ORGN 741 |
| We previously reported that a 7-phenylaminothieno[3,2-b]pyridine-6-carbonitrile analog was a more potent Src kinase inhibitor than the corresponding 4-phenylaminothieno[2,3-b] isomer. In studying these two bicyclic cores as templates for the inhibition of a different kinase, improved activity was observed with the [2,3-b] isomer. To facilitate the preparation of these analogs, an improved route to a key intermediate, 4-chloro-2-iodothieno[2,3-b]pyridine-5-carbonitrile (1), was required. In our original preparation of 1, 2-nitrothiophene was converted in 3 steps to ethyl 4-chlorothieno[2,3-b]pyridine-5-carboxylate, with an additional 4 steps being needed to obtain the desired product. We report here a 5 step synthesis of 1 from a commercially available starting material that provides 1 in an overall yield of 48%. Optimization of this route and the synthesis of various C-3 substituted analogs will also be described.
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Combinatorial, Parallel and Process Chemistry, Heterocycles, Aromatics, New Reactions and Methodology
8:00 PM-10:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Organic Chemistry |
