Patent GB-1274265-A (GB)
Title: Dibenzocycloheptene derivatives
IPC: C07C291/04
Filed: 1969-05-01
Abstract: 1,274,265. 1,5 - Disubstituted - dibenzocycloheptenes. F. HOFFMANN-LA ROCHE & CO. A.G. 1 May, 1969 [3 May, 1968], No. 28708/71. Divided out of 1,274,261. Heading C2C. Novel compounds of Formula I wherein the dotted bonds can be hydrogenated, R<SP>1</SP> represents a methyl or ketalized acetyl (as hereinafter defined) group and A represents an amino, N - hydroxy - N - methyl - amino or N- benzyl - N - methyl - amino group or, when an exocyclic single-bond is present in the 5-position, an N - methyl - N - acylamino or N - methyl- N-(esterified carboxyl) group; (the term " ketalized acetyl " group is used herein to mean an acetyl group ketalized with an alkanol or alkylene glycol containing up to 7 carbon atoms) are prepared by one of the following methods: Those derivatives which carry a 3-aminopropylidene chain in the 5-position can be prepared by replacing the keto group of a corresponding 5H - dibenzo[a,d]cyclohepten- 5 - one or 10,11- dihydro - 5H - dibenzo[a,d]cyclohepten - 5 - one by an ethylidene group (e.g. by means of a Grignard reaction), halogenating the product obtained, treating the resulting halide with a nitrile and reducing the nitrile obtained with lithium aluminium hydride. Where the nitrile carries a methyl group in the 1-position, the reduction can be carried out using catalytically activated hydrogen, there being obtained a derivative of Formula I in which R<SP>1</SP> represents a methyl group and in which a 3-aminopropyl group is present in the 5-position. Compounds of Formula I which carry a 3-amino-propyl or 3-aminopropylidene group in the 5-position are also prepared by treating a compound of the general formula wherein R<SP>1</SP> and the dotted bonds have the significance given earlier and Z represents a halogen atom or a substituted-sulfonyloxy group, with potassium phthalimide and reacting the product obtained with hydrazine. Compounds which carry a 3-aminopropyl group in the 5-position are prepared by reacting a compound of formula wherein R<SP>1</SP> and the dotted bonds have the significance given earlier and T represents an alkali metal atom, with acrylonitrile and then reducing the resulting nitrile. Compounds of Formula I which carry an N-hydroxy substituent on the chain at the 3-position are prepared as follows: 1 -(Methyl or ketalized acetyl)- 5H - dibenzo[a,d]cyclohepten-5-one or the corresponding 10,11-dihydro compound is reacted with a N-methyl-N-benzylaminopropyl magnesium halide. After hydrolysis of the resulting product (e.g. with saturated ammonium chloride solution), the 5-carbinol obtained is reacted with chloroformic acid ethyl ester. The resulting 5 - hydroxy - 5 - [3 - (N - methyl-N- carbethoxyamino)-propyl] compound is then hydrolysed in an alkaline medium. A decarboxylation thereby occurs and there is formed the corresponding 5-hydroxy-5-(3-methylaminopropyl) compound. Where such a compound carries a methyl group in the 1-position of the ring, it can be reduced to the corresponding 5-(3-methylaminopropyl) compound by treatment with catalytically activated hydrogen. Compounds of Formula I wherein A is N-benzyl- N-methylamino are prepared by reaction of N-methyl benzylamine with either of compounds of formulµ wherein A is an anion.