ethyl 2-[2-[6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinyl]-1-cyclohexen-1-yl]acetate -Drug Synthesis Database

【结构式】

【分子编号】17991

【品名】ethyl 2-[2-[6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinyl]-1-cyclohexen-1-yl]acetate

【CA登记号】

【分子式】C₂₇H₂₆N₄O₃

【分子量】454.5286

【元素组成】C 71.35% H 5.77% N 12.33% O 10.56%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VIII)

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.

参考文献中间体

合成目标

【1】 Tenda, Y.; Kinoshita, T.; Sakane, K.; Nishimura, S.; Akahane, A.; Durkin, K.; Kuroda, S.; Discovery of FR166124, a novel water-soluble pyrazolo-[1,5-a]pyridine adenosine A1 receptor antagonist. Bioorg Med Chem Lett 1999, 9, 14, 1979.
【2】 Akahane, A.; Nishimura, S.; Itani, H.; Durkin, K.P.M. (Fujisawa Pharmaceutical Co., Ltd.); Pyrazolopyridine adenosine antagonists. EP 0737193; JP 1997507485; US 5773530; WO 9518128 .
【3】 Zanka, A.; et al.; Process improvements in the production of a novel non-xanthine adenosine A1 receptopr antagonist. A "one-pot" horner-emmons isomerization reaction. Org Process Res Dev 1999, 3, 6, 394.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	17984	6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone		C₁₇H₁₂N₄O	详情	详情
(II)	17985	2-Chlorocyclohexanone	822-87-7	C₆H₉ClO	详情	详情
(III)	17986	7-oxabicyclo[4.1.0]heptane; cyclohexene oxide	286-20-4	C₆H₁₀O	详情	详情
(IV)	17987	2-(2-hydroxycyclohexyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone		C₂₃H₂₂N₄O₂	详情	详情
(V)	17988	2-(2-oxocyclohexyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone		C₂₃H₂₀N₄O₂	详情	详情
(VI)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(VII)	17990	ethyl 2-[2-[6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinyl]cyclohexylidene]acetate		C₂₇H₂₆N₄O₃	详情	详情
(VIII)	17991	ethyl 2-[2-[6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)-pyridazinyl]-1-cyclohexen-1-yl]acetate		C₂₇H₂₆N₄O₃	详情	详情

Extended Information