Abbott-49816, A-49816, -Drug Synthesis Database

【结构式】

【药物名称】Abbott-49816, A-49816

【化学名称】Ethyl [2,3-dichloro-4-(3-aminomethyl-4-hydroxybenzoyl)phenoxy]acetate hydrochloride

【CA登记号】78235-46-8, 78235-72-0 (free base)

【分子式】C₁₈H₁₈Cl₃NO₅

【分子量】434.70686

【开发单位】Abbott (Originator)

【药理作用】Diuretics, RENAL-UROLOGIC DRUGS

合成路线1

Friedel-Crafts acylation of 2,3-dichlorophenetole with 4-methoxybenzoyl chloride gives the substituted benzophenone (I). Selective cleavage of the ethyl ether in (I) with AlCl3 produces phenol (II). Alkylation of (II) with ethyl bromoacetate is followed by heating with 48% HBr to give the phenoxyacetic acid derivative (III). Amidomethylation of (III) using the Tscherniac-Einhorn procedure gives (IV), which affords A-49816 after hydrolysis with HCl/EtOH.

参考文献中间体

【1】 Plattner, J.J.; Horrom, B.W.; Dodge, P.W.; Ours, C.W.; Lee, C.-M.; Pernet, A.G.; El Masry, S.E.; Smital, J.R.; Bunnell, P.R.; [(Aminomethyl)aryloxy]acetic acid esters. A new cl. J Med Chem 1984, 27, 1579.
【2】 Luther, R.R.; Plattner, J.J.; A-49816. Drugs Fut 1988, 13, 12, 1039.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	22671	4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride	100-07-2	C₈H₇ClO₂	详情	详情
(B)	23019	1,2-dichloro-3-ethoxybenzene; 2,3-dichlorophenyl ethyl ether		C₈H₈Cl₂O	详情	详情
(I)	23021	(2,3-dichloro-4-ethoxyphenyl)(4-methoxyphenyl)methanone		C₁₆H₁₄Cl₂O₃	详情	详情
(II)	23022	(2,3-dichloro-4-hydroxyphenyl)(4-methoxyphenyl)methanone		C₁₄H₁₀Cl₂O₃	详情	详情
(III)	23023	2-[2,3-dichloro-4-(4-hydroxybenzoyl)phenoxy]acetic acid		C₁₅H₁₀Cl₂O₅	详情	详情
(IV)	23024	2-[2,3-dichloro-4-(3-[[(2-chloroacetyl)amino]methyl]-4-hydroxybenzoyl)phenoxy]acetic acid		C₁₈H₁₄Cl₃NO₆	详情	详情
(C)	23020	2-chloro-N-(hydroxymethyl)acetamide	2832-19-1	C₃H₆ClNO₂	详情	详情

Extended Information