合成路线:The title sulfone derivative is prepared by two alternative methods.Addition of sulfur to the lithio derivative of 5-chloro-3-methylbenzofuran (I) affords thiol (II).Further condensation of (II) with 3-chloro-6-methoxypyridazine (III) yields sulfide (IV).Acidic hydrolysis of methoxypyridazine (IV) leads to pyridazinone (V).The sulfide group of (V) is finally oxidized to the required sulfone employing an AcOH solution of peracetic acid.(1,2)
合成路线:Alternatively,3-chloro-6-methoxypyridazine (VI) is converted into the pyridazine thiol (VII) via reaction with thiourea in butanone.Oxidation of thiol (VII) with chlorine in the presence of potassium bifluoride leads to 4-methoxypyridazine-3-sulfonyl fluoride (VIII) (3).The lithio derivative of 5-chloro-3-methylbenzofuran (I) is then condensed with sulfonyl fluoride (VIII) to produce sulfone (IX).Finally,acidic hydrolysis of the methoxypyridazine group of (IX) gives rise to the corresponding pyridazinone compound (1-3).
参考文献标题:Pyridazinone aldose reductase inhibitors
文献作者:Mylari,B.L.(Pfizer Products Inc.)
参考来源:US 2002143017; US 6579879; WO 0279198
合成路线:Alternatively,3-chloro-6-methoxypyridazine (VI) is converted into the pyridazine thiol (VII) via reaction with thiourea in butanone.Oxidation of thiol (VII) with chlorine in the presence of potassium bifluoride leads to 4-methoxypyridazine-3-sulfonyl fluoride (VIII) (3).The lithio derivative of 5-chloro-3-methylbenzofuran (I) is then condensed with sulfonyl fluoride (VIII) to produce sulfone (IX).Finally,acidic hydrolysis of the methoxypyridazine group of (IX) gives rise to the corresponding pyridazinone compound (1-3).
参考文献标题:A highly selective,non-hydantoin,non-carboxylic acid inhibitor of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2-H-pyridazin-3-one
文献作者:Mylari,B.L.; Armento,S.J.; Beebe,D.A.; Conn,E.L.; Coutcher,J.B.; Dina,M.S.; O'Gorman,M.T.; Linhares,M.C.; Martin,W.H.; Oates,P.J.; Tess,D.A.; Withbroe,G.J.; Zembrowski,W.J.
参考来源:J Med Chem 2003,46(12),2283
产品链接: CAS No. 463976-07-0››