新产品编号:810493
Chemical Name: 3-(4-Chlorophenyl)-3-[3-(3-guanidinobenzoyl)carbazoylamino]propionic acid trifluoroacetate
CAS No. 320727-84-2 (free base)
项目整合开发状态: Biological Testing
项目研究机构: Merck KGaA (Originator)
合成路线:The beta-amino acid (II) was prepared by Knoevenagel condensation of 4-chlorobenzaldehyde (I) with malonic acid in the presence of ammonium acetate.After protection of the amino group of (II) with Fmoc-Cl,the protected amino acid (III) was attached to the trityl chloride polystyrol resin,yielding the amino acid-bound resin (IV).The Fmoc group of (IV) was then removed using piperidine in DMF to afford (V).N-Fmoc-hydrazine (VI) was carbonylated with phosgene to obtain the oxadiazolone (VII).This was condensed with the amino resin (V) producing adduct (VIII).Deprotection of the Fmoc group of (VIII),followed by coupling with N-Fmoc-3-aminobenzoic acid (IX),furnished (X).After a new deprotection of (X) with piperidine in DMF,the guanidino group was introduced by condensation with N,N'-bis-Boc-1-guanylpyrazole to give (XI).Finally,deprotection and cleavage of the resin adduct (XI) was carried out with trifluoroacetic acid in the presence of triisopropylsilane.
📌 参考资料/链接：
参考文献标题:Diacylhydrazine derivs.
文献作者:Sulyok,G.; Kessler,H.; Holzemann,G.; Goodman,S.; Gibson,C.(Merck Patent GmbH)
参考来源:DE 19932796; WO 0105753
📄 详细内容
合成路线:The beta-amino acid (II) was prepared by Knoevenagel condensation of 4-chlorobenzaldehyde (I) with malonic acid in the presence of ammonium acetate.After protection of the amino group of (II) with Fmoc-Cl,the protected amino acid (III) was attached to the trityl chloride polystyrol resin,yielding the amino acid-bound resin (IV).The Fmoc group of (IV) was then removed using piperidine in DMF to afford (V).N-Fmoc-hydrazine (VI) was carbonylated with phosgene to obtain the oxadiazolone (VII).This was condensed with the amino resin (V) producing adduct (VIII).Deprotection of the Fmoc group of (VIII),followed by coupling with N-Fmoc-3-aminobenzoic acid (IX),furnished (X).After a new deprotection of (X) with piperidine in DMF,the guanidino group was introduced by condensation with N,N'-bis-Boc-1-guanylpyrazole to give (XI).Finally,deprotection and cleavage of the resin adduct (XI) was carried out with trifluoroacetic acid in the presence of triisopropylsilane.
参考文献标题:Solid-phase synthesis of a nonpeptide RGD mimetic library: New selective alphavbeta3 integrin antagonists
文献作者:Sulyok,G.A.G.; Gibson,C.; Goodman,S.L.; Holzemann,G.; Wiesner,M.; Kessler,H.
参考来源:J Med Chem 2001,44(12),1938