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【结 构 式】

【分子编号】68820

【品名】(2R,3R,4S,5R)-2-(((Z)-3-amino-1-cyano-2-formamidoprop-1-en-1-yl)amino)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate

【CA登记号】

【 分 子 式 】C31H24N4O8

【 分 子 量 】580.554

【元素组成】C 64.13% H 4.17% N 9.65% O 22.05%

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:(XIX)

Condensation of 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl bromide (X) with diaminomaleonitrile (XI) yields the ribofuranosyl diamine (XII), which is alternatively prepared by N-protection of diamine (XI) with TMSCl in the presence of HMDS in refluxing acetonitrile and subsequent coupling of the obtained bis(silylamine) (XIII) with the D-ribofuranosyl acetate (XIV) by means of TMSOTf in CH2Cl2. Cyclization of diamine (XII) with HC(OEt)3 in the presence of NaOMe in anisole affords the 4,5-dicyanoimidazole derivative (XV), which undergoes regioselective addition of NaOMe in MeOH to give imidate (XVI). Finally, Hofmann rearrangement of imidate (XVI) with NaOCl in the presence of NaOH yields imidazolecarbonitrile (V) .
Alternatively, formylation of diaminomaleonitrile (XI) with HCOOH in benzene leads to N-formyldiaminomaleonitrile (XVII) , which is then silylated with TMSCl in the presence of HMDS to yield the protected amine (XVIII). Finally, amine (XVIII) is condensed with the ribofuranosyl acetate (XIV) in the presence of TMSOTf in CH2Cl2 to give compound (XIX), which undergoes cyclization using AcOH in refluxing benzene yielding nitrile (XV) .

1 Ferris, J.P., Devadas, B., Huang, C.H., Ren, W.Y. Novel synthesis of 5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide and 5-amino-1-(beta-D-ribopyranosyl)imidazole-4-carboxamide. J Org Chem 1985, 50(6): 747-54.
2 Ohtsuka, Y. Chemistry of diaminomaleonitrile. 1. Selective preparations of monoformyldiaminomaleonitrile and imidazoles by reaction with formicacid. J Org Chem 1976, 41(4): 713-4.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 37430 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carbonitrile C9H12N4O4 详情 详情
(X) 33832 [(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate C26H21BrO7 详情 详情
(XI) 16903 (Z)-2,3-diamino-2-butenedinitrile;diaminomaleonitrile 1187-42-4 C4H4N4 详情 详情
(XII) 68818 (2R,3R,4S,5R)-2-((benzoyloxy)methyl)-5-(((Z)-1,3-diamino-1-cyanoprop-1-en-2-yl)amino)tetrahydrofuran-3,4-diyl dibenzoate C30H24N4O7 详情 详情
(XIII) 68815 (Z)-4-amino-2,3-bis((trimethylsilyl)amino)but-2-enenitrile C10H20N4Si2 详情 详情
(XIV) 26984 (2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate C28H24O9 详情 详情
(XV) 68819 (2R,3R,4S,5R)-2-(5-(aminomethyl)-4-cyano-1H-imidazol-1-yl)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate C31H22N4O7 详情 详情
(XVI) 68821 methyl 4-cyano-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1H-imidazole-5-carbimidate C11H14N4O5 详情 详情
(XVII) 68816 N-formyldiaminomaleonitrile;(Z)-N-(1,3-diamino-1-cyanoprop-1-en-2-yl)formamide C5H4N4O 详情 详情
(XVIII) 68817 (Z)-N-(3-amino-1-cyano-2-((trimethylsilyl)amino)prop-1-en-1-yl)formamide C8H12N4OSi 详情 详情
(XIX) 68820 (2R,3R,4S,5R)-2-(((Z)-3-amino-1-cyano-2-formamidoprop-1-en-1-yl)amino)-5-((benzoyloxy)methyl)tetrahydrofuran-3,4-diyl dibenzoate C31H24N4O8 详情 详情
Extended Information