ethyl 2-(4-pyridinyl)acetate; Ethyl 4-pyridylacetate -Drug Synthesis Database

【结构式】

【分子编号】10849

【品名】ethyl 2-(4-pyridinyl)acetate; Ethyl 4-pyridylacetate

【CA登记号】54401-85-3

【分子式】C₉H₁₁NO₂

【分子量】165.19188

【元素组成】C 65.44% H 6.71% N 8.48% O 19.37%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

1) The reaction of 4-(chloromethyl)pyridine (I) with KCN in refluxing methanol gives 2-(4-pyridyl)acetonitrile (II), which is alkylated with ethyl iodide and sodium hydride in DMF, yielding 2-(4-pyridyl)butyronitrile (III). The condensation of (III) with acrylonitrile (IV) by means of Triton B in tert-butanol affords 2-cyano-2-(4-pyridyl)hexanenitrile (V), which is finally cyclized with concentrated H2SO4 in refluxing acetic acid. 2) The alkylation of 2-(4-pyridyl)acetic acid ethyl ester (VI) with ethyl iodide and potassium tert-butoxide gives 2-(4-pyridyl)butanoic acid ethyl ester (VII), which is condensed with acrylamide (VIII) by means of potassium tert-butoxide, yielding 4-carbamoyl-2-ethyl-2-(4-pyridyl)butanoic acid ethyl ester (IX). Finally, this compound is cyclized in the presence of potassium tert-butoxide. 3) The condensation of ester (VI) with acrylonitrile (IV) in the presence of Triton B gives 4-cyano-2-(4-pyridyl)butanoic acid ethyl ester (X), which is alkylated with ethyl iodide and lithium diisopropylamide yielding 4-cyano-2-ethyl-2-(4-pyridyl)butanoic acid ethyl ester (XI). Finally, this compound is cyclized with concentrated H2SO4 in refluxing acetic acid.

参考文献中间体

合成目标

【1】 Foster, A.B.; Jarman, M.; Taylor, G.N.; Kwan, C.-S. (Institute of Cancer Research); 2,6-Dioxopiperidine derivs., their preparation and pharmaceutical compsns. containing them. EP 0147121; GB 2151226; JP 1986500613; US 5071857; WO 8502618 .
【2】 Markson, A.J.; Boss, A.M.; Clissold, D.W.; Thickitt, C.P.; Mann, J.; A concise synthesis of racemic pyridoglutethimide and its resolution using chiral stationary phase HPLC. Tetrahedron 1989, 45, 18, 6011.
【3】 Jarman, M.; Griggs, L.J.; Wilman, D.E.V.; Rowlands, M.G.; Foster, A.B.; Leung, C.-S.; Analogues of 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione as selective inhibitors of aromatase: Derivatives with variable 1-alkyl and 3-alkyl substituents. J Med Chem 1987, 30, 9, 1550.
【4】 Sampson, P.; Taylor, G.N.; Leung, C.-S.; Rowlands, M.G.; Plevey, R.G.; Jarman, M.; Foster, A.B.; Analogues of animoglutethimide: Selective inhibition of aromatase. J Med Chem 1989, 28, 2, 200.

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)	10844	4-(Chloromethyl)pyridine	10445-91-7	C₆H₆ClN	详情	详情
(II)	10845	2-(4-Pyridinyl)acetonitrile		C₇H₆N₂	详情	详情
(III)	10846	2-(4-Pyridinyl)butanenitrile		C₉H₁₀N₂	详情	详情
(IV)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情
(V)	10848	2-Ethyl-2-(4-pyridinyl)pentanedinitrile		C₁₂H₁₃N₃	详情	详情
(VI)	10849	ethyl 2-(4-pyridinyl)acetate; Ethyl 4-pyridylacetate	54401-85-3	C₉H₁₁NO₂	详情	详情
(VII)	10850	ethyl 2-(4-pyridinyl)butanoate		C₁₁H₁₅NO₂	详情	详情
(VIII)	10851	Acrylamide	79-06-1	C₃H₅NO	详情	详情
(IX)	10852	ethyl 5-amino-2-ethyl-5-oxo-2-(4-pyridinyl)pentanoate		C₁₄H₂₀N₂O₃	详情	详情
(X)	10853	ethyl 4-cyano-2-(4-pyridinyl)butanoate		C₁₂H₁₄N₂O₂	详情	详情
(XI)	10854	ethyl 4-cyano-2-ethyl-2-(4-pyridinyl)butanoate		C₁₄H₁₈N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Knoevenagel condensation of aldehyde (X) with ethyl pyridylacetate (XI) in the presence of Ac2O leads to the unsaturated ester (XII), which is finally submitted to saponification with ethanolic NaOH to furnish the corresponding carboxylic acid.

参考文献中间体

合成目标

【1】 De Nanteuil, G.; Lila-Ambroise, C.; Rupin, A.; Vallez, M.-O.; Verbeuren, T.J.; New fibrinolytic agents: Benzothiophene derivatives as inhibitors of the t-PA-PAI-1 complex formation. Bioorg Med Chem Lett 2003, 13, 10, 1705.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	64854	3-(4-chlorophenoxy)-5,6-bis{[4-(phenylsulfanyl)benzyl]oxy}-1-benzothiophene-2-carbaldehyde		C₄₁H₂₉ClO₄S₃	详情	详情
(XI)	10849	ethyl 2-(4-pyridinyl)acetate; Ethyl 4-pyridylacetate	54401-85-3	C₉H₁₁NO₂	详情	详情
(XII)	64855	ethyl (E)-3-(3-(4-chlorophenoxy)-5,6-bis{[4-(phenylsulfanyl)benzyl]oxy}-1-benzothiophen-2-yl)-2-(4-pyridinyl)-2-propenoate		C₅₀H₃₈ClNO₅S₃	详情	详情

Extended Information