MOL-294
Chemical Name: cis-4-Hydroxy-4-(8-methyl-1,3-dioxo-2-phenyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl)-2-butynoic acid methyl ester
CAS No. 203455-50-9 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Molecumetics (Originator)
合成路线:Addition of methyl propiolate (I) to 2,4-hexadienal (II) using lithium hexamethyldisilazide afforded diene (III).Subsequent cycloaddition of (III) to 4-phenyl urazole (IV) in the presence of iodobenzene diacetate produced the corresponding triazolopyridazine as a diastereomeric mixture,from which the required cis isomer was isolated by flash chromatography.
📌 参考资料/链接：
参考文献标题:Use of beta-sheet mimetics as protease and kinase inhibitors and as inhibitors of transcription factors
文献作者:Eguchi,M.; Qabar,M.N.; Ferguson,M.D.; Babu,S.; Boatman,P.D.Jr.; McMillan,M.K.; Kahn,M.; Ogbu,C.O.; Lum,C.T.; Meara,J.P.; Kim,H.-O.; Urban,J.(Molecumetics Ltd.)
参考来源:US 6117896; WO 9805333
📄 详细内容
合成路线:Addition of methyl propiolate (I) to 2,4-hexadienal (II) using lithium hexamethyldisilazide afforded diene (III).Subsequent cycloaddition of (III) to 4-phenyl urazole (IV) in the presence of iodobenzene diacetate produced the corresponding triazolopyridazine as a diastereomeric mixture,from which the required cis isomer was isolated by flash chromatography.
合成路线:The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromobenzyl bromide (II) in the presence of n-butyllithium,followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III).Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V),which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI).Finally,Suzuki coupling of (VI) with 3-methoxybenzeneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.
合成路线:The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromo-2-fluorobenzyl bromide (II) in the presence of n-butyllithium,followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III).Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V),which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI).Finally,Suzuki coupling of (VI) with 5-butyl-2-thiopheneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.
参考文献标题:Synthesis and biological studies of a novel inhibitor of NF-kappaB
文献作者:McMillan,M.; Cudaback,E.; Misra-Press,A.; et al.
参考来源:217th ACS Natl Meet (March 21 1999,Anaheim) 1999,Abst MEDI 213