ORGN 770 |
| A five-step synthesis of ABT-116, a TRPV1 receptor antagonist is described. The key step of the synthesis involves a novel palladium catalyzed amidation reaction of 4-chloro-1-methylindazole 1 with the benzyl urea 2 to form unsymmetrically substituted urea ABT-116. 4-chloro-1-methylindazole 1 is prepared from readily available 2-chloro-6-fluoro-benzaldehyde by reacting it with excess methyl hydrazine to afford the desire indazole in good yield. Benzyl urea is prepared via a three-step sequence from 3-chloro-4-cyano-benzotrifluoride. Sonogashira coupling of 3-chloro-4-cyano-benzotrifluoride with 3,3-dimethylbut-1-yne is accomplished using Davephos ligand in triethylamine at 65oC with 95% yield. Hydrogenation of the Sonogashira product reduces the nitrile and alkyne group at same time. The resulting amine reacts with phenyl carbamate to form the desired benzyl urea 2 in excellent yield.
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Heterocycles and Aromatics, Asymmetric Reactions and Syntheses and Total Synthesis of Complex Molecules
7:00 PM-9:00 PM, Wednesday, August 19, 2009 Walter E. Washington Convention Center -- Ballroom C, Poster
Division of Organic Chemistry |
