Hydrochloric Acid → 5-Chloro-5H-dibenzo[a,d][7]annulene

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Certain of these prior art methods are described in U.S. Pat. No. 3,372,196 of Edward L. Engelhardt and in a publication of Engelhardt et al., J. Med. Chem., 11, 326-332 (1968). One such typical method begins with 5H-dibenzo[a,d]cycloheptene-5-one and first converts the ketone to the corresponding 5-hydroxy compound by reduction with borohydride followed by treatment with dry hydrogen chloride to produce the corresponding 5-chloro-5H-dibenzo[a,d]cycloheptene. This compound is then coupled with a Grignard reagent derived from dimethylaminopropyl chloride to produce the desired N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-5-propylamine which is demethylated to the corresponding N-methyl derivative. Another method, disclosed in the above-mentioned patent, to prepare compounds of the type described involves the reaction of a 5H-dibenzo[a,d]cycloheptene-5-one with an alkoxypropyl magnesium halide to produce the corresponding 5-alkoxypropyl-5-hydroxy-5H-dibenzo[a,d]cycloheptene and reducing this compound using hydrogen iodide in acetic anhydride to produce a 5-(3-iodopropyl)-5H-dibenzo[a,d]cycloheptene in low yield. This compound is then reacted with ammonia or a lower alkyl or dialkyl amine to produce the corresponding 5-(3-aminopropyl, 3-alkylaminopropyl, or 3-dialkylaminopropyl)-5H-dibenzo[a,d]cycloheptene. Compounds of this type have tetrabenazine antagonist activity and are useful in the treatment of humans affected by depression as reported in the above-noted J. Med. Chem. article or as disclosed in the above-noted U.S. Pat. No. 3,372,196 of Engelhardt or are useful as intermediates in the preparation of such compounds.

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