BMS-229724
4-[4-[2-[2-[双(4-氯苯基)甲氧基]乙基磺酰]乙氧基]苯基]-1,1,1-三氟丁烷-2-1Chemical Name: 4-[4-[2-[2-[Bis(4-chlorophenyl)methoxy]ethylsulfonyl]ethoxy]phenyl]-1,1,1-trifluorobutan-2-one
CAS No. 221914-85-8
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Condensation of 4,4'-dichlorobenzhydrol (I) with 2-bromoethanol (II) in the presence of sulfuric acid gave the bromopropyl ether (III),which was further condensed with 2-mercaptoethanol (IV),yielding thioether (V).Subsequent coupling of alcohol (V) with methyl 3-(4-hydroxyphenyl)propionate (VI) under Mitsunobu conditions furnished adduct (VII).Basic hydrolysis of the methyl ester function generated acid (VIII).After conversion of (VIII) to the corresponding acid chloride,its condensation with trifluoroacetic anhydride gave rise to the trifluoromethyl ketone (IX).The sulfide group of (X) was finally oxidized to the title sulfone using meta-chloroperbenzoic acid.
📌 参考资料/链接：
参考文献标题:Selective cPLA2 inhibitors
文献作者:Banville,J.; Burke,J.R.; Gai,Y.; Johnson,G.; Zusi,F.C.(Bristol-Myers Squibb Co.)
参考来源:EP 1140791; WO 9915129
📄 详细内容
合成路线:The hydrolysis of the known thioacetate (I) with NaOH in THF gives the thiol (II),which is condensed with 14C-labelled bromoacetic acid (III) by means of NaOH in water to yield the sulfanyl-acetic acid (IV).The reduction of (IV) with LiAlH4 in THF affords the sulfanylethanol derivative (V); which is condensed with 3-(4-hydroxyphenyl)propionic acid methyl ester (VI) by means of DEAD and PPh3 in toluene to provide the labelled aryl ether (VII).The hydrolysis of the ester group of (VII) by means of KOH in ethanol/water gives the propionic acid (VIII),which is converted into the trifluoromethyl ketone (IX) by reaction with oxalyl chloride,trifluoroacetic anhydride and pyridine in toluene/dichloromethane.Finally,the oxidation of the sulfanyl group of (IX) with MCPBA in dichloromethane affords the target labelled sulfone.
参考文献标题:Synthesis of carbon-14 labeled 4-[4-[2-[2-[bis(4-chlorophenyl)methoxy]ethylsulfonyl][1-14C]ethoxy]phenyl]-1,1,1-trifluoro-2-butanone
文献作者:Dischino,D.D.; Banville,J.; Remillard,R.
参考来源:J Label Compd Radiopharm 2003,46(2),167
产品链接: CAS No. 221914-85-8››