【药物名称】GW-587270
化学结构式(Chemical Structure):
参考文献No.41171
标题:Morpholino ethers
作者:Bueno, J.M.; Chicharro Gonzalo, J.; Coteron, J.-M.; Cuevas, J.C.; Fiandor, J.M.; Mallo, A. (GlaxoSmithKline SA)
来源:EP 1077959; JP 2002514632; WO 9958512
合成路线图解说明:

Oxidative cleavage of 6-deoxy-beta-D-mannopyranosyl sordaricin (I) using sodium periodate furnished dialdehyde (II). Subsequent reductive amination of dialdehyde (II) gave rise to the morpholino derivative (III). Acidic hydrolysis of the ethylene ketal function of (III) provided aldehyde (IV). The carboxylic group was then protected as the benzhydryl ester (V) using diphenyl diazomethane. 2-Methylene-1,3-propanediol (VI) was converted to mono-tosylate (VII) by treatment with p-toluenesulfonyl chloride in the presence of dibutyltin oxide and N-methylimidazole. Subsequent hydroxyl group fluorination of (VII) by means of diethylaminosulfur trifluoride provided 2-(fluoromethyl)propenyl tosylate (VIII). Alkylation of the morpholine N of (V) with tosylate (VIII) gave adduct (IX). The benzhydryl ester of (IX) was finally cleaved to the title carboxylic acid by treatment with trifluoroacetic acid.

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