtRH) in the presence of trifluoroacetic acid, the compound of formula (I) for which the set (X, A, R1, R2) takes the value (O.O. H. CH 2 OCH 3) and R denotes the benzoylmethyl structural group

 wherein R6 has the same meaning as above.  13. Process for the preparation of the compounds of formula (I) for which the combination (X, A, R1, R2) takes the

 , CH2OCH3) and R denotes a phenoxymethyl group of structure in which R7 = C1, NO2 or CN, characterized in that it consists in the condensation of the compound of formula:

 with metachloro-, metacyano- or metanitrophenol.  14. Process for the preparation of the compounds of formula (I) for which the set (X, A, R1, R2) takes the value (o, O, H, CH 2 OCH 3) and R denotes a phenethyloxy group of structure

 Wherein R7 = C1, NO2 or CN, characterized in that it comprises the condensation of phenethylalcohol of formula

 in which R has the same meanings as above, with the compound 7 of formula

 15. Process for the preparation of the compounds of formula (I) for which the group (X, A, R 1, R 2) has the value (O, O, H, CH 2 OCH 3) and R denotes: a benzyloxy group of formula

 wherein R11 = 3-Br, 3-I, 4-NH2, 4-NHCoCH3  or 4-N (CH3) -COCH3,  the metanitro-dideuterobenzyloxy group,  the (pyridazinyl-2) methyloxy or (pyridinyl) group  3) methyloxy,  the sequence (butene-2) oxy, (methyl-3-butene-2)  oxy, (cyclopenten-1-yl-1) methyloxy, cyclobutyl  methyloxy, (1-methyl-1-cyclopentyl) methyloxy,  2-morpholino ethoxy, (tetrahydropyranyl-3) methyl  loxy, (cyclohexanone-1 yl-4) methyloxy or chloroA  butoxy, characterized in that it consists in the condensation of metabromobenzyl chloride or tosylate, metaiodobenzyl, (2-pyridazinyl) methyl, (3-pyridinyl) methyl, metanitrodideuterobenzyl, paraaminobenzyl, paraacetamidobenzyl or para N methyl acetamidobenzyl; or chlorinated, brominated, mesylated or tosylated derivative of the following alcohols: 2-butene-1-ol, 3-methyl-2-butene-1-ol, 1-hydroxymethyl-1-cyclopentene, 1-hydroxymethylcyclobutyl, 1-hydroxymethyl-1-methyl-cyclopentyl, 2-morpholino-ethanol 3-hydroxymethyltetrahydropyranyl and 4-hydroxymethylcyclohexanone; or else 1-bromo-4-chlorobutyl, with the compound of formula (XKVI).  16. Process for the preparation of the compounds of formula (I) for which the combination (X, A, Ra, R2) takes the value (O, O, H, CH 2 OCH 3) and R denotes a benzyloxy group of formula

 wherein R11 = 3-Br, 3-I, 4-NH2, 4-NHCoCH3  or 4-N (CH3) -COCH3,  . the metanitrodideuterobenzyloxy group,  . the (pyridazinyl-2) methyloxy or (pyridinyl) group  3) methyloxy,  . the sequence (butene-2) oxy, (3-methyl-2-butene)  oxy, (cyclopenten-1-yl-1) methyloxy, cyclobutyl  methyloxy, (methyl-1-eyclopentyl-1) methyloxy,  2-morpholino ethoxy, (tetrahydropyranyl-3) methyl  loxy, (cyclohexanone-1-yl-4) methyloxy or chloro-4  butoxy, characterized in that it consists in a so-called phase transfer reaction on the compound of formula

 wherein R '' 'is metabromobenzyloxy, metaiodobenzyloxy, (2-pyridazinyl) methyloxy, (3-pyridinyl) methyloxy, metanitrodideutero benzyloxy, paraaminobenzyloxy, (2-butene) oxy, (3-methyl-2-butene) oxy, ( cyclopent-1-yl-1) methyloxy, cyclobutylmethyloxy, (1-methyl-1-cyclopentyl) methyloxy, 2-morpholino-ethoxy, (3-tetrahydropyranyl) methyloxy, (1-cyclohexanonyl) methyloxy or 4-chloro-butoxy, at 1 using methyl sulfate and a phase transfer catalyst.  17. Process for the preparation of the compound of formula (I) for which the set (X, A, R1, R2, R) has the value (O, O, H, CH20CH3,

 characterized in that it consists in a so-called pnase transfer reaction, by methyl sulfate and a phase transfer catalyst, on the compound of formula

 18. Process for the preparation of the compound of formula (I) for which the set (X, A, R1, R2, R) has the value (O, O, H, CH20CH3,

 characterized in that it consists in the action of ethyl formate on the compound of formula (I) for which the set (X, A, R1 'R2, R) takes the value (o, O, H, CH20CH3,

 19. Process for the preparation of the compound of formula (I) for which the set (X, A, R1, R2, R) has the value (O, O, H, CH20CH3, CH3SO4NH

 characterized in that it consists in the action of mesyl chloride in a pyridine medium, on the compound of formula (I) for which the set (x, A, Ra, R2, R) takes the value (O, O , H, CH2OCH3, H2N

 20.Process for preparing the compound of formula

 (X, A, R 1, R 2, R) has the value (O, O, H, CH 2 OCH 3, characterized in that it consists in the action of copper trifluoromethylsulfide (CF 3 SCu) in HMPT medium, on the compound of formula (I) for which the set (X, A, R1, R2, R) takes the value (O, O, H, CH20CH3

 21. Process for the preparation of the compounds of formula (I) for which the group (X, A, R 1, R 2, R) takes the values (O, O, H, CH 2 OCH 3, CH 3 CO- (CH 2) 2 O) and (O, O, H, CH 2 OCH 3, CH 3 CO- (CH 2) 3-O), characterized in that it consists in the acid hydrolysis of the compound of formula

 wherein n is 2 or 3. 22. A process for preparing the compound of formula (I) wherein the set (X, A, R1, R2, R) is (O, O, H, CH20CH3,

 characterized in that it consists in the action of hydroxylamine hydrochloride, in the presence of pyridine and in ethanolic medium, on the compound of formula

 23. Process for preparing the compound of formula (I) of particular formula

 characterized in that it consists of a phase transfer reaction with methyl sulphate on the compound of formula:

 R configuration (-)  24.Procédé of preparation of the compound of formula (I) corresponding to the particular formula:

 characterized in that it consists in the eyelization by ethanolic potassium hydroxide of the compound of formula

 configuration (R).  25. Process for the preparation of the compounds of formula (I) for which the group (X, A, R1) has the value (O, O, H) and R2 represents the isopropylamino-methyl, morpholinomethyl, ethylaminomethyl, pyrrolidinomethyl and aminomethyl group or dimethylaminomethyl, characterized in that it consists in the condensation of compounds of formula:

  wherein R "" represents a metanitrobenzyloxy, metacyanobenzyloxy or metachloro-metanitrobenzyloxy group, with ammonia, ethylanine, isopropylamine, morpholine, pyrrolidine or dimethylamine.  26. Process for the preparation of the compounds of formula (I), erythro or threo, for which the group (X, A, R 1) has the value (O, O, H), R2 represents the 1-methoxyethyl chain and R denotes the metacyanobenzyloxy, metanitrobenzyloxy or benzyloxy group, characterized in that it consists in the treatment with methyl sulphate, according to a so-called phase-transfer reaction, of the compounds of formula (I), erythro or threo, for which l (X, A, R1) is (O, O, H), R2 is hydroxy-1 ethyl and R is metacyanobenzyloxy, metanitrobenzyloxy or benzyloxy.  27. Process for the preparation of the compounds of formula (I) used in the process according to claim 26, characterized in that it consists in the action of benzoyl, metacyanobenzyl chloride or tosylate or mesylate, or metanitrobenzyl mesylate on the compound of formula

 the condensation reaction being optionally followed by separation by high performance liquid chromatography (H.P.L.C.) giving the erythro and threo derivatives.  28. Process for the preparation of the compound of formula (I) for which the set (X, A, R1, R2) has the value (O, O, H, COCH3), characterized in that it consists of oxidation with dichloroacetic acid in the presence of dicyclohexanecarbodiimide (DCCI) in the mixture of threo and erythro derivatives of the compounds of formula (I) for which the combination (X, A, R 1, R 2, R) takes the value

 29.Procédé of preparation of the compounds of formula (I) for which the set (X, A, R1) takes the value (O, O, H) and the pair (R2, R) takes the value:

 characterized in that it consists in the action of methanol, ethanol, or ethylene glycol, in the presence of paratoluene sulphonic acid, on compounds of formula

 wherein R "'1' represents a metacyano-, metachloro- or metanitrobenzyloxy group, or the sequence n-butoy, cyclopropylmethyloxy, or 2-cyanoethoxy.  30. Process for the preparation of the compound of formula (I) for which the set (X, A, R 1, R 2, R) is (O, O, H, CH 2 OCH 3, methyl-4-n-pentyl) , characterized in that it consists in the action of methyl sulphate by a so-called phase-transfer reaction, on the compound of formula:

 31. As medicaments, in particular for the treatment of endogenous and exogenous depressive states, the compounds according to claim 1.  32. As synthesis intermediates necessary for the preparation of the compounds of formula (I), the compounds of formulas (XVIII), (XXIII), (XXVII), (Xc), Xf),