Method of synthesizing key intermediates for the production of camptothecin derivatives
AssigneeAvra Laboratories Pvt. Ltd
InventorsRamakrishna Rao, Venkata Rama Rao Alla
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Abstract
The present invention discloses a process for efficient production of 2-amino-5-hydroxypropiophenone corresponding to the AB ring part of camptothecin (CPT) skeleton, which is a key intermediate useful for the total synthesis of camptothecin analogs including 7-Ethyl-10-hydroxy camptothecin and novel intermediates thereof.
Claims21
A process for preparing 2-amino-5-hydroxypropiophenone to synthesize camptothecin analogs, wherein compound (13)
- is produced by dropping a Grignard reagent under an inert atmosphere to compound (12)
- wherein compound (14)
- is produced by mixing compound (13) with an oxidizing agent and stirring the mixture in a solvent;
- wherein compound (15)
- is produced by dropping a nitrating agent to compound (14);
- wherein compound (16)
- is produced by mixing compound (15), a metal hydroxide and an alcohol, and stirring the mixture;
- wherein compound (17)
- is produced by deprotection of compound (16), or by stirring a mixture of compound (15) and an aqueous base;
- wherein compound (11)
- is produced by reduction of compound (17) by mixing with a base and a reducing agent, and stirring the mixture in an aqueous alcoholic solution;
- and
- wherein X is a halogen, and R is hydrogen or a protective group which can be deprotected.
5-Fluoro-2-nitropropiophenone, a novel intermediate for the manufacture of camptothecin, prepared by mixing a nitrating agent with 5-fluoropropiophenone.
5-Alkoxy-2-nitropropiophenone, a novel intermediate for the manufacture of camptothecin, prepared by mixing compound (15),
- a metal hydroxide and alkanol, and stirring the mixture;
- wherein alkoxy is methoxy when alkanol is methanol, and alkoxy is ethoxy when alkanol is ethanol.
Dependencies are inferred from the claim text.