【药物名称】Isofezolac, LM-22102
化学结构式(Chemical Structure):
参考文献No.62050
标题:Isofezolac
作者:Casta馿r, J.; Arrigoni, Martelli, E.
来源:Drugs Fut 1980,5(1),21
合成路线图解说明:

The reaction of aniline (I) with ethyl bromoacetate (II) by means of triethylamine in benzene gives ethyl phenylaminoacetate (III), which is nitrosated with NaNO2 and HCl in water to yield ethyl N-nitrosophenylaminoacetate (IV). The reduction of (IV) with Zn in ethanol-water-acetic anhydride affords ethyl N1-phenylhydrazinoacetate (V), which is condensed with benzil (A) by means of HCl-sodium acetate in refluxing ethanol-water to yield ethyl alpha-benzoylbenzylidene-N1-phenylhydrazinoacetate (VI). The cyclization of (VI) by means of sodium ethoxide in refluxing ethanol gives 1,3,4-triphenylpyrazole-5-carboxylic acid (VII), which is reduced with LiAlH4 in ether-THF to produce 1,3,4-triphenyl-5-(hydroxymethyl)pyrazole (VIII). The reaction of (VIII) with SOCl2 in refluxing chloroform yields 1,3,4-triphenyl-5-(chloromethyl)pyrazole (IX), which by reaction with NaCN in hot DMSO is converted into 1,3,4-triphenylpyrazole-5-acetonitrile (X). Finally, this compound is hydrolyzed by means of NaOH in refluxing aqueous ethanol.

参考文献No.701397
标题:
作者:Gueremy, C.; Renault, C.
来源:US 3984431
合成路线图解说明:

The reaction of aniline (I) with ethyl bromoacetate (II) by means of triethylamine in benzene gives ethyl phenylaminoacetate (III), which is nitrosated with NaNO2 and HCl in water to yield ethyl N-nitrosophenylaminoacetate (IV). The reduction of (IV) with Zn in ethanol-water-acetic anhydride affords ethyl N1-phenylhydrazinoacetate (V), which is condensed with benzil (A) by means of HCl-sodium acetate in refluxing ethanol-water to yield ethyl alpha-benzoylbenzylidene-N1-phenylhydrazinoacetate (VI). The cyclization of (VI) by means of sodium ethoxide in refluxing ethanol gives 1,3,4-triphenylpyrazole-5-carboxylic acid (VII), which is reduced with LiAlH4 in ether-THF to produce 1,3,4-triphenyl-5-(hydroxymethyl)pyrazole (VIII). The reaction of (VIII) with SOCl2 in refluxing chloroform yields 1,3,4-triphenyl-5-(chloromethyl)pyrazole (IX), which by reaction with NaCN in hot DMSO is converted into 1,3,4-triphenylpyrazole-5-acetonitrile (X). Finally, this compound is hydrolyzed by means of NaOH in refluxing aqueous ethanol.

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