Ioxipride, NCQ-298

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.

参考文献标题:Novel substituted salicylamides and benzamides as selective dopamine D2-receptor antagonists
文献作者:H鰃berg,M.
参考来源:Drugs Fut 1991,16(4),333


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.

参考文献标题:Efficient stereoconservative syntheses of 1-substituted (S)- and (R)-2-aminomethylpyrrolidines
文献作者:R鋗sby,S.; H鰃berg,T.; Str鰉,P.
参考来源:Acta Chem Scand 1989,43660-664


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.
参考文献标题:Cyanide as an efficient and mild catalyst in the aminolysis of esters
文献作者:H鰃berg,T.; R鋗sby,S.; Str鰉,P.; Ebner,M.
参考来源:J Org Chem 1987,522033-2036