- Chemical development of ZD9331: Synthesis of a bromomethylquinazolinone avoiding a nonselective radical bromination
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An efficient regiospecific synthesis of ZD9331 Pivaloyloxymethyl (POM) Bromide (4) has been accomplished via ZD9331 Quinacetate HCl (15) avoiding a nonselective bromination. The original route used a radical bromination on a substrate with three methyl groups, which generated a range of bromomethyl derived compounds that carried through to the final active pharmaceutical ingredient (API). A strategy, based on the Zinin reaction, was developed to synthesize the required bromomethyl compound in a regioselective manner. This approach was successfully scaled to manufacture a tonne of material.
- Bentley, Dagmar,Godfrey, Andrew A.,Warren, Kenneth E. H.
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- A [...] intermediate 2 - methyl - 4 - N - (2 - methyl benzoyl) benzoic acid
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The invention relates to a [...] intermediate 2 - methyl - 4 - N - (2 - methyl benzoyl) benzoic acid for the preparation of the new method, the method to 3 - methylaniline as the starting material, acetate acylation, cyano, cyano hydrolysis, the amidation reaction to obtain the intermediate 2 - methyl - 4 - N - (2 - methyl benzoyl) benzoic acid. The material of the invention is easy to obtain, mild reaction conditions, high yield, does not need special equipment, without the use of highly toxic or an expensive reagent, low cost, convenient to industrial production.
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Paragraph 0018
(2019/07/04)
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