- On the Knorr synthesis of 6-bromo-4-methylquinolin-2(1H)-one
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In the course of our work on infectious diseases, we were led to prepare 6-bromo-2-chloro-4-methylquinoline as a starting material. Since surprisingly little has been reported in the literature, the two synthetic steps to this compound were investigated. The synthesis involves a condensation between -keto esters and 4-bromoaniline and the cyclization of the resulting anilides into 6-bromoquinolin-2(1H)-one, otherwise known as the Knorr reaction. The 1H NMR monitoring of the first step allowed us to optimize the conditions leading specifically to the anilide without the occurrence of the alternative crotonate. To illustrate the scope of our finding, few additional anilides featuring electron-attracting groups were prepared. The study of their cyclization revealed some unsuspected steric effect governing this second step. Aside from rectifying a few claims in this chemistry, this study led to a three-step preparation of 6-bromo-2-chloro-4-methylquinoline in 48% overall yield from 4-bromoaniline. Georg Thieme Verlag Stuttgart - New York.
- Wlodarczyk, Nicolas,Simenel, Catherine,Delepierre, Muriel,Barale, Jean-Christophe,Janin, Yves L.
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experimental part
p. 934 - 942
(2011/05/05)
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- Bicyclic androgen and progesterone receptor modulator compounds and methods
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The present invention is directed to compounds, pharmaceutical compositions, and methods for modulating processes mediated by AR and PR. More particularly, the invention relates to nonsteroidal compounds and compositions that are high affinity, high specificity agonists, partial agonists (i.e., partial activators and/or tissue-specific activators) and antagonists for AR and PR. Also provided are methods of making such compounds and pharmaceutical compositions, as well as critical intermediates used in their synthesis.
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