【药物名称】FR-167653
化学结构式(Chemical Structure):
参考文献No.24660
标题:Pyrazolitriazines with interleukin-1 and tumour necrosis factor inhibitory activity
作者:Kawai, Y.; Yamazaki, H.; Tanaka, H.; Oku, T. (Fujisawa Pharmaceutical Co., Ltd.)
来源:EP 0686156; JP 1996507056; WO 9419350
合成路线图解说明:

The lithium derivative of 4-picoline (I) was acylated with ethyl 4-fluorobenzoate (II) to afford ketone (III). Condensation of (III) with dimethylformamide dimethylacetal provided enaminone (IV) which was subsequently cyclized with hydroxylamine to give the diaryl isoxazole (V). Isoxazole ring opening in (V) under basic conditions led to keto nitrile (VI). Chlorination of (VI) by means of POCl3, followed by reaction with hydrazine, furnished the amino pyrazole (VII). The diazonium salt (VIII) prepared from amino pyrazole (VII) was then added to the phosphorane aldehyde (IX) to generate the pyrazolotriazine (X). Hydrogenation of the triazine ring of (X) employing NaBH3CN produced the tetrahydro pyrazolotriazine (XI). This was finally acylated by phenylglyoxylic acid (XII) to yield the target alpha-oxo amide.

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