L-784506-药物合成数据库

【药物名称】L-784506

化学结构式(Chemical Structure):

参考文献No.	34771
标题:	Pyridinyl-2-cyclopenten-1-ones as selective cyclooxygenase-2 inhibitors
作者:	Black, C.; Hughes, G.; Wang, Z. (Merck Frosst Canada Inc.)
来源:	EP 0900201; JP 2000509032; US 5922742; WO 9740012

合成路线图解说明: 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.

参考文献No.	537451
标题:	2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors
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.
来源:	J Med Chem 1999,42(7),1274

合成路线图解说明: 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.

合成路线图解说明: 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).