Verfahren zur Herstellung von tricyclischen Verbindungen

• Main Authors: SPIEGELBERG,HANS,DR, KYBURZ,EMILIO,DR
• Format: Patent
• Language: German
• Published: 15.08.1973
• Edition: 1
• Subjects: AIR-CONDITIONING, AIR-HUMIDIFICATION, VENTILATION, USE OF AIRCURRENTS FOR SCREENING; BLASTING; HEATING; LIGHTING; MECHANICAL ENGINEERING; RANGES; VENTILATING; WEAPONS

1,236,712. Dibenzocycloheptene derivatives. F. HOFFMANN-LA ROCHE & CO. A.G. 13 March, 1969 [20 March, 1968], No. 13202/69. Heading C2C. The invention comprises compounds of the Formula (VII) wherein R is Cl or F, R 1 and R 2 each denotes H, Cl or F, R 3 denotes H, C 1-7 alkanoyl or benzoyl, which may be substituted, and X is the ethylene or vinylene group which can be substituted by Cl or Br and the dotted line can be hydrogenated, isomers thereof and acid addition salts; and compounds of the Formula (III) in which one of the symbols Y 1 and Y 2 denotes H and the other OH, and acid addition salts thereof. Compounds of Formula (VII) in which R 3 is H can be obtained by (a) oxidizing a compound of the Formula (II) (b) dehydrating a compound of the Formula (III), (c) treating with methylhydroxylamine a compound of one of the formulµ where Z denotes halogen or a substituted sulphonyloxy residue and A is the anion of an acid, or (d) saponifying a compound of Formula (VII) in which R 3 is a C 1-7 alkanoyl or benzoyl group, then, if desired, in optional sequence, isomers are isolated from an isomeric mixture, and the resulting base is converted to an acid addition salt. Compounds VII in which R 3 is C 1-7 alkanoyl or benzoyl, can be obtained, for example, by treating (II) with benzoyl peroxide, acetyl peroxide or acetyl benzoyl peroxide. Preparation of the following intermediates is also described (where DDCH denotes 10,11- dihydro - 5H - dibenzo[a,d]cycloheptene). 1-Chloro-DDCH-5-one is reacted with 1-chloro- 3-methoxypropane to yield 1-chloro-5-(3-methoxypropyl)-5-hydroxy DDCH which is refluxed with methanolic HCl forming 1-chloro- 5-(3-methoxypropylidene)-DDCH; the latter is reacted with BCl 3 to give 1-chloro-5-(3-chloropropylidene)-DDCH, which is reacted with methylamine to form 1-chloro-5-(3-methylaminopropylidene) - DDCH. 1 - Chloro-DDCH- 5-one is reacted with 3-dimethylamino-propylchloride giving 1 - chloro - 5 - hydroxy - 5 - (3- dimethylaminopropyl)-DDCH, which is then reacted with cyanogen bromide to form 1- chloro - 5 - (3 - N - cyano - N - methyl - aminopropyl)-DDCH; the latter is refluxed with cone. HCl to give 1.chloro.5.(3.methylamino. propyl)-DDCH. Pharmaceutical compositions having antidepressant activity comprise compounds of Formula (VII) in which R 3 is hydrogen, in association with a compatible pharmaceutical carrier, in forms suitable for enteral or parenteral administration.