L-784506
3-[4-(甲基磺酰)苯基]-2-(3-吡啶)-2-环戊烯-1-酮Chemical Name: 3-[4-(Methylsulfonyl)phenyl]-2-(3-pyridyl)-2-cyclopenten-1-one
CAS No. 190966-40-6, 198985-43-2 (hydrochloride), 198985-44-3 (methanesulfonate)
项目整合开发状态: Preclinical
项目研究机构: Merck Frosst (Originator)
合成路线:The bromination of 3-ethoxy-2-cyclopenten-1-one (I) with Br2 and triethylamine in chloroform gives the 2-bromo derivative (II),which is condensed with 4-bromothioanisole (III) by means of BuLi in THF yielding 2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one (IV).The oxidation of (IV) with Na2WO4 and H2O2 affords the corresponding sulfone (V),which is finally condensed with lithium diisopropyl 3-pyridylboronate (VII) or the corresponding dimethyl ester (VIII) by means of tris(dibenzylideneacetone)dipalladium (III) (Pd2(dba)3) and triphenylphosphine in toluene/propanol/water.The lithium boronates (VII) and (VIII) have been obtained by reaction of 3-bromopyridine (VI) with triisopropyl borate or trimethyl borate and BuLi in ethyl ether.
📌 参考资料/链接：
参考文献标题:Pyridinyl-2-cyclopenten-1-ones as selective cyclooxygenase-2 inhibitors
文献作者:Black,C.; Hughes,G.; Wang,Z.(Merck Frosst Canada Inc.)
参考来源:EP 0900201; JP 2000509032; US 5922742; WO 9740012
📄 详细内容
合成路线:The bromination of 3-ethoxy-2-cyclopenten-1-one (I) with Br2 and triethylamine in chloroform gives the 2-bromo derivative (II),which is condensed with 4-bromothioanisole (III) by means of BuLi in THF yielding 2-bromo-3-[4-(methylsulfanyl)phenyl]-2-cyclopenten-1-one (IV).The oxidation of (IV) with Na2WO4 and H2O2 affords the corresponding sulfone (V),which is finally condensed with lithium diisopropyl 3-pyridylboronate (VII) or the corresponding dimethyl ester (VIII) by means of tris(dibenzylideneacetone)dipalladium (III) (Pd2(dba)3) and triphenylphosphine in toluene/propanol/water.The lithium boronates (VII) and (VIII) have been obtained by reaction of 3-bromopyridine (VI) with triisopropyl borate or trimethyl borate and BuLi in ethyl ether.
合成路线:The bromination of 3-ethoxy-2-cyclopentenone (XI) gives the 2-bromo derivative (XII),which is condensed with the aryl lithium (V) as before yielding the tertiary alcohol (XIII).Then (XIII) was submitted to an acid rearrangement to provide 2-bromo-3-[4-(sulfanylmethyl)phenyl]-2-cyclopentenone (IX),already obtained in the preceding approaches.The synthetic approaches can also be performed with the arylmagnesium analogue of lithium derivative (V).
参考文献标题:2,3-Diarylcyclopentenones as orally active,highly selective cyclooxygenase-2 inhibitors
文献作者:Black,W.C.; Brideau,C.; Chan,C.C.; Charleson,S.; Chaure,N.; Claveau,D.; Ethier,D.; Gordon,R.; Greig,G.; Guay,J.; Hughes,G.; Jolicoeur,P.; Leblanc,Y.; Nicoll-Griffith,D.; Ouimet,N.; Riendeau,D.; Visco,D.; Wang,Z.; Xu,L.; Prasit,P.
参考来源:J Med Chem 1999,42(7),1274
产品链接: CAS No. 190966-40-6››