Patent EA-001518-B1 (EA)
Title: Intermediates for the preparation of 2-imidazoline-5-ones
Inventor: BUFORN ALBERT
IPC: C07D233/86
Filed: 1997-07-17
Abstract: 1. 2-thiothiazolidin-5-one compound of general formula (I):   in which: R1 is a (C1-C3) alkyl or phenyl radical, R2 is an aryl group chosen from phenyl or pyridyl, which is optionally substituted with 1 to 3 groups chosen from a halogen atom, a nitro or cyano group and a (C1-C3) alkyl radical, (C1-C3)-alkoxy radical; as well as salts thereof and the corresponding stereoisomers and in particular, when the radicals R1 and R2 are different, the optical isomers resulting from the presence of the asymmetric carbon atom bearing R1 and R2 radicals; with the exception of 4-ethyl-4-phenyl-2-thiothiazolidin-5-one. 2. Compound according to Claim 1, characterized in that: R1 represents a (C1-C3) alkyl radical, R2 represents a phenyl optionally substituted with a halogen atom, a cyano or nitro group or a methyl or methoxy radical. 3. Compound according to any of claims 1 or 2, characterized in that R2 is a phenyl and R1 is methyl. 4. Compound according to one of claims 1 to 3, characterized in that it is an enantiomer relative to the asymmetric carbon atom bearing R1 and R2. 5. Process for the preparation of the compound of formula (I) as defined in one of Claims 1 to 4, characterized in that a compound of formula (II) is reacted with carbon bisulfide, in a solvent or a mixture of solvents, at a temperature of between 0 degree C and +50 degree C, according to the scheme:   in which R3 is an amino or hydroxyl group or a linear or branched alkoxy radical containing from 1 to 6, preferably from 1 to 3, carbon atoms or a benzyloxy radical optionally substituted with a halogen atom. 6. Preparation process according to claim 5, characterized in that it is carried out at a temperature of between 20 and 40 degree C if necessary in the presence of base. 7. Process for the preparation of the compound of formula (VI):   R1 is a (C1-C3) alkyl or phenyl radical, R2 is an aryl group chosen from phenyl or pyridyl, which is optionally substituted with 1 to 3 groups chosen from a halogen atom, a nitro or cyano group and a (C1-C3)-alkyl radical, (C1-C3)-alkoxy radical; R4 represents a hydrogen atom or an acyl radical; R5 represents an aryl or heteroaryl radical chosen from: phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, thienyl, benzothienyl, furyl, benzofuryl, quinolinyl, isoquinolinyl or methylenedioxyphenyl, each of these radicals optionally being substituted with 1 to 7 groups, which may be identical or different, preferably from 1 to 3, chosen from the meanings of R51 radicals, which represents: - a halogen atom or - an alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio-, haloalkylthio- or alkylsulphonyl radical, which is linear or branched, with 1 to 6 carbon atoms, or - a cycloalkyl, halocycloalkyl, alkenyloxy-, alkynyloxy-, alkenylthio- or alkynylthio-radical of 3 to 6 carbon atoms, or - a nitro or cyano group, or - an amino radical unsubstituted or mono- or disubstituted with an alkyl or acyl radical of 1 to 6 carbon atoms or alkoxycarbonyl radical of 2 to 6 carbon atoms, salts thereof and the corresponding stereoisomers, characterised in that the compound of formula (I); as defined in one of claims 1 to 4, is reacted with a compound of formula (V) in a solvent, and at a temperature of between +20 degree C and +100 degree C, preferably, between 40 and 80 degree C, according to the scheme:   8. The process according to claim 7, characterized in that it is carried out in the presence of a catalyst chosen from a tertiary amine such as triethylamine or tributylamine (or an organic salt of this amine, such as tributylamineacetate), the said catalyst being present in a catalyst/compound (I) proportion ranging from 0.05 to 1, preferably from 0.1 to 0.5.