【药物名称】DNK-333, DNK-333A
化学结构式(Chemical Structure):
参考文献No.35958
标题:Acylaminoalkenylene-amide derivs. as NK1 and NK2 antagonists
作者:Gerspacher, M.; Von Sprecher, A.; Mah, R.; Roggo, S.; Stutz, S. (Novartis AG)
来源:EP 0923550; JP 2001503387; US 6319917; WO 9807694
合成路线图解说明:

(3,4-Dichlorophenyl)alanine methyl ester (I) was converted to the N-Boc amino ester (II), which was subsequently alkylated with iodomethane in the presence of Ag2O, yielding the N-methyl derivative (III). Partial reduction of the ester group of (III) to the aldehyde (IV) was carried out using DIBAL in toluene at -78 C. Horner-Emmons reaction of aldehyde (IV) with triethyl phosphonoacetate (V) furnished the arylpentenoate ester (VI), which was further hydrolyzed to acid (VII) with LiOH. Coupling of acid (VII) with D-3-amino-epsilon-caprolactam (VIII) gave rise to amide (IX). The N-Boc group of (IX) was removed by treatment with trifluoroacetic acid, and the resulting amine (X) was finally acylated with 3,5-bis(trifluoromethyl)benzoyl chloride to produce the target amide.

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