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The synthesis of possible hydroxylated metabolites of 2‐chlorophenothiazine derivatives
Author(s) -
Zirnis Aija,
Suzuki Joseph K.,
Dickson Donald E.,
Laitar Robert A.,
Manian Albert A.
Publication year - 1977
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570140121
Subject(s) - chemistry , side chain , metabolite , iodide , chloride , chlorpromazine , perphenazine , stereochemistry , organic chemistry , biochemistry , pharmacology , medicine , polymer
The synthesis of 7‐hydroxy, 8‐hydroxy and 7,8‐dihydroxy prochlorperazines (3a) and per‐phenazines (3b) is reported. The parent ehlorophenothiazines were prepared analogously to previously reported chlorpromazine (3e) metabolite syntheses. The prochlorperazine side chain was introduced in one step using 1‐(3‐chloropropyl)‐4‐methylpiperazine and the perphenazine side chain in two steps, first reaction with 1‐bromo‐3‐chloropropane followed by reaction with 1‐piperazineethanol. The methoxymethyleneoxy O‐proteetive groups were removed under mild conditions using methanolic hydrogen chloride. The preparations of 7‐hydroxydesmethylprochlorperazine and 7‐hydroxychlorpromazine quaternary methyl iodide are also reported.