【药物名称】
化学结构式(Chemical Structure):
参考文献No.38369
标题:Diphenyl oxadiazolones as potassium channel modulators
作者:Meanwell, N.A.; Starrett, J.E. Jr.; Hewawasam, P.; Romine, J.L.; Martin, S.W.; Gribkoff, V.K. (Bristol-Myers Squibb Co.)
来源:JP 2000516925; US 5869509; WO 9804135
合成路线图解说明:

4-Bromobenzotrifluoride (I) is converted to the corresponding Grignard reagent (II), which undergoes addition to diethyl oxalate, yielding keto ester (III). Subsequent saponification of ester (III) gives the phenylglyoxylic acid derivative (IV). Condensation of (IV) with 5-chloro-2-methoxyphenylhydrazine (V) affords the aryl hydrazone (VI). Curtius rearrangement of the carboxyl moiety of (VI) by means of diphenylphosphoryl azide generates the corresponding isocyanate, which spontaneously cyclizes to the triazolone (VII). Methyl ether cleavage in (VII) with boron tribromide gives rise to the title phenol derivative.

合成路线图解说明:

Acylation of 5-chloroanisidine (I) with 3,5-bis(trifluoromethyl)benzoyl chloride (II) affords benzamide (III). Treatment of amide (III) with PCl5, followed by reaction of the intermediate iminoyl chloride with hydrazine in THF generates the amidrazone (IV). Cyclization of (IV) with carbonyl diimidazole leads to triazolone (V). Finally, methyl ether cleavage in (V) employing pyridine hydrochloride at 225 C provides the target phenol compound.

参考文献No.668138
标题:The synthesis and structure-activity relationships of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones: A new class of calcium-dependent, large conductance, potassium (maxi-K) channel opener targeted for urge urinary incontinence
作者:Hewawasan, P.; Erway, M.; Thalody, G.; Weiner, H.; Boissard, C.G.; Gribkoff, V.K.; Meanwell, N.A.; Lodge, N.J.; Starrett, J.E. Jr.
来源:Bioorg Med Chem Lett 2002,12(7),1117
合成路线图解说明:

4-Bromobenzotrifluoride (I) is converted to the corresponding Grignard reagent (II), which undergoes addition to diethyl oxalate, yielding keto ester (III). Subsequent saponification of ester (III) gives the phenylglyoxylic acid derivative (IV). Condensation of (IV) with 5-chloro-2-methoxyphenylhydrazine (V) affords the aryl hydrazone (VI). Curtius rearrangement of the carboxyl moiety of (VI) by means of diphenylphosphoryl azide generates the corresponding isocyanate, which spontaneously cyclizes to the triazolone (VII). Methyl ether cleavage in (VII) with boron tribromide gives rise to the title phenol derivative.

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