PG-766969
Chemical Name: N-[3-[4-[1-(Ethoxymethyl)-4-(4-fluorophenyl)-1H-1,2,3-triazol-5-yl]pyrimidin-2-yloxy]phenyl]acetamide
CAS No. 474513-10-5
项目整合开发状态: Preclinical
项目研究机构: Procter & Gamble (Originator)
合成路线:4-Fluorophenylacetylene (I) is coupled to 4-chloro-2-(methylsulfanyl)pyrimidine (II) by means of Pd(PPh3)2Cl2 and CuI to furnish the diaryl acetylene (III).Subsequent condensation of acetylene (III) with sodium azide in hot DMA leads to triazole (IV).Alkylation of (IV) with chloromethyl ethyl ether gives rise to the three possible N-alkylated triazoles,which can be separated by means of preparative HPLC (1,2).The desired regioisomer (V) is then oxidized to sulfoxide (VI) employing m-chloroperbenzoic acid (1).Alternatively,oxone? oxidation of (V) produces the corresponding sulfone (VII) (1,2).Finally,condensation of either sulfoxide (VI) or sulfone (VII) with the sodium salt of m-(acetylamino)phenol (VIII) provides the title compound (1,2).
📌 参考资料/链接：
参考文献标题:Triazole cpds.useful in treating diseases associated with unwanted cytokine activity
文献作者:De,B.; Natchus,M.G.; Blass,B.E.; Tullis,J.S.; Van Rens,J.C.; Clark,M.P.(The Procter & Gamble Co.)
参考来源:EP 1383759; WO 0288108
📄 详细内容
合成路线:4-Fluorophenylacetylene (I) is coupled to 4-chloro-2-(methylsulfanyl)pyrimidine (II) by means of Pd(PPh3)2Cl2 and CuI to furnish the diaryl acetylene (III).Subsequent condensation of acetylene (III) with sodium azide in hot DMA leads to triazole (IV).Alkylation of (IV) with chloromethyl ethyl ether gives rise to the three possible N-alkylated triazoles,which can be separated by means of preparative HPLC (1,2).The desired regioisomer (V) is then oxidized to sulfoxide (VI) employing m-chloroperbenzoic acid (1).Alternatively,oxone? oxidation of (V) produces the corresponding sulfone (VII) (1,2).Finally,condensation of either sulfoxide (VI) or sulfone (VII) with the sodium salt of m-(acetylamino)phenol (VIII) provides the title compound (1,2).
参考文献标题:Development of 1,2,3-triazole based inhibitors of tumor necrosis factor alpha (TNF-alpha) production
文献作者:Van Rens,J.C.; Clark,M.P.; Tullis,J.S.; Natchus,M.G.; De,B.; Hsieh,L.; Janusz,M.J.
参考来源:225th ACS Natl Meet (March 23 2003,New Orleans) 2003,Abst MEDI 259