ethyl 2-({2-[(2,2-dimethoxyethyl)amino]-2-oxoacetyl}amino)acetate -Drug Synthesis Database

【结构式】

【分子编号】63557

【品名】ethyl 2-({2-[(2,2-dimethoxyethyl)amino]-2-oxoacetyl}amino)acetate

【CA登记号】

【分子式】C₁₀H₁₈N₂O₆

【分子量】262.2628

【元素组成】C 45.8% H 6.92% N 10.68% O 36.6%

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：(XIV)

Acylation of glycine ethyl ester (X) with ethyl oxalyl chloride (XI) provides the oxalic acid mono-amide (XII). Subsequent condensation of (XII) with aminoacetaldehyde dimethylacetal (XIII) affords the diamide (XIV). Cyclization of (XIV) under acetal hydrolysis conditions leads to pyrazinone (XV). This is then brominated to (XVI) employing POBr3 in refluxing dichloroethane. Condensation of the bromopyrazinone (XVI) with amine (IX) at 120 C in a sealed vessel furnishes the aminopyrazinone (XVII). After chlorination of (XVII) with N-chlorosuccinimide, the resultant chloropyrazine ester (XVIII) is hydrolyzed to acid (XIX) under alkaline conditions

参考文献中间体

合成目标

【1】 Selnick, H.G.; Rittle, K.E.; Barrow, J.C.; Morrissette, M.M.; Nantermet, P.G.; Staas, D. (Merck & Co., Inc.); Thrombin inhibitors. WO 0257225 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	63218	2-(2-amino-1,1-difluoroethyl)-1-pyridiniumolate		C₇H₈F₂N₂O	详情	详情
(X)	10309	ethyl 2-aminoacetate; Glycine ethyl ester	459-73-4	C₄H₉NO₂	详情	详情
(XI)	11043	Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride	4755-77-5	C₄H₅ClO₃	详情	详情
(XII)	63556	ethyl 2-[(2-ethoxy-2-oxoethyl)amino]-2-oxoacetate		C₈H₁₃NO₅	详情	详情
(XIII)	34158	aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine	22483-09-6	C₄H₁₁NO₂	详情	详情
(XIV)	63557	ethyl 2-({2-[(2,2-dimethoxyethyl)amino]-2-oxoacetyl}amino)acetate		C₁₀H₁₈N₂O₆	详情	详情
(XV)	63558	ethyl 2-[2,3-dioxo-3,4-dihydro-1(2H)-pyrazinyl]acetate		C₈H₁₀N₂O₄	详情	详情
(XVI)	63219	ethyl 2-[3-bromo-2-oxo-1(2H)-pyrazinyl]acetate		C₈H₉BrN₂O₃	详情	详情
(XVII)	63220	2-(2-{[4-(2-ethoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2-pyrazinyl]amino}-1,1-difluoroethyl)-1-pyridiniumolate		C₁₅H₁₆F₂N₄O₄	详情	详情
(XVIII)	63221	2-(2-{[5-chloro-4-(2-ethoxy-2-oxoethyl)-3-oxo-3,4-dihydro-2-pyrazinyl]amino}-1,1-difluoroethyl)-1-pyridiniumolate		C₁₅H₁₅ClF₂N₄O₄	详情	详情
(XIX)	63222	2-(2-{[4-(carboxymethyl)-5-chloro-3-oxo-3,4-dihydro-2-pyrazinyl]amino}-1,1-difluoroethyl)-1-pyridiniumolate		C₁₃H₁₁ClF₂N₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Acylation of glycine ethyl ester (I) with ethyl oxalyl chloride (II) affords amide (III). Subsequent reaction of (III) with aminoacetaldehyde dimethyl acetal (IV) produces the oxalic acid diamide (V). Cyclization of (V) under acidic conditions furnishes the pyrazine dione (VI), which is further brominated to (VII) employing phosphorus oxybromide.

参考文献中间体

合成目标

【1】 Selnick, H.G.; Newton, R.C.; Newton, C.L.; Barrow, J.C.; Nantermet, P.G. (Merck & Co., Inc.); Thrombin inhibitors. WO 0311222 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	10309	ethyl 2-aminoacetate; Glycine ethyl ester	459-73-4	C₄H₉NO₂	详情	详情
(II)	11043	Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride	4755-77-5	C₄H₅ClO₃	详情	详情
(III)	63556	ethyl 2-[(2-ethoxy-2-oxoethyl)amino]-2-oxoacetate		C₈H₁₃NO₅	详情	详情
(IV)	34158	aminoacetaldehyde dimethylacetal; 2,2-dimethoxy-1-ethanamine; 2,2-dimethoxyethylamine	22483-09-6	C₄H₁₁NO₂	详情	详情
(V)	63557	ethyl 2-({2-[(2,2-dimethoxyethyl)amino]-2-oxoacetyl}amino)acetate		C₁₀H₁₈N₂O₆	详情	详情
(VI)	63558	ethyl 2-[2,3-dioxo-3,4-dihydro-1(2H)-pyrazinyl]acetate		C₈H₁₀N₂O₄	详情	详情
(VII)	63219	ethyl 2-[3-bromo-2-oxo-1(2H)-pyrazinyl]acetate		C₈H₉BrN₂O₃	详情	详情

Extended Information