Clomacran

Clomacran is an antipsychotic drug of the dihydroacridine class, developed in the 1970s by the pharmaceutical company Smith, Kline & French (now GlaxoSmithKline) under the brand names Devryl and Olaxin.

It was used to treat schizophrenia in the 70s. It was withdrawn from the market in the UK, due to liver toxicity, in 1982.

Synthesis


The first step involves FGI of 3-chloro-N,N-dimethylpropylamine Fb: [109-54-6] (2) into the Grignard reagent, i.e. (3-(Dimethylamino)propyl)magnesium chloride [19070-16-7] ([154034-91-0]). The Grignard reaction with 2-chloroacridone [7497-52-1] (1) affords the tertiary carbinol (3). Dehydration by means of acid or simply heat gives the corresponding olefin (4). Catalytic reduction completes the synthesis of (5).