Zileuton, ABT-077, A-64077, Zyflo, Leutrol, -Drug Synthesis Database

【结构式】

【药物名称】Zileuton, ABT-077, A-64077, Zyflo, Leutrol

【化学名称】(±)-N-Hydroxy-N-[1-(benzothiophen-2-yl)ethyl]urea
　　　　　　(±)-N-Hydroxy-N-[1-(benzo[b]thien-2-yl)ethyl]urea
　　　　　　(±)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea

【CA登记号】111406-87-2

【分子式】C₁₁H₁₂N₂O₂S

【分子量】236.29449

【开发单位】Abbott (Originator)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, 5-Lipoxygenase Inhibitors, Leukotriene Synthesis Inhibitors

合成路线1 合成路线2

合成路线1

The synthesis of zileuton involved conventional synthetic procedures starting with 2-acetylbenzo[b]thiophene. Treatment of a solution of 2-acetylbenzo[b]thiophene (I) in ethanol/pyridine (1:1) with hydroxylamine hydrochloride at room temperature provided the corresponding oxime (II). To the oxime (II) dissolved in ethanol was added borane:pyridine complex followed by the dropwise addition of 20% HCl in ethanol to provide the hydroxylamine (III), isolated by extraction after neutralization of the acidic mixture. The hydroxylamine (III) was converted to zileuton by either heating with trimethylsilylisocyanate in dioxane or by reacting with KOCN and aqueous HCl.

参考文献中间体

【1】 Summers, J.B. Jr.; Gunn, B.P.; Brooks, D.W. (Abbott Laboratories Inc.); Indole, benzofuran, benzothiophene containing lipoxygenease inhibiting compounds. EP 0279263; JP 1988264456; US 4873259 .
【2】 Brooks, D.W.; Rubin, P.D.; Carter, G.W.; Dube, L.M.; Bell, R.L.; Zileuton. Drugs Fut 1993, 18, 7, 616.

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)	12947	1-(1-Benzothiophen-2-yl)-1-ethanone	22720-75-8	C₁₀H₈OS	详情	详情
(II)	12948	1-(1-Benzothiophen-2-yl)-1-ethanone oxime		C₁₀H₉NOS	详情	详情
(III)	12949	2-[1-(Hydroxyamino)ethyl]-1-benzothiophene; N-[1-(1-Benzothiophen-2-yl)ethyl]hydroxylamine		C₁₀H₁₁NOS	详情	详情

合成路线2

A new efficient synthesis of 2-acetylbenzothiophene (I), the key starting material for the previously reported synthesis of zileuton, has been described: Thiophenol (II) is dilithiated with butyllithium and tetramethylethylenediamine in cyclohexane to compound (III), which is then cyclized by successive treatments with DMF and chloroacetone (IV) in THF to afford (I) in high yield.

参考文献中间体

【1】 Brooks, D.W.; Basha, A.; Synthesis of the 5-lipoxygenase inhibitor zileuton from thiophenol. J Org Chem 1993, 58, 5, 1293.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	15288	1-Chloroacetone; Chloroacetone	78-95-5	C₃H₅ClO	详情	详情
(I)	12947	1-(1-Benzothiophen-2-yl)-1-ethanone	22720-75-8	C₁₀H₈OS	详情	详情
(II)	12951	Benzenethiol; Phenylmercaptan; Phenylhydrosulfide	108-98-5	C₆H₆S	详情	详情
(III)	12952	2-Lithio-thiophenol lithium salt		C₆H₄Li₂S	详情	详情

Extended Information