【药物名称】
化学结构式(Chemical Structure):
参考文献No.713308
标题:Imidazo[4,5-b]pyridines as corticotropin releasing factor receptor ligands
作者:Arvanitis, A.G.; Rescinito, J.T.; Arnold, C.R.; Wilde, R.G.; Cain, G.A.; Sun, J.H.; Yan, J.-S.; Teleha, C.A.; Fitzgerald, L.W.; McElroy, J.; Zaczek, R.; Hartig, P.R.; Grossman, S.; Arneric, S.P.; Gilligan, P.J.; Olson, R.E.; Robertson, D.W.
来源:Bioorg Med Chem Lett 2003,13(1),125
合成路线图解说明:

Nitration of 2,4-dihydroxypyridine (I) affords the 3-nitro derivative (II). Selective chlorination of the 4-hydroxy group of (II) is accomplished by treatment of the cycloheptylamine salt of (II) with POCl3 to furnish 4-chloro-2-hydroxy-3-nitropyridine (III). The 2-hydroxy group of (III) is then protected as the benzyl ether (IV) using benzyl bromide in the presence of silver carbonate. Suzuki coupling of protected chloropyridine (IV) with 2-chloro-4-(difluoromethoxy)phenylboronic acid (V) leads to the phenylpyridine derivative (VI). The O-benzyl group of (VI) is then removed with trifluoroacetic acid, and the resultant 2-hydroxypyridine (VII) is further chlorinated by means of POCl3, yielding (VIII). Displacement of the 2-chloro substituent of (VIII) with 1-cyclobutylethylamine (IX) in refluxing acetonitrile furnishes the 2-amino-3-nitropyridine (X). Subsequent nitro group reduction in (X) employing sodium dithionite and ammonium hydroxide leads to diamine (XI). This is finally cyclized to the desired imidazopyridine upon heating at reflux with propionic acid.

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