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【结 构 式】 
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【分子编号】59036 【品名】2-{[5-{[2-(acetyloxy)ethyl]amino}-2-({4-[({2-{[(E)-(dimethylamino)methylidene]amino}-4-[(4-nitrophenethyl)oxy]-6-pteridinyl}methyl)amino]benzoyl}amino)-5-oxopentanoyl]amino}ethyl acetate 【CA登记号】 |
【 分 子 式 】C38H45N11O10 【 分 子 量 】815.84344 【元素组成】C 55.94% H 5.56% N 18.89% O 19.61% |
合成路线1
该中间体在本合成路线中的序号：(VII)Esterification of ethanolamine hydrochloride (I) by means of acetyl chloride in HOAc yields 2-aminoethyl acetate (II). The carboxyl groups of folic acid (III) are protected by coupling with amino ester (II) in the presence of EDC, to produce diamide (IV). Subsequent condensation of (IV)with dimethylformamide diethylacetal (DMF-DEA) gives formamidine (V). The 4-carbonyl group of (V) is then protected as the phenethyl ether (VII) by treatment with 4-nitrophenethyl alcohol (VI) under Mitsunobu coupling conditions.
| 【1】 Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 . |
| 【2】 Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 . |
| 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) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (II) | 59032 | 2-aminoethyl acetate | C4H9NO2 | 详情 | 详情 | |
| (III) | 59033 | N-(4-{[(2-amino-4-oxo-3,4-dihydro-6-pteridinyl)methyl]amino}benzoyl)glutamic acid | C19H19N7O6 | 详情 | 详情 | |
| (IV) | 59034 | 2-({5-{[2-(acetyloxy)ethyl]amino}-2-[(4-{[(2-amino-4-oxo-3,4-dihydro-6-pteridinyl)methyl]amino}benzoyl)amino]-5-oxopentanoyl}amino)ethyl acetate | C27H33N9O8 | 详情 | 详情 | |
| (V) | 59035 | 2-({5-{[2-(acetyloxy)ethyl]amino}-2-[(4-{[(2-{[(E)-(dimethylamino)methylidene]amino}-4-oxo-3,4-dihydro-6-pteridinyl)methyl]amino}benzoyl)amino]-5-oxopentanoyl}amino)ethyl acetate | C30H38N10O8 | 详情 | 详情 | |
| (VI) | 32472 | 2-(4-nitrophenyl)-1-ethanol | 100-27-6 | C8H9NO3 | 详情 | 详情 |
| (VII) | 59036 | 2-{[5-{[2-(acetyloxy)ethyl]amino}-2-({4-[({2-{[(E)-(dimethylamino)methylidene]amino}-4-[(4-nitrophenethyl)oxy]-6-pteridinyl}methyl)amino]benzoyl}amino)-5-oxopentanoyl]amino}ethyl acetate | C38H45N11O10 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Partial hydrolysis of diacetate (VII) by means of ethanolamine, followed by reprotection with DMF-DEA, affords the desired mono-hydrolyzed compound (VIII), along with other by-products that are separated by column chromatography. Phosphitylation of alcohol (VIII) with cyanoethyl N,N-diisopropylphosphonamidic chloride furnishes the activated phosphoramidite (IX).
| 【1】 Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 . |
| 【2】 Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 59036 | 2-{[5-{[2-(acetyloxy)ethyl]amino}-2-({4-[({2-{[(E)-(dimethylamino)methylidene]amino}-4-[(4-nitrophenethyl)oxy]-6-pteridinyl}methyl)amino]benzoyl}amino)-5-oxopentanoyl]amino}ethyl acetate | C38H45N11O10 | 详情 | 详情 | |
| (VIII) | 59037 | 2-({2-({4-[({2-{[(E)-(dimethylamino)methylidene]amino}-4-[(4-nitrophenethyl)oxy]-6-pteridinyl}methyl)amino]benzoyl}amino)-5-[(2-hydroxyethyl)amino]-5-oxopentanoyl}amino)ethyl acetate | C36H43N11O9 | 详情 | 详情 | |
| (IX) | 59038 | 16-cyano-13-(diisopropylamino)-5-({4-[({2-{[(E)-(dimethylamino)methylidene]amino}-4-[(4-nitrophenethyl)oxy]-6-pteridinyl}methyl)amino]benzoyl}amino)-4,8-dioxo-12,14-dioxa-3,9-diaza-13-phosphahexadec-1-yl acetate | C45H60N13O10P | 详情 | 详情 |