【药物名称】
化学结构式(Chemical Structure):
参考文献No.541849
标题:2-Heterosubstituted-3-(4-methylsulfonyl)phenyl-5-trifluromethyl pyridines as selective and orally active cyclooxygenase-2 inhibitors
作者:Dube, D.; Brideau, C.; Deschenes, D.; Fortin, R.; Friesen, R.W.; Gordon, R.; Girard, Y.; Riendeau, D.; Savoie, C.; Chan, C.C.
来源:Bioorg Med Chem Lett 1999,9(12),1715
合成路线图解说明:

Methyl (S)-lactate (I) was converted to chloride (II) by treatment with SOCl2. Subsequent displacement in (II) by cesium thioacetate produced thioester (III). Reduction of the ester group of (III) with concomitant thioester cleavage by means of LiAlH4 in cold THF furnished mercaptoalcohol (IV).

合成路线图解说明:

Bromination of 2-amino-5-trifluoromethylpyridine (V) in AcOH provided bromopyridine (VI), which was submitted to a Suzuki coupling with 4-(methylthio)benzeneboronic acid (VII) yielding the phenylpyridine derivative (VIII). Oxidation of the methylthio group of (VIII) to the corresponding sulfone (IX) was carried out by treatment with N-methylmorpholine-N-oxide in the presence of OsO4. Diazotization of the amino group of (IX) generated the pyridone (X), and further chlorination employing POCl3 provided chloropyridine (XI). Finally, condensation of (XI) with (S)-2-mercaptopropanol (IV) yielded the title compound.

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