文献类型：专利

英文题名：Preparing 2,3,4-trisubstituted pyrrole ring derivatives comprises e.g. reacting 2-acetyloxy-methylene-2,3-allene acid benzyl ester with substituted tosylated amine compound, and then subjecting to column chromatography

作者：CHEN C;DONG W;HU J;LIN C;TONG X

机构：[1]UNIV EAST CHINA SCI & TECHNOLOGY

申请号：CN104710339-A

申请日：2015-01-22

公开日：2015-06-17

语种：英文

收录：DERWENT

摘要：NOVELTY - Preparing 2,3,4-trisubstituted pyrrole ring derivatives comprises e.g. (i) reacting substituted 2-bromoacetaldehyde (II) with N-tosylpivalamide to obtain substituted tert-butyl 2-oxoethyl(tosyl)carbamate (III), (ii) adding 2-(4-methylphenylsulfonamido)acetic acid (VI) and pivaloyl chloride to obtain Weinreb amide (VII), (iii) carrying out Baylis-Hillman reaction to obtain substituted hydroxy group linked alpha -acid benzyl ester (X), reacting (X) with acetyl chloride to obtain 2-acetyloxy-methylene-2,3-allene acid benzyl ester (XI), and (iv) reacting (XI) with substituted tosylated amine (V). USE - The method is useful for preparing 2,3,4-trisubstituted pyrrole ring derivative (claimed). ADVANTAGE - The method provides a novel and convenient synthetic method of poly-substituted pyrrole ring derivatives. DETAILED DESCRIPTION - Preparing 2,3,4-trisubstituted pyrrole ring derivatives comprises (i) reacting substituted 2-bromoacetaldehyde compound of formula (II) with N-tosylpivalamide (TsNHBoc) in acetone solvent in presence of potassium carbonate base at room temperature to obtain substituted tert-butyl 2-oxoethyl(tosyl)carbamate compound of formula (III), then reacting (III) under the action of trifluoroacetic acid using dichloromethane as solvent, removing tert-butoxycarbonyl group to obtain substituted tosylated amine compound of formula (IV), (ii) adding 2-(4-methylphenylsulfonamido)acetic acid (VI) as precursor, triethylamine and pivaloyl chloride in dichloromethane solvent, then adding N,O-dimethyl-hydroxylamine hydrochloride and triethylamine to obtain Weinreb amide (VII), then reacting (VII) with methyl magnesium bromide Grignard reagent and tetrahydrofuran solvent at 0 degrees C to obtain 4-methyl-N-(2-oxopropyl)benzenesulfonamide (VIII), (iii) carrying out Baylis-Hillman reaction of united acid benzyl ester (IX) in 1,4-diazabicyclo(2.2.2)octane (triethylenediamine) catalyst and tetrahydrofuran as a solvent with paraformaldehyde to obtain substituted hydroxy group linked alpha -acid benzyl ester (X), reacting (X) with acetyl chloride in dichloromethane solvent in presence of triethylamine at room temperature to obtain 2-acetyl-oxy-methylene-2,3-allene acid benzyl ester (XI), and (iv) reacting (XI) with substituted tosylated amine compound of formula (V) in 20 mol% 1,4-diazabicyclo(2.2.2)octane catalyst and an inorganic base potassium carbonate and in 1,4-dioxane as solvent at 80 degrees C for 12-36 hours, rotary evaporating to remove the solvent, and then subjecting to column chromatography to obtain final product. R = phenyl (Ph), 4-F-Ph, 4-Cl-Ph, 4-Br-Ph, 3-NO2-Ph, 4-CF3-Ph, 4-methyl-Ph, 4-MeO-Ph, 2,4-Me2-Ph, 2-furyl, 2-thienyl, methyl or cyclopropyl; and n = 1-100.