Patent GB-1040738-A (GB)
Title: Azepine derivatives and process for their production
IPC: C07D401/06
Filed: 1964-12-15
Abstract: The invention comprises compounds of the formula <FORM:1040738/C2/1> wherein X represents the ethylene or vinylene group, R1 represents a C1- 4 alkyl group, R2, R3 and R4 represent hydrogen atoms or C1- 4 alkyl groups, R5 represents a C1- 4 alkyl or aralkyl group or, together with R3, an alkylene radical having 2 to 4 chain members or, with R4, an alkylene radical having 4 to 6 chain members which may be optionally interrupted by an oxygen or sulphur atom, the imino group, or an alkylimino hydroxyalkylimino or alkanoyl oxyalkylimino group, each alkyl group having at most 4 carbon atoms, m and n represent 0, 1 or 2 and together they are 1, 2 or 3; and acid addition salts thereof. The compounds are prepared by (a) reacting, in the presence of a condensing agent, a compound of the formula <FORM:1040738/C2/2> wherein R21 has the meaning of R2 above or is a C1- 4 alkanoyl radical, with a reactive ester of an amino alcohol of the formula <FORM:1040738/C2/3> wherein R41 has the meaning of R4 above, or is an arylmethyl radical and, if necessary, hydrogenolysing or hydrolysing the resulting compound, or (b) reacting a reactive ester of a hydroxyl compound of the formula <FORM:1040738/C2/4> with an amine of the formula <FORM:1040738/C2/5> or (c) reducing, by means of a complex metal hydride, in an organic solvent, the carbonyl group to the methylene group or reducing the alkoxycarbonyl group to the methylene group in a compound of the formula <FORM:1040738/C2/6> wherein R41, R51, (CH2)m1 and (CH2)n1 have the meanings given above for R4, R5, (CH2)m, and (CH2)n but in at least one of these groups R41, R51, (CH2)m1 and (CH2)n1 a methylene group bound to the nitrogen is replaced by a carbonyl group, or R51 is an alkoxycarbonyl group, the alkyl group having up to 4 carbon atoms and R41, (CH2)n1 and (CH2)m1 have the meanings given above for R4, (CH2)n and (CH2)m, or (d) reducing, by means of a complex metal hydride, in an organic solvent, the carbonyl group to the methylene group in a compound of the formula <FORM:1040738/C2/7> wherein R511 is a hydrogen atom or an alkyl radical containing one methylene group less than R5, or (e) hydrolysing a compound of the formula <FORM:1040738/C2/8> wherein R6 represents an organic radical or R5 and R6 together represent an alkylene radical having 4 or 5 chain members which is interrupted by an imino group substituted by an organic acid radical, or (f) hydrogenolysing a compound of the formula <FORM:1040738/C2/9> wherein R7 represents a C1- 4 alkyl or benzyl radical, and R8 represents an aralkyl radical containing at least one aryl group in the a -position or, if R7 is the benzyl group, R8 is also a C1- 4 alkyl radical, or R5 and R8 together form an alkylene chain having 4 or 5 chain members.  3 - Alkylamino- or 3 - dialkylamino - 5 - halogenalkyl - 5H - dibenz[b,f]azepines and their 10,11-dihydro derivatives are prepared by condensing alkali metal compounds of 3-alkylamino-or 3-dialkylamino-5H-dibenz[b,f]azepines and their 10,11-dihydro derivatives with non-geminal dihalogen alkanes.  Compounds of the Formula VIII are prepared by reacting compounds of the Formula I in which R2 and R4 represent C1- 4 alkyl groups with one mol. equivalent of an organic acid or halide or anhydride thereof, e.g. ethyl formate or ethyl chloro formate.  Pharmaceutical compositions which potentiate the action of noradrenaline and antagonise that of reserpine, tetrabenazine, serotonin and chlorpromazine and have myotropic spasmolytic properties, for oral or parentel administration, comprise a compound of the invention together with a pharmaceutically acceptable carrier.