Process for the preparation of pharmaceutically Active fenipolieno carboxylic derivatives

摘要

1514975 Preparation of polyene compounds; phosphonium compounds F HOFFMANN-LA ROCHE & CO AG 26 Sept 1975 [26 Sept 1974] 39545/75 Heading C2C Polyene compounds of the general formula wherein one of the symbols R 1 and R 2 represents a halogen atom or a lower alkyl group and the other symbol represents a halogen atom or a lower alkoxy group, the symbols R 3 and R 5 each represent a hydrogen or halogen atom or a lower alkyl group with the proviso that one of the symbols R 3 and R 5 represents other than a halogen atom, the symbol R 4 represents a halogen atom or a lower alkoxy, amino, mono- (lower alkyl)amino or di-(lower alkyl)amino group and the symbol R 6 represents a formyl, hydroxymethyl, alkoxymethyl, alkanoyloxymethyl, carboxyl, alkoxycarbonyl, alkenoxycarbonyl. alkynoxycarbonyl, carbamoyl, mono- (lower alkyl)carbamoyl, di - (lower alkyl)carbamoyl or N-hetero-cyclylcarbonyl group, and salts thereof, are prepared by reacting a compound of the general formula with a compound of the general formula wherein the symbol m stands for zero and the symbol n stands for 1 or the symbol m stands for 1 and the symbol n stands for zero, one of the symbols A and B represents the formyl group and the other symbol represents either a triarylphosphiniummethyl group of the formula in which the symbol X represents an aryl group and the symbol Y represents the anion of the organic or inorganic acid, or a dialkoxyphosphinylmethyl group of the formula in which the symbol Z represents an alkoxy group; or one of the symbols A and B represents a halomethyl, alkylsulphonyloxymethyl or arylsulphonyloxymethyl group and the other symbol represents a sulphonylmethyl group of the formula in which the symbol E represents an aryl or aralkenyl group which may carry one or more electron-repelling to electron-weakly attracting substituents; the symbol R 7 represents a carboxyl, alkoxycarbonyl, alkenoxycarbonyl, alkynoxycarbonyl, di - (lower alkyl)carbamoyl or N-heterocyclylcarbonyl group; or the symbol R 2 also represents an alkoxymethyl or alkanoyloxymethyl group when the symbol B represents the formyl group; or the symbol R 7 also represents a formyl, alkoxymethyl or alkanoyloxymethyl group when the symbol B represents a halomethyl, alkylsulphonyloxymethyl or arylsulphonyloxymethyl group; or the symbol R 7 also represents a formyl group when the symbol B represents a triarylphosphoniummethyl group, a dialkoxyphosphinylmethyl group or a sulphonylmethyl group, and cleaving off a sulphone group which may be present in the reaction product to form an additional carbon-carbon bond, and, if desired, converting an acid obtained or an amine obtained into a salt, or converting a carboxylic acid of Formula I into a carboxylic acid ester of Formula I or into an amide of Formula I, or converting a carboxylic acid ester of Formula I into a carboxylic acid of Formula I or into an amide of Formula I, or reducing a carboxylic acid of Formula I into a carboxylie acid ester of Formula I to the corresponding alcohol of Formula I and if desired etherifying or esterifying said alcohol, or saponifying an alcohol ester of Formula I, or oxidizing an alcohol or alcohol ester of Formula I to the corresponding carboxylic acid. The compounds have pharmaceutical properties. Phosphonium compound starting materials of the skeletal structure of Formula II in which A represents a triaryl phosphonium group -CH 2 -P[X]SP+/SP 3 Y- in which X refers to an aryl group and Y is Cl are prepared in Examples 1 to 6. Other intermediates are 2 - chloro - 3,5,6 - trimethyl - benzene, 2- chloro - 4 - nitro - 3,5,6 - methyl benzene, 4 - amino - 2 - chloro - 3,5,6 - trimethyl benzene, 2 - chloro - 4 - hydroxy - 3,5,6 - trimethyl benzene, 2 - chloro - 4 - methoxy - 3,5,6- trimethyl benzene - 4,4SP1 /SP- dimethoxy - 3- methyl - but - 1 - yne - 3 - ol 2 formyl - 4- chloro - but - 2 - ene and 7 - formyl - 3 - methylocta - 2,4,6 - triene - 1 - oio acid ethyl ester.