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【结 构 式】

【分子编号】21994

【品名】2-(chloromethyl)-4-methoxyphenyl methyl ether; 2-(chloromethyl)-1,4-dimethoxybenzene

【CA登记号】3840-27-5

【 分 子 式 】C9H11ClO2

【 分 子 量 】186.63784

【元素组成】C 57.92% H 5.94% Cl 19% O 17.14%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(V)

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.

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

合成路线2

该中间体在本合成路线中的序号:(III)

5-Fluoro-2-phenoxyaniline (I) was acylated with acetyl chloride and triethylamine to afford acetamide (II). Alkylation of the amide N by 2,5-dimethoxybenzyl chloride (III) in the presence of NaH provided the target tertiary amide.

1 Yamamoto, Y.; Yoshida, M.; Nakamura, T.; Tomisawa, K.; Harada, K.; Nagamine, M.; Nakazato, A.; Chaki, S.; Okubo, T. (Nihon Nohyaku Co., Ltd.; Taisho Pharmaceutical Co., Ltd.); Aryloxyaniline derivs.. EP 1004573; JP 1999171844; US 2002147191; US 6333358; US 6476056; WO 9906353 .
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) 56384 5-fluoro-2-phenoxyphenylamine; 5-fluoro-2-phenoxyaniline C12H10FNO 详情 详情
(II) 56385 N-(5-fluoro-2-phenoxyphenyl)acetamide C14H12FNO2 详情 详情
(III) 21994 2-(chloromethyl)-4-methoxyphenyl methyl ether; 2-(chloromethyl)-1,4-dimethoxybenzene 3840-27-5 C9H11ClO2 详情 详情
Extended Information