新产品编号:899085
Chemical Name: 2-[3-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]-7-methoxy-6-(5-oxazolyl)quinolin-4(1H)-one
CAS No. 371251-98-8 ((R)-isomer), 371251-99-9 ((S)-isomer), 371249-88-6 (undefined isomer)
项目整合开发状态: Biological Testing
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Oxidation of 4-nitro-2-methoxytoluene (I) by means of chromic anhydride and sulfuric acid in the presence of acetic anhydride gives rise to acylal (II),which is further hydrolyzed to aldehyde (III) under acidic conditions.Reaction of aldehyde (III) with tosylmethyl isocyanide produces the 5-aryl oxazole (IV).Reduction of the nitro group of (IV) by catalytic hydrogenation yields aniline (V).Then,electrophilic iodination of amine (V) with iodine and silver triflate furnishes the aryl iodide (VI).
合成路线:6-Bromo-1-indanone (VII) is reduced to alcohol (VIII) employing NaBH4.After chlorination of (VIII) with SOCl2,the resultant alkyl chloride (IX) is displaced by heating with ethanolic dimethylamine in a sealed vessel to produce the (dimethylamino)indan (X).Palladium-catalyzed coupling of aryl bromide (X) with trimethylsilyl acetylene (XI) furnishes the silyl acetylene (XII),which is then desilylated to (XIII) with Bu4NF in THF.Finally,condensation between acetylene (XIII),aryl iodide (VI) and carbon monoxide in the presence of palladium catalyst leads to the title quinolone derivative.(1,2)
📌 参考资料/链接：
参考文献标题:Heterocycles that are inhibitors of IMPDH enzyme
文献作者:Pitts,W.J.; Iwanowicz,E.J.; Dhar,T.G.M.; Gu,H.H.; Watterson,S.H.(Bristol-Myers Squibb Co.)
参考来源:EP 1276739; JP 2003531205; WO 0181340
📄 详细内容
合成路线:6-Bromo-1-indanone (VII) is reduced to alcohol (VIII) employing NaBH4.After chlorination of (VIII) with SOCl2,the resultant alkyl chloride (IX) is displaced by heating with ethanolic dimethylamine in a sealed vessel to produce the (dimethylamino)indan (X).Palladium-catalyzed coupling of aryl bromide (X) with trimethylsilyl acetylene (XI) furnishes the silyl acetylene (XII),which is then desilylated to (XIII) with Bu4NF in THF.Finally,condensation between acetylene (XIII),aryl iodide (VI) and carbon monoxide in the presence of palladium catalyst leads to the title quinolone derivative.(1,2)
参考文献标题:Quinolone-based IMPDH inhibitors: Introduction of basic residues on ring D and SAR of the corresponding mono,di and benzofused analogues
文献作者:Dhar,T.G.M.; Watterson,S.H.; Chen,P.; Shen,Z.; Gu,H.H.; Norris,D.; Carlsen,M.; Haslow,K.D.; Pitts,W.J.; Guo,J.; Chorba,J.; Fleener,C.A.; Rouleau,K.A.; Townsend,R.; Hollenbaugh,D.; Iwanowicz,E.J.
参考来源:Bioorg Med Chem Lett 2003,13(3),547