PROCEDIMIENTO PARA PREPARACION DE DERIVADOS SUSTITUIDOS DE GEM-DIARIAL-ETILENO.

摘要

1320481 Gem-diaryl ethylene derivatives PFIZER Ltd 11 Jan 1972 [11 Jan 1971] 1252/71 Heading C2C Novel compounds of general Formula I and their acid addition salts in which R is a phenyl or 2-thienyl group, R 1 is a p-R2-phenyl or 5-R2-thien-2-yl group where R2 is an alkyl, cycloalkyl or cycloalkyl-alkyl group each of which contains 3 to 6 C atoms and Y is either (1) a group =CR5-alk-NR3R4 in which R5 is hydrogen, methyl or ethyl, alk is a group chosen from methylene, ethylidene, propylidine, ethylene, 1 or 2 methylethylene or tri-methylene with the proviso that = CR5- alkcontains no more than 4 C atoms and R3 and R4 each represent a C 1-4 alkyl group or together with the N atom to which they are attached form a saturated heterocyclic group or (2) an amino-cyclic group of formula = CR5-C n H 2n -CHZ or =CZ in which n is 0 to 2, R5 is hydrogen, methyl or ethyl with the proviso that =CR5-C n H 2n contains not more than 3 C atoms and Z is a divalent group which completes a saturated heterocyclic ring containing at least one nitrogen atom and at least 4 C atoms, the number of C atoms in the shortest chain of C atoms separating any N atom from the C atom to which the amino-cyclic group is attached being 3 or 4, are prepared by (1) reacting a compound of Formula II or III in which R6 is hydrogen, methyl or ethyl and R5 and R6 do not contain more than 2 C atoms with the corresponding lithium derivatives of R 1 H or RH followed by dehydration of the resulting carbinol, (2) the Wittig reaction of a ketone RR 1 C = O with an aminoalkyltriphenyl phosphonium bromide of general formula in which alk represents a divalent saturated aliphatic hydrocarbon group containing 2 to 3 C atoms, in the presence of a strong base or (3) reaction of a ketone RR 1 C = O with a Grignard reagent of formula Mg-Hal-A in which A is (i) HCR5-alk-NR3R4 in which -alkis a divalent saturated aliphatic hydrocarbon group containing 2 or 3 C atoms, the free valences being located on different C atoms, and dehydrating the resulting carbinol. The compounds of Formula I in which Y is asymmetric form cis and trans isomers (with respect to R) which may be isolated by fractional crystallization. The cis isomer may be converted to the trans by U.V. irradiation. Compounds of Formula (I) and in particular the trans isomer exhibit anti-histamine action at " H 2 " receptor sites and form with a carrier a pharmaceutical composition which may be administered orally or parenterally.