【药物名称】FR-166124
化学结构式(Chemical Structure):
参考文献No.27426
标题:Pyrazolopyridine adenosine antagonists
作者:Akahane, A.; Nishimura, S.; Itani, H.; Durkin, K.P.M. (Fujisawa Pharmaceutical Co., Ltd.)
来源:EP 0737193; JP 1997507485; US 5773530; WO 9518128
合成路线图解说明:

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No.545756
标题:Discovery of FR166124, a novel water-soluble pyrazolo-[1,5-a]pyridine adenosine A1 receptor antagonist
作者:Kuroda, S.; Akahane, A.; Itani, H.; Nishimura, S.; Durkin, K.; Kinoshita, T.; Tenda, Y.; Sakane, K.
来源:Bioorg Med Chem Lett 1999,9(14),1979
合成路线图解说明:

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No.563510
标题:Process improvements in the production of a novel non-xanthine adenosine A1 receptopr antagonist. A "one-pot" horner-emmons isomerization reaction
作者:Zanka, A.; et al.
来源:Org Process Res Dev 1999,3(6),394
合成路线图解说明:

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.

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