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【结 构 式】

【分子编号】11014

【品名】diethyl (2S)-2-[(4-[1-[(2,4-diamino-6-pteridinyl)methyl]propyl]benzoyl)amino]pentanedioate

【CA登记号】

【 分 子 式 】C26H33N7O5

【 分 子 量 】523.5922

【元素组成】C 59.64% H 6.35% N 18.73% O 15.28%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(X)

A new synthesis for edatrexate has been described: The reaction of 2,4-diamino-6-(bromomethyl)pteridine (I) with tributylphosphine (II) in DMSO gives the corresponding phosphonium salt (III), which is condensed wtih 4-propionylbenzoic acid methyl ester (IV) by means of NaH in DMSO, affording 4-[1-(2,4-diaminopteridin-6-yl)-1-ethylvinyl]benzoic acid methyl ester (V). The hydrogenation of (V) with H2 and PtO2 in acetic acid gives 4-[1-(2,4-diamino-6,7-dihydropteridin-6-ylmethyl)propyl]benzoic acid methyl ester (VI), which, without isolation, is dehydrogenated with H2O2 in the same solvent yielding 4-[1-(2,4-diaminopteridin-6-ylmethyl)propyl]benzoic acid methyl ester (VII). The hydrolysis of (VII) with NaOH in DMSO - water affords the corresponding free acid (VIII), which is condensed with L-glutamic acid diethyl ester (IX) by means of isobutoxycarbonylchloride and triethylamine in DMF, giving edatrexate diethyl ester (X). Finally, this compound is hydrolyzed with NaOH in methanol.

1 Johnson, C.A.; Sirotnak, F.M.; Piper, J.R.; Otter, G.M.; Synthesis and antifolate evaluation of 10-ethyl-5-methyl-5,10-dideazaaminopterin and an alternative synthesis of 10-ethyl-10-deazaaminopterin (edatrexate). J Med Chem 1992, 35, 16, 3002.
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) 11006 2-Amino-6-(bromomethyl)-4-pteridinylamine; 6-(Bromomethyl)-2,4-pteridinediamine 52853-40-4 C7H7BrN6 详情 详情
(III) 11007 Tributyl[(2,4-diamino-6-pteridinyl)methyl]phosphonium bromide C19H34BrN6P 详情 详情
(IV) 11008 methyl 4-propionylbenzoate C11H12O3 详情 详情
(V) 11009 methyl 4-[(E)-2-(2,4-diamino-6-pteridinyl)-1-ethylethenyl]benzoate C18H18N6O2 详情 详情
(VI) 11010 methyl 4-[1-[(2,4-diamino-5,6,7,8-tetrahydro-6-pteridinyl)methyl]propyl]benzoate C18H24N6O2 详情 详情
(VII) 11011 methyl 4-[1-[(2,4-diamino-6-pteridinyl)methyl]propyl]benzoate C18H20N6O2 详情 详情
(VIII) 11012 4-[1-[(2,4-Diamino-6-pteridinyl)methyl]propyl]benzoic acid C17H18N6O2 详情 详情
(IX) 11013 diethyl (2S)-2-aminopentanedioate C9H17NO4 详情 详情
(X) 11014 diethyl (2S)-2-[(4-[1-[(2,4-diamino-6-pteridinyl)methyl]propyl]benzoyl)amino]pentanedioate C26H33N7O5 详情 详情
Extended Information