Patent GB-1390082-A (GB)
Title: Dibenzocycloheptene derivatives
IPC: C07C62/38
Filed: 1972-04-07
Abstract: 1390082 Methanodibenzocyloheptene derivatives F HOFFMANN-LA ROCHE & CO AG 7 April 1972 [8 April 1971] 16173/72 Heading C2C Compounds of the Formula (I) wherein A represents a direct bond or an alkylene or alkenylene group containing up to 3 carbon atoms, R 1  and R 2  each represent a hydrogen atom or an alkyl group or R 1  and R 2  together with the nitrogen atom to which they are attached represent a heterocyclic ring which may contain an oxygen atom or a further nitrogen atom optionally substituted by an alkyl or hydroxyalkyl group, R 3  represents a hydrogen atom or an alkyl group and R 4  represents a hydrogen atom or an alkoxy group, or, when A represents an alkylene or alkenylene group, R 4  may also represent a hydroxy group, or R 3  and R 4  together represent an oxo group, R 5  and R 6  each represent a hydrogen or halogen atom and R7 represents a hydrogen atom or a hydroxy group, are obtained by (a) reacting a compound of Formula (II) wherein A 1  is alkylene or alkenylene of up to 3C, X is a leaving atom or group, R<SP>1</SP> 3  is H or alkyl, R<SP>1</SP> 4  is H or alkoxy, with an amine of formula R 1 R 2 NH, or (b) reducing an acid amide of Formula (IV) where A 2  is a direct bond or a C 1-2  alkylene or alkenylene group, R 3  is H or alkyl, R 8  is H, alkoxy, hydroxy or acyloxy, or R 3  and R 8  together represent an oxo group, with a complex metal hydride to form the corresponding amino compound, or (c) reducing a carbamic ester of the Formula (V) where R 3  is H or alkyl, R 9  is H or alkoxy, or when A is alkylene or alkenylene, R 9 ) can also be hydroxy or acyloxy, or R 3  and R 9  together denote oxo, R 10  is alkyl, with a complex metal hydride to the corresponding methylamino compound, or (d) decarboxylating a carbamic acid corresponding to Formula I in which R 1  is H and R 2  is COOH, or (e) treating a compound of Formula VII wherein B is A 3 -R 12  or A,-NO 2 , R 11  is H, alkoxy or hydroxy, R<SP>1</SP> 3  is H or alkyl, R 12  is one of the groups -CH=N-R 13 , -CH=N-OH and -CN, R 13  is alkyl, A 3  is C 1-2  alkylene or alkenylene, A 4  is alkenylene of up to 3C, with a reducing agent, or (f) reductivity aminating a compound of the Formula (VIII) wherein R 14  is H or alkyl, (A 2  and R 14  together containing at most 2C atoms) with an amine R 1 R 2 NH, or (g) reducing a compound of Formula I in which R 3  and R 4  together denote oxo to the corresponding methylene compound, or (h) oxidizing a hydroxy compound of Formula I in which R 3  is H and R 4  is OH, to the corresponding oxo compound, or (i) reducing an oxo compound of Formula I, in which R 3  and R 4  together represent oxo, and R 1  and R 2  each represent H or alkyl, to the corresponding hydroxy compound, or (j) subjecting an ether of the Formula I in which R 3  is H or alkyl and R 4  is -O alkyl to an ether cleavage, or (k) reductively eliminating a leaving group denoted by X in a compound of Formula I in which R 3  is H or alkyl and R 4  is a leaving group X, or (e) hydrogenolytically cleaving off the thioketal group in a compound of Formula I in which R 3  and R 4  together denote an open or cyclic thioketal group, in the presence of Raney nickel, or (m) cleaving off the protecting group in a compound of Formula I in which R 3  is H or alkyl, R 4  is H or alkoxy, or when A is alkylene or alkenylene, R 4  can also be hydroxy or acyloxy, or R 3  and R 4  together denote oxo, R 2  is H or alkyl, and R 1  is a protecting group, or R 1  and R 2  together denote a protecting group, or (n) reductively cleaving off the hydroxy group in a compound of Formula I in which R 3  is H or alkyl and R 4  is OH, or (o) alkylating a compound of Formula I in which R 1  is H, or (p) demethylating a compound of Formula I in which R 1  and R 2  are each CH 3 , and (q) if desired, separating the geometrical and/or optical isomers from an isomer mixture obtained, and (r) if desired, converting the product into a salt. Intermediates of Formula II are obtained by reducing a corresponding compound in which X is -COOH into the alcohol, and the hydroxyl group is converted in known manner into a leaving group. The carboxylic acids can also be converted to amides and nitriles for use as intermediates. Many other intermediates are also described. A pharmaceutical preparation having antidepressant, antineuroleptic and anticonvulsant properties comprises a compound of Formula I in association with a compatible pharmaceutical carrier, preferably in forms suitable for enteral or parenteral administration. Reference has been directed by the Comptroller to Specifccation 1,277,870.