Patent GB-1148740-A (GB)
Title: 5,10-epoxy-5-(aminopropyl)-dibenzocycloheptenes
IPC: C07D493/08
Filed: 1966-08-18
Abstract: 1,148,740. 5,10 - Epoxy - dibenzocycloheptenes. MERCK & CO. Inc. 18 Aug., 1966 [23 Aug., 1965], No. 37077/66. Addition to 1,074,081. Heading C2C. The invention comprises (1) novel compounds of the Formulµ (I), (II), (III), (IV) and (V) (wherein NR<SP>1</SP>R<SP>11</SP> is C 1-6  alkylamino, except in the amine oxides, di-(C 1-6  alkyl)-amino, or saturated heterocyclic amino of 5 or 6 ring atoms containing NH, N(C 1-4  alkyl), or O as the optional additional hetero atom or atoms; A is C 1-5  alkyl and Z is acyloxy of the formula R*.COO-, Q.COO- or C 6 H 5 (CH 2 ) n COO- where the benzene ring may be substituted by one, two or three halogen, CF 3 , C 1-5  alkyl or C 1-5  alkoxy substituents, R<SP>*</SP> is alkyl, Q is an unsaturated aliphatic hydrocarbon radical and n is zero, 1, 2 or 3; or A is H and Z is C 1-5  alkylsulphonylamino, C 6 H 5 (CH 2 ) n SO 2 NH- wherein the benzene ring may be substituted as defined above, or Q.COO- or C 6 H 5 (CH 2 ) n COO- as defined above; or, when NR<SP>1</SP>R<SP>11</SP> is monoalkylamino, A is H and Z is C 2-6  alkanoyloxy; or Z and A together are R*.COON=, Q.COON = or CH 6 (CH 2 ) n COON= as defined for similar radicals above, hydrazono or C 1-5  alkoxyimino; X and X<SP>1</SP> are H, halogen, C 1-6  alkyl, C 2-6  alkenyl, CF 3 , OH, C 1-4  alkoxy, SH, C 1-4  alkylthio, C 1-4  alkylsulphonyl or SONH 2  which may be mono- or di-(C 1-4  alkyl) substituted, more than one substituent being optionally present on each benzene ring; R<SP>111</SP> is C 1-6  alkyl; R is H, OH, oxo, hydroxyimino or NH 2  which may be mono-(C 1-6  alkyl) substituted, or R is OH and C 1-6  alkyl on the same carbon atom; R<SP>1</SP> in NR<SP>1</SP>.COOR<SP>6</SP> is C 1-6  alkyl; R<SP>6</SP> is alkyl, aralkyl or aryl; and Z<SP>0</SP> is OH, C 1-5  alkoxyimino, C 1-6  alkylamino, C 1-5  alkylsulphonylamino or C 6 H 5 - (CH 2 ) n SO 2 NH- (as above defined) and their acid-addition salts, and, where appropriate, N-oxides; (2) the novel 5-[3-(N-carbethoxy-N- methylamino) - propyl] - 10,11 - dihydro - 5,10- epoxy - 11 - hydroxy - 11 - methyl - 5H - dibenzo-[a,d]-cycloheptene; (3) certain novel epoxy-dibenzocycloheptenes falling within Claims 1 and 6 of Specification 1,074,081; (4) the preparation of compounds of the Formula (VI) by dealkylation of the corresponding dialkylamino compounds by reaction with a haloformate ester followed by hydrolysis; (5) the preparation of the 11-alkoxyimino compounds of Formula (I) by treatment of the corresponding 11-ketones with the appropriate alkoxyamine in an inert solvent, the starting materials being prepared by Oppenauer oxidation of the 11-ols; (6) the reduction of the 11- alkoxyimino products of (5) to the corresponding 11-amino compounds; (7) the preparation of the 11-acyloxy compounds of Formula (I) by acylation of the corresponding 11-ols; (8) the preparation of the 11-acyloxyimino compounds of the Formula (I) by acylation of the corresponding 11-hydroxyimino compounds, monoalkylamino starting materials in this and method (7) being used as their acid-addition salts; (9) the preparation of the 11-sulphonamido compounds of Formula (I) wherein NR<SP>1</SP>R<SP>11</SP> is not monoalkylamino from the corresponding 11-amino compounds and the appropriate sulphonyl halide or sulphonic anhydride; (10) dealkylation of the products of process (9) by the method of (4) to give the corresponding 3- monoalkylaminopropyl compounds; (11) the preparation of compounds of the Formula (I) wherein A is alkyl and Z is acyloxy by acylation of the corresponding 11-ols, the starting material being an acid-addition salt if NR<SP>1</SP>R<SP>11</SP> is monoalkylamino; and (12) the preparation of the 11-hydrazono compounds of Formula (I) by reaction of the corresponding 11-ketones with hydrazine. Products containing 2 dissimilar substituents on the 11-carbon atom may be resolved by conventional methods. The 5,10-epoxydibenzocycloheptenes of the invention, which are stated to be anti-depressants, may be made up into pharmaceutical compositions for oral or parenteral administration with suitable carriers.