FR-166124
Chemical Name: 2-[2-[6-Oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1,6-dihydropyridazin-1-yl]-1-cyclohexenyl]acetic acid
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线:This compound was prepared by two ways starting from 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (I).Alkylation of (I) with 2-chlorocyclohexanone (II) in the presence of NaH in DMF gave diketone (V).Alternatively,condensation of (I) with epoxycyclohexane and NaH in DMF at 127 C yielded the ketoalcohol (IV) as a mixture of cis and trans isomers,which were separated by column chromatography.The major trans isomer was then oxidized with pyridinium dichromate to the diketone (V).Reaction of this diketone with the sodium salt of triethyl phosphonoacetate (VI) in toluene at 100 C afforded a mixture of unsaturated esters (VII) and (VIII),which were subsequently submitted to hydrolysis with NaOH.Then,column chromatography of the mixture provided the desired endocyclic unsaturated acid.
📌 参考资料/链接：
参考文献标题:Pyrazolopyridine adenosine antagonists
文献作者:Akahane,A.; Nishimura,S.; Itani,H.; Durkin,K.P.M.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0737193; JP 1997507485; US 5773530; WO 9518128
📄 详细内容
合成路线:This compound was prepared by two ways starting from 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (I).Alkylation of (I) with 2-chlorocyclohexanone (II) in the presence of NaH in DMF gave diketone (V).Alternatively,condensation of (I) with epoxycyclohexane and NaH in DMF at 127 C yielded the ketoalcohol (IV) as a mixture of cis and trans isomers,which were separated by column chromatography.The major trans isomer was then oxidized with pyridinium dichromate to the diketone (V).Reaction of this diketone with the sodium salt of triethyl phosphonoacetate (VI) in toluene at 100 C afforded a mixture of unsaturated esters (VII) and (VIII),which were subsequently submitted to hydrolysis with NaOH.Then,column chromatography of the mixture provided the desired endocyclic unsaturated acid.
参考文献标题:Discovery of FR166124,a novel water-soluble pyrazolo-[1,5-a]pyridine adenosine A1 receptor antagonist
文献作者:Kuroda,S.; Akahane,A.; Itani,H.; Nishimura,S.; Durkin,K.; Kinoshita,T.; Tenda,Y.; Sakane,K.
参考来源:Bioorg Med Chem Lett 1999,9(14),1979
合成路线:This compound was prepared by two ways starting from 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (I).Alkylation of (I) with 2-chlorocyclohexanone (II) in the presence of NaH in DMF gave diketone (V).Alternatively,condensation of (I) with epoxycyclohexane and NaH in DMF at 127 C yielded the ketoalcohol (IV) as a mixture of cis and trans isomers,which were separated by column chromatography.The major trans isomer was then oxidized with pyridinium dichromate to the diketone (V).Reaction of this diketone with the sodium salt of triethyl phosphonoacetate (VI) in toluene at 100 C afforded a mixture of unsaturated esters (VII) and (VIII),which were subsequently submitted to hydrolysis with NaOH.Then,column chromatography of the mixture provided the desired endocyclic unsaturated acid.
参考文献标题:Process improvements in the production of a novel non-xanthine adenosine A1 receptopr antagonist.A "one-pot" horner-emmons isomerization reaction
文献作者:Zanka,A.; et al.
参考来源:Org Process Res Dev 1999,3(6),394