SMP-114
Chemical Name: N2-[3-[1(S)-(2-Fluorobiphenyl-4-yl)ethyl]-5-isoxazolyl]-4-morpholinecarboxamidine hydrochloride
项目整合开发状态: Phase II
项目研究机构: Sumitomo Pharmaceuticals (Originator)
合成路线:The condensation of 2(S)-(2-fluorobiphenyl-4-yl)propionic acid (I) with tert-butyl cyanacetate (II) by means of lithium amide in THF gives lithium enolate (III),which is cyclized with hydroxylamine in aqueous DMF to yield the 5-aminoisoxazole (IV).Finally,this compound is condensed with morpholine-4-carbonitrile by means of lithium amide in toluene/tert-butanol to afford the target amidine.
📌 参考资料/链接：
参考文献标题:Isoxazole derivs.
文献作者:Ueno,Y.; Okada,S.; Nakatsuka,M.; Nishikaku,F.(Sumitomo Pharmaceuticals Co.,Ltd.)
参考来源:EP 0979226; JP 1999240873; US 6100260; WO 9847880
📄 详细内容
合成路线:The condensation of 2(S)-(2-fluorobiphenyl-4-yl)propionic acid (I) with tert-butyl cyanacetate (II) by means of lithium amide in THF gives lithium enolate (III),which is cyclized with hydroxylamine in aqueous DMF to yield the 5-aminoisoxazole (IV).Finally,this compound is condensed with morpholine-4-carbonitrile by means of lithium amide in toluene/tert-butanol to afford the target amidine.
参考文献标题:Novel disease modifying anti-rheumatic agents (DMARDs): Syntheses and SAR of 5-guanidinoisoxazoles
文献作者:Nakatsuka,M.; et al.
参考来源:222nd ACS Natl Meet (Aug 26 2001,Chicago) 2001,Abst MEDI 269