Abstract
AbstractClozapine has been demonstrated to bind covalently to proteins as a result of metabolic activation that has been proposed to be a precursor to the serious side effects including death that occur in a small percentage of the population. The covalent modification of proteins by clozapine has been studied by several groups and is well documented; therefore, the department of drug metabolism desired to use [14C]clozapine as a positive control for covalent binding assays. The preparation of [14C]clozapine was first conducted using a previous reported route and then using a new route that utilized [14C]carbonylation as the isotope incorporating step. While this route worked, it was not deemed superior to the previous route. However, this methodology proved quite effective in preparing C‐14 labeled dibenzothiazepine and dibenzoxapine ring systems. Copyright © 2010 John Wiley & Sons, Ltd.
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