2-hydroxybenzonitrile -Drug Synthesis Database

【结构式】

【分子编号】21990

【品名】2-hydroxybenzonitrile

【CA登记号】611-20-1

【分子式】C₇H₅NO

【分子量】119.12284

【元素组成】C 70.58% H 4.23% N 11.76% O 13.43%

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)

By reaction of 3-(2-methyl-2-aminopropyl)indole (I) and 2-(2,3-epoxypropoxy)benzonitrile (II) by heating at 120-40 C followed by a treatment with HCl in ethanol. The starting products are obtained as follows: 1) The reaction of 3-(dimethylaminomethyl)indole (III) with 2-nitropropane (IV) by means of KOH gives 3-(2-methyl-2-nitropropyl)indole (V), which is then reduced with hydrazine and Raney-Ni in ethanol to yield (I). 2) The reaction of 2-hydroxybenzonitrile (VI) with epichlorohydrin (VII) by means of piperidine affords 2-(3-chloro-2-hydroxypropoxy)benzonitrile (VIII), which is epoxidized again to (II) by treatment with NaOH in hot THF-water.

参考文献中间体

合成目标

【1】 Kreighbaum, W.E.; et al.; Antihypertensive indole derivatives of phenoxypropanolamines with beta-adrenergic receptor antagonist and vasodilating activity. J Med Chem 1980, 23, 3, 285-289.
【2】 Weetman, D.F.; Castaner, J.; Bucindolol Hydrochloride. Drugs Fut 1981, 6, 7, 405.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情
(I)	37566	2-(1H-indol-3-yl)-1,1-dimethylethylamine; 1-(1H-indol-3-yl)-2-methyl-2-propanamine		C₁₂H₁₆N₂	详情	详情
(II)	37567	2-(2-oxiranylmethoxy)benzonitrile		C₁₀H₉NO₂	详情	详情
(III)	37568	N,N-Dimethyl-1H-indole-3-methanamine;Gramine;N-(1H-indol-3-ylmethyl)-N,N-dimethylamine; 3-(dimethylaminomethyl)-indole[;]1H-indol-3-yl-N,N-dimethylmethanamine	87-52-5	C₁₁H₁₄N₂	详情	详情
(IV)	21819	2-nitropropane	79-46-9	C₃H₇NO₂	详情	详情
(V)	37569	3-(2-methyl-2-nitropropyl)-1H-indole		C₁₂H₁₄N₂O₂	详情	详情
(VI)	21990	2-hydroxybenzonitrile	611-20-1	C₇H₅NO	详情	详情
(VII)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(VIII)	37570	2-(3-chloro-2-hydroxypropoxy)benzonitrile		C₁₀H₁₀ClNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

2-Cyanophenol (I) was condensed with 2-bromo-4'-methoxyacetophenone (II) in the presence of K2CO3 in acetone to give aminobenzofuran (III). This was acylated with trifluoroacetic anhydride, and the resulting trifluoroacetamide (IV) was alkylated with 2,5-dimethoxybenzyl chloride (V) under phase-transfer conditions to afford monobenzylated compound (VI). The benzofuro[3,2-b]pyridine nucleus was formed by acylation of the secondary amine group of (VI) with ethyl malonyl chloride (VII) to give (VIII) followed by an intramolecular Knoevenagel condensation over silica gel in refluxing CH2Cl2 to give (IX). Alkaline hydrolysis of the ester function of (IX) then provided the corresponding carboxylic acid.

参考文献中间体

合成目标

【1】 Mederski, W.K.R.; Wilm, C.; Schmitges, C.-J.; Oswald, M.; Dorsch, D.; Christadler, M.; Benzofuro[3,2-b]pyridines as mixed ETA/ETB and selective ETB endothelin receptor antagonists. Bioorg Med Chem Lett 1999, 9, 4, 619.

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)	21990	2-hydroxybenzonitrile	611-20-1	C₇H₅NO	详情	详情
(II)	21991	2-Methoxyphenacyl bromide; 2-bromo-1-(4-methoxyphenyl)-1-ethanone	2632-13-5	C₉H₉BrO₂	详情	详情
(III)	21992	(3-amino-1-benzofuran-2-yl)(4-methoxyphenyl)methanone		C₁₆H₁₃NO₃	详情	详情
(IV)	21993	2,2,2-trifluoro-N-[2-(4-methoxybenzoyl)-1-benzofuran-3-yl]acetamide		C₁₈H₁₂F₃NO₄	详情	详情
(V)	21994	2-(chloromethyl)-4-methoxyphenyl methyl ether; 2-(chloromethyl)-1,4-dimethoxybenzene	3840-27-5	C₉H₁₁ClO₂	详情	详情
(VI)	21995	[3-[(2,5-dimethoxybenzyl)amino]-1-benzofuran-2-yl](4-methoxyphenyl)methanone		C₂₅H₂₃NO₅	详情	详情
(VII)	13188	ethyl 3-chloro-3-oxopropanoate; 2-Ethoxycarbonylacetyl chloride; Ethyl malonyl chloride	36239-09-5	C₅H₇ClO₃	详情	详情
(VIII)	21997	ethyl 3-[(2,5-dimethoxybenzyl)[2-(4-methoxybenzoyl)-1-benzofuran-3-yl]amino]-3-oxopropanoate		C₃₀H₂₉NO₈	详情	详情
(IX)	21998	ethyl 1-(2,5-dimethoxybenzyl)-4-(4-methoxyphenyl)-2-oxo-1,2-dihydro[1]benzofuro[3,2-b]pyridine-3-carboxylate		C₃₀H₂₇NO₇	详情	详情

Extended Information