Patent IE-41900-B1 (IE)
Title: (54)furo(3,4-b)furan derivatives, and their use in pharmaceutical compositions
IPC: C07D493/02
Filed: 1975-09-09
Abstract: 1489412 Furofurans IMPERIAL CHEMICAL INDUSTRIES Ltd 4 Sept 1975 [27 Sept 1974] 42040/74 Heading C2C [Also in Division A5] The invention comprises compounds of the formula where R1 is a hydrogen tom, an alkyl radical of from 1 to 10 carbon atoms or a phenyl radical; R2 is a hydrogen atom or a phenyl radical; and wherein R3 is a hydrogen atom or an alkyl radical of from 1 to 10 carbon atoms and R4 is a hydrogen atom or an alkoxycarbonyl radical of from 2 to 10 carbon atoms; or, when R2 is a hydrogen atom, R3 is a hydrogen atom and R4 is a radical of the formula R5SCH 2 -, wherein R5 is a benzyl radical or a phenyl radical optionally bearing one or two substituents selected from halogen atoms, alkyl and alkoxy radicals each of from 1 to 4 carbon atoms, and carboxylic acid radicals; or R3 and R4 together form the methylene radical (= CH 2 ); but excluding such compounds wherein: (a) R1 is an n-butyl radical, R2 is a hydrogen atom, and either R3 is a hydrogen atom and R4 is a hydrogen atom or a methoxycarbonyl radical, or R3 is a methyl radical and R4 is a hydrogen atom, or R3 and R4 together form the methylene radical; (b) R1 is an ethyl isopropyl or npentyl radical and R2, R3 and R4 are all hydrogen atoms; (c) R1 is a methyl radical, R2 is a phenyl radical, R3 is a hydrogen atom or a methyl radical, and R4 is a hydrogen atom; or (d) R1 is a hydrogen atom or a phenyl radical, R2 is a phenyl radical; and R3 and R4 are hydrogen atoms. The compounds may be prepared by a method which comprises (a) for a compound of Formula I wherein R4 is an alkoxycarbonyl radical of from 2 to 10 carbon atoms, oxidizing the olefinic bond in a compound of the formula where R6, R7 and R8 are each alkyl of 1 to 9 carbon atoms and cyclizing the product thereby obtained by reaction with an acid; (b) for a compound of Formula I wherein R4 is hydrogen, the stages of (i) hydrolysing the corresponding compound of Formula I wherein R4 is an alkoxycarbonyl radical of from 2 to 10 carbon atoms and then (ii) decarboxylating the intermediate compound of Formula I obtained wherein R4 is a carboxylic acid radical; (c) for a compound of Formula I wherein R3 and R4 together form the methylene radical, reacting a carboxylic acid of the formula with formaldehyde; (d) for a compound of Formula I wherein R3 is a methyl radical and R4 is a hydrogen atom, reducing the corresponding compound of Formula I wherein R3 and R4 together form the methylene radical; (e) for a compound of Formula I wherein R2 and R3 are hydrogen atoms and R4 is a radical of the formula R5SCH 2 -, reacting the corresponding compound of Formula I wherein R3 and R4 together form the methylene radical, with a thiol of the formula R5-SH; (f) for a compound of Formula I wherein R2, R3 and R4 are each hydrogen atoms, cyclising a compound of the formula wherein R7 is an alkyl radical of from 1 to 9 carbon atoms; (g) for a compound of Formula I wherein R3 is an alkyl radical of from 1 to 10 carbon atoms and R4 is an alkoxycarbonyl radical of from 2 to 10 carbon atoms, alkylating the corresponding compound of Formula I wherein R3 is a hydrogen atom and R4 is an alkoxycarbonyl radical of from 2 to 10 carbon atoms by reaction with an alkyl halide of the formula R9X, wherein R9 is an alkyl radical of from 1 to 10 carbon atoms, and X is a displaceable radical; (h) for a compound of Formula I wherein R2 is a phenyl radical, R3 is a hydrogen atom or an alkyl radical of 1 to 10 carbon atoms and R4 is a hydrogen atom or an alkoxycarbonyl radical of from 2 to 10 carbon atoms, reacting a succinic anhydride derivative of the formula with a compound of the formula The invention further comprises racemic compounds of Formula I wherein R1 is an n-butyl radical, R2 and R4 are hydrogen and R3 is a methyl radical. These compounds are prepared by hydrolysing and decarboxylating the corresponding racemic compound of the formula or by reducing racemic canadensolide or 6-epicanadensolide in the presence of a palladium catalyst.