dimethyl 2-aminosuccinate -Drug Synthesis Database

【结构式】

【分子编号】39047

【品名】dimethyl 2-aminosuccinate

【CA登记号】

【分子式】C₆H₁₁NO₄

【分子量】161.15768

【元素组成】C 44.72% H 6.88% N 8.69% O 39.71%

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：(II)

Condensation of dimethyl aspartate (II) with benzyloxy carbonyl sarcosine (I) using DCI gave dimethyl benzyloxycarbonyl sarcosylaspartate (III). Removal of benzyloxycarbonyl function from (III) by catalytic hydrogenation or HBr-AcOH followed by cyclization, effected by storage over P2O5 in vacuo for 48 h, gave methyl (1-methyl-2,5-dioxopiperazin-3-yl)acetate (IV). When (IV) was reacted with ethylamine in a sealed tube for 36 h, it yielded N-ethyl-2-(1-methyl-2,5,dioxopiperazin-3-yl)acetamide (V). The compound (V) was reduced with LiAlH4 to give 1-methyl-3-(2-ethylamino)ethylpiperazine (VI). When (VI) was condensed with ethyl chloroformate (A) at pH 3-3.5, a mixture of monocarbamates (VIIa, VIIb) were obtained. Cyclization of the monocarbamates (VIIa, VIIb) were effected by treatment with sodium ethoxide to afford 3-ethyl-8-methyl-1,3,8-triazabicyclo[4.4.0]decan-2-one (centperazine). When (VI) was reacted with ethyl chloroformate (A) in the presence of NaOC2H5 or Et3N, the dicarbamate (VIII) was formed.

参考文献中间体

合成目标

【1】 Saxena, R.; et al.; Studies in potential filaricides. 5. 3-Ethyl-8-methyl-1,3,8-triazabicyclo[4.4.0]decan-2-one, a new antifilarial agent. J Med Chem 1971, 14, 10, 929.
【2】 Arya, V.P.; Centperazine. Drugs Fut 1980, 5, 5, 229.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(A)	12229	(2R,3S)-5,5-Dimethoxy-3-(phenylselanyl)-1,2-pentanediol	C₁₃H₂₀O₄Se	详情	详情
(VIIa)	39052	ethyl ethyl[2-(4-methyl-2-piperazinyl)ethyl]carbamate	C₁₂H₂₅N₃O₂	详情	详情
(VIIb)	39053	ethyl 2-[2-(ethylamino)ethyl]-4-methyl-1-piperazinecarboxylate	C₁₂H₂₅N₃O₂	详情	详情
(I)	39046	(benzyloxy)carbonyl(methyl)carbamic acid	C₁₀H₁₁NO₄	详情	详情
(II)	39047	dimethyl 2-aminosuccinate	C₆H₁₁NO₄	详情	详情
(III)	39048	dimethyl 2-([2-[[(benzyloxy)carbonyl](methyl)amino]acetyl]amino)succinate	C₁₇H₂₂N₂O₇	详情	详情
(IV)	39049	methyl 2-(4-methyl-3,6-dioxo-2-piperazinyl)acetate	C₈H₁₂N₂O₄	详情	详情
(V)	39050	N-ethyl-2-(4-methyl-3,6-dioxo-2-piperazinyl)acetamide	C₉H₁₅N₃O₃	详情	详情
(VI)	39051	N-ethyl-2-(4-methyl-2-piperazinyl)-1-ethanamine; N-ethyl-N-[2-(4-methyl-2-piperazinyl)ethyl]amine	C₉H₂₁N₃	详情	详情
(VIII)	39054	ethyl 2-[2-[(ethoxycarbonyl)(ethyl)amino]ethyl]-4-methyl-1-piperazinecarboxylate	C₁₅H₂₉N₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Coupling between N-Boc-aspartic acid (I) and dimethyl aspartate (II) using EDC and DMAP affords tripeptide (III). Subsequent Boc group deprotection in (III) employing trifluoroacetic acid leads to amine (IV).This is then coupled to the polyethyleneglycol-acid (V) producing amide (VI). Basic hydrolysis of the ester groups of (VI) then gives the tetra-carboxylic acid scaffold (VII).

参考文献中间体

合成目标

【1】 Choe, Y.H.; et al.; Anticancer drug delivery systems: multi-loaded N-4-acyl poly(ethylene glycol) prodrugs of ara-C. II. Efficacy in ascites and solid tumors. J Control Release 2002, 79, 1-3, 55.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	57571	N-(tert-butoxycarbonyl)aspartic acid	C₉H₁₅NO₆	详情	详情
(II)	39047	dimethyl 2-aminosuccinate	C₆H₁₁NO₄	详情	详情
(III)	57572	dimethyl 2-[(2-[(tert-butoxycarbonyl)amino]-4-{[3-methoxy-1-(methoxycarbonyl)-3-oxopropyl]amino}-4-oxobutanoyl)amino]succinate	C₂₁H₃₃N₃O₁₂	详情	详情
(IV)	57573	dimethyl 2-[(2-amino-4-{[3-methoxy-1-(methoxycarbonyl)-3-oxopropyl]amino}-4-oxobutanoyl)amino]succinate	C₁₆H₂₅N₃O₁₀	详情	详情
(V)	65175		C₄H₇O₃	详情	详情
(VI)	65176		C₂₀H₃₀N₃O₁₂	详情	详情
(VII)	65177		C₁₆H₂₂N₃O₁₂	详情	详情

Extended Information