Patent EA-000831-B1 (EA)
Title: Novel substituted [2-(1-piperazinyle)etoxy]methyl compounds, method for preparing said compounds and the use thereof
Inventor: DUCHENE GUY
IPC: C07D295/088
Filed: 1997-03-28
Abstract: 1. Novel substituted [2-(1-piperazinyl)ethoxy]methyl compounds of formula (I)   wherein R1 is -CONH2, -CN, -COOH, -COOM or -COOR3, where M is an alkali metal and R3 is C1-C4 alkyl; and R2 is a hydrogen atom ome or a -COR4 or -R5 group, where R4 is selected from -OR6 or -R7 groups, wherein  R5 is allyl or alkylaryl, R6 is a straight or branched C1-C4 alkyl, halogenoalkyl, alkylaryl, alkylnitroaryl or alkylhalogenoaryl, and R7 is halogenoalkyl 2. A substituted [2-(1-piperazinyl)ethoxy]methyl compound of claim 1, wherein selected from  2-(l-piperazinyl)ethoxyacetic acid, 2-[2-(l-piperazinyl)ethoxy]acetamide, 2-(l-piperazinyl)ethoxyacetonitrile, 2-(1-piperazinyl)ethoxyacetatemethyl, 2-(l-piperazinyl)ethoxyacetateethyl, 2-(4-benzyl-1-piperazinyl)ethoxyacetamide, 2-(4-benzyl-1-piperazinyl)ethoxyacetonitrile, 2-(4-benzyl-l-piperazinyl)ethoxyacetatemethyl, 4-(2-carbamoylmethoxyethyl)-piperazine-1-carboxylatebenzyl, 4-(2-cyanomthoxyethyl)-piperazine-l-carboxylatebenzyl, 4-(2-carbamoylmethoxyethyl)-piperazine-l-carboxylatetertbutyl, 4-(2-cyanomethoxyethyl)-piperazine-1-carboxylatetertbutyl, 4-(2-methoxycarbonylmethoxyethyl)-piperazine-l-carboxylatetertbutyl, 4-(2-carbamoylmethoxyethyl)-piperazine-1-carboxylateethyl, 2-(4-carboxyethyl-1-piperazinyl)ethoxyacetatepotassium. 3. A substituted [2-(1-piperazinyl)ethoxy]methyl compound of claim 1, wherein the group protecting R2 amine function is a straight or branched alkylcarboxylate group, containing 1 to 4 carbon atoms, or a alkylaryl group. 4. A method for preparing [2-(l-piperazinyl)ethoxy]methyl of claims 1-3, wherein the piperazine of formula   wherein R2 is a hydrogen atom or -COR4 or R5, wherein R4 is selected from -OR6 or -R7 groups, in which R5 is allyl or alkylaryl radical, R6 is a straight or branched alkyl radical, containing 1 to 4 carbon atoms, halogenoalkyl, alkylaryl, alkylnitroaryl or alkylhalogenoaryl, R7 is halogenoalkyl reacts with a substituted [2-haloetoxy]methyl compound of formula X-CH2-CH2-O-CH2-R1 wherein R1 is -CONH2, -CN, -COOH, -COOM or -COOR3 group, M is an alkali metal, R3 is C1-C4 alkyl and X is a halogen atom. 5. A method of claim 4, wherein a halogen atom designated as X is chlorine or iodine. 6. A method of claim 4 or 5, wherein the protection group for R2 amine function is a straight or branched alkyl carboxylate group, containing 1 to 4 carbon atoms, or alkylaryl group. 7. Use of a substituted [2-(1-piperazinyl)ethoxy]methyl compounds of formula   wherein R1 is -CONH2, -CN, -COOH, -COOM or -COOR3 group, M is an alkali metal, R3 is C1-C4 alkyl and R2 is a hydrogen atom as an intermediate product for preparing compounds of formula   wherein R1 has the above value in formula (I) and X1 and X2 are independently hydrogen, fluoro, chlorine and/or bromine. 8. A method for preparing compounds of formula   R1 is -CONH2, -CN, -COOH, -COOM or -COOR3 group, M is an alkali metal, R3 is C1-C4 alkyl and X1 and X2 are independently hydrogen, fluoro, chlorine and/or bromine, wherein a substituted [2-(1-piperazinyl)ethoxy]methyl compound of formula   wherein  R1 is -CONH2, -CN, -COOH, -COOM or -COOR3 group, M is an alcali metal, R3 is C1-C4 alkyl and R2 is a hydrogen atom, reacts with diphenylmethanehalogenide of formula   wherein X is halogen, selected from chlorine, bromine or iodine and X1 and X2 are independently hydrogen, fluoro, chlorine and/or bromine. 9. A method of claim 8, wherein a substituted [2-(l-piperazinyl)ethoxy]methyl of formula (I), wherein R2 is a hydrogen atom and is a product of the cleavage reaction of the R2 group a substituted [2-(l-piperazinyl)ethoxy]methyl of formula (I), wherein R2 is a hydrogen atom or -COR4 or R5 group, where R4 is selected from OR6 or R7 groups, wherein  R5 is allyl or alkylaryl radical, R6 is a straight or branched alkyl radical, containing 1 to 4 carbon atoms, halogenoalkyl, alkylaryl, alkylnitroaryl or alkylhalogenoaryl, R7 is halogenoalkyl. 10. Use of the compounds of formula   wherein  R1 is -CONH2, -CN, -COOH, -COOM or -COOR3 group, M is an alkali metal, R3 is C1-C4 alkyl and X1 is a chlorine atom in position 4 and X2 is a hydrogen atom obtained by a method of claim 8 as intermediate compounds for preparing 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxylacetic acid and/or pharmaceutically acceptable salts thereof. 11. Use of the compounds of formula   wherein  R1 is -CONH2, -CN, -COOH, -COOM or -COOR3 group, M is an alkali metal, R3 is C1-C4 alkyl and X1 and X2 each is a fluoro atom in position 4, obtained by a method of claim 8 as intermediate compounds for preparing 2-[2-[4-[bis(4-fluorophenyl)phenylmethyl]-1-piperazinyl]ethoxyacetic acid and/or pharmaceutically acceptable salts thereof.