NCQ-318

Chemical Name: (S)-(-)-2-Amino-3-bromo-N-[(1-ethyl-2-pyrrolidin- yl)methyl]-5,6-dimethoxybenzamide
CAS No. 101460-34-8
项目整合开发状态: Biological Testing
项目研究机构: AstraZeneca (Originator)
合成路线: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.

合成路线:The alkylation of L-proline (I) with ethyl iodide (II) and K2CO3 gives N-ethylproline ethyl ester (III),which is treated with ammonia in methanol to afford N-ethyl-L-prolinamide (IV).The reduction of (IV) with LiAlH4 yields (S)-1-ethylpyrrolidin-2-ylmethylamine (V),which is condensed with 3-bromo-2,5,6-trimethoxybenzoyl chloride (VI) to provide the corresponding amide (VII).Finally,this compound is partially demethylated with BBr3 to provide the target compound.

合成路线:The alkylation of L-proline (I) with ethyl iodide (II) and K2CO3 gives N-ethylproline ethyl ester (III),which is treated with ammonia in methanol to afford N-ethyl-L-prolinamide (IV).The reduction of (IV) with LiAlH4 yields (S)-1-ethylpyrrolidin-2-ylmethylamine (V),which is condensed with 3-iodo-2,5,6-trimethoxybenzoyl chloride (VI) to provide the corresponding amide (VII).Finally,this compound is partially demethylated with BBr3 to provide the target compound.

合成路线: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.