N-[[(2S)-1-ethylpyrrolidinyl]methyl]-2,3-dimethoxybenzamide -Drug Synthesis Database

【结构式】

【分子编号】42899

【品名】N-[[(2S)-1-ethylpyrrolidinyl]methyl]-2,3-dimethoxybenzamide

【CA登记号】

【分子式】C₁₆H₂₄N₂O₃

【分子量】292.37824

【元素组成】C 65.73% H 8.27% N 9.58% O 16.42%

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：(I)

This compound has been obtained by three related ways: 1. The lithiation of N-(1-ethylpyrrolidin-2(S)-ylmethyl)-2,3-dimethoxybenzamide (I) with n-BuLi gives the dilithium salt (II), which by reaction with tosyl azide yields 6-azido-N-(1-ethylpyrrolidin-2(S)-ylmethyl)-2,3-dimethoxybenzamide (III). The reduction of the azido group of (III) with SnCl2 yields the corresponding amino derivative (IV), which is finally brominated with Br2 to afford the target compound. 2. The reaction of N-(3,4-dimethoxyphenyl)carbamic acid tert-butyl ester (V) with n-BuLi and CO2 gives 6-(tert-butoxycarbonyl)-2,3-dimethoxybenzoic acid (VI), which is condensed with (S)-1-ethylpyrrolidin-2-ylmethylamine (VII) by means of SOCl2, yielding the already reported 2-aminobenzamide (IV). 3. The intermediate carboxylic acid (VI) can also be first brominated with Br2 to give 5-bromo-6-(tert-butoxycarbonyl)-2,3-dimethoxybenzoic acid (VIII), which is finally condensed with (S)-1-ethylpyrrolidin-2-ylmethylamine (VII) by means of SOCl2, yielding the target compound.

参考文献中间体

合成目标

【1】 Hogberg, M.; Novel substituted salicylamides and benzamides as selective dopamine D2-receptor antagonists. Drugs Fut 1991, 16, 4, 333.
【2】 Bengtsson, S.; Hogberg, T.; Secondary beta-aminobenzamide and heteroatom directed lithiation in the synthesis of 5,6-dimethoxyanthranilamides and related compounds. J Org Chem 1989, 54, 4549-4553.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	42899	N-[[(2S)-1-ethylpyrrolidinyl]methyl]-2,3-dimethoxybenzamide	C₁₆H₂₄N₂O₃	详情	详情
(II)	42900	lithium [2-[([[(2S)-1-ethylpyrrolidinyl]methyl]imino)(oxido)methyl]-3,4-dimethoxyphenyl]lithium	C₁₆H₂₂Li₂N₂O₃	详情	详情
(III)	42901	6-azido-N-[[(2S)-1-ethylpyrrolidinyl]methyl]-2,3-dimethoxybenzamide	C₁₆H₂₃N₅O₃	详情	详情
(IV)	42902	6-amino-N-[[(2S)-1-ethylpyrrolidinyl]methyl]-2,3-dimethoxybenzamide	C₁₆H₂₅N₃O₃	详情	详情
(V)	42903	tert-butyl 3,4-dimethoxyphenylcarbamate	C₁₃H₁₉NO₄	详情	详情
(VI)	42904	6-[(tert-butoxycarbonyl)amino]-2,3-dimethoxybenzoic acid	C₁₄H₁₉NO₆	详情	详情
(VII)	21345	(2S)-1-Ethyl-2-(aminomethyl)pyrrolidine; [(2S)-1-Ethylpyrrolidinyl]methanamine	C₇H₁₆N₂	详情	详情
(VIII)	42905	3-bromo-2-[(tert-butoxycarbonyl)amino]-5,6-dimethoxybenzoic acid	C₁₄H₁₈BrNO₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The lithiation of N-(1-ethylpyrroidin-2(S)-ylmethyl)-2,3-dimethoxybenzamide (I) with n-BuLi gives the dilithium salt (II), which by treatment with butyl borate, H2O2 and ammonium chloride yields N-(1-ethylpyrrolidin-2(S)-ylmethyl)-6-hydroxy-2,3-dimethoxybenzamide (III). Finally, this compound is iodinated with 123INa and chloramine T.

参考文献中间体

合成目标

【1】 Hogberg, M.; Novel substituted salicylamides and benzamides as selective dopamine D2-receptor antagonists. Drugs Fut 1991, 16, 4, 333.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	42899	N-[[(2S)-1-ethylpyrrolidinyl]methyl]-2,3-dimethoxybenzamide	C₁₆H₂₄N₂O₃	详情	详情
(II)	42900	lithium [2-[([[(2S)-1-ethylpyrrolidinyl]methyl]imino)(oxido)methyl]-3,4-dimethoxyphenyl]lithium	C₁₆H₂₂Li₂N₂O₃	详情	详情
(III)	42908	N-[[(2S)-1-ethylpyrrolidinyl]methyl]-6-hydroxy-2,3-dimethoxybenzamide	C₁₆H₂₄N₂O₄	详情	详情

Extended Information