GB1098347A - New oxepin derivatives, their production and use - Google Patents

Abstract

The invention comprises dibenzoxepins of the formula <FORM:1098347/C2/1> wherein X1, X2, Y1 and Y2 represent hydrogen, chlorine or bromine atoms, or C1- 4 alkyl or C1- 4 alkoxy radicals, R1 represents a hydrogen atom or a methyl radical and R2 and R3 each represents a hydrogen atom or a C1- 4 alkyl radical, or R2 and R3 together with the adjacent nitrogen atom and, optionally, with the inclusion of an oxygen atom or an imino, C1- 6 alkylimino or C1- 6 hydroxyalkylimino group as ring member, represent a saturated heterocyclic radical having 5 to 7 ring members; acid-addition salts thereof; and a process for their preparation comprising reacting a reactive ester of a hydroxyl compound of the formula <FORM:1098347/C2/2> with an amine of the formula <FORM:1098347/C2/3> or with a metal compound of an N-acyl derivative of a C1- 4 alkylamine, if necessary hydrolysing the reaction product to split off any acyl radical bound to the nitrogen atom of the side chain, if desired treating a compound of Formula I having an imino group as ring member with an alkylene oxide having at most 6 carbon atoms or with a reactive monoester of an alkane diol having at most 6 carbon atoms and, if desired, converting a compound of Formula I into a salt with an organic or inorganic acid. 2 - Methoxy - 11 - bromomethyl - dibenz[b,f]-oxepin is prepared by esterifying 2-phenoxy-5-methoxybenzoic acid with ethanol to form 2 - phenoxy - 5 - methoxybenzoic acid ethyl ester, reducing this compound with LiAlH4 to form, 2-phenoxy-5-methoxybenzyl alcohol, reacting this compound with phosphorus tribromide to form 2 - phenoxy - 5 - methoxybenzyl bromide, reacting this compound with potassium cyanide to form 2 - phenoxy - 5 - methoxyphenyl acetonitrile, hydrolysing this compound with aqueous KOH to form 2-phenoxy-5-methoxyphenyl acetic acid, cyclising this compound by treatment with polyphosphoric acid to form 2-methoxy-dibenz [b,f]-oxepin, reacting this compound with methyl iodide to form 2-methoxy-11-methyldibenz[b,f] - oxepin - 10(11H) - one, reducing this compound with LiAlH4 to form 2-methoxy-11 - methyl - 10,11 - dihydro - dibenz[b,f]-oxepin-10-ol, reacting this compound with thionyl chloride to form 2 - methoxy - 10 - chloro - 11 - methyl - 10,11 - dihydro - dibenz[b,f] - oxepin, dehydrochlorinating this compound by treatment with potassium tertiary butylate to form 2 - methoxy - 11 - methyl - dibenz[b,f] - oxepin, and finally brominating this compound by treatment with N-bromosuccinimide. 10 - Bromomethyl-, 10 - (a - bromoethyl)- and 2 - chloro - 11 - bromomethyl - dibenz[b,f] - oxepins are prepared by brominating 10-methyl-, 10-ethyl and 2 - chloro - 11 - methyl - dibenz[b,f]-oxepins with N-bromosuccinimide. Pharmaceutical compositions having adrenolytic and central depressant activity, for oral, rectal or parenteral administration comprise a compound of the invention together with a pharmaceutical carrier.