• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】31951

【品名】1H-imidazole-4,5-dicarboxylic acid

【CA登记号】570-22-9

【 分 子 式 】C5H4N2O4

【 分 子 量 】156.09784

【元素组成】C 38.47% H 2.58% N 17.95% O 41%

与该中间体有关的原料药合成路线共 4 条

合成路线1

该中间体在本合成路线中的序号:(II)

The hydrolysis of diethyl imidazole-4,5-dicarboxylate (I) with aqueous NaOH gives imidazole-4,5-dicarboxylic acid (II), which is partially decarboxylated by treatment with refluxing aniline yielding 4-anilinocarbonylimidazole (III). The hydrolysis of (III) with refluxing aqueous HCl affords imidazole-4-carboxylic acid (IV), which is finally esterified with ethanol and dry HCl at reflux temperature.

1 Schen, T.-T.; et al.; US 3438992 .
2 Serradell, M.N.; Blancafort, P.; Hillier, K.; Castaner, J.; C-751. Drugs Fut 1981, 6, 4, 218.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 12294 Aniline; Phenylamine 62-53-3 C6H7N 详情 详情
(I) 37424 diethyl 1H-imidazole-4,5-dicarboxylate C9H12N2O4 详情 详情
(II) 31951 1H-imidazole-4,5-dicarboxylic acid 570-22-9 C5H4N2O4 详情 详情
(III) 37425 N-phenyl-1H-imidazole-4-carboxamide C10H9N3O 详情 详情
(IV) 37426 1H-imidazole-4-carboxylic acid C4H4N2O2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(I)

The reaction of imidazole-4,5-dicarboxylic acid (I) with SOCl2 in refluxing benzene gives the corresponding acid chloride (II), which is condensed with 7-beta-[D-(-)-alpha-aminophenylacetamido]cephalosporanic acid sodium salt (III) by means of triethylamine in dichloromethane to afford 7-beta-[D-(-)-alpha-[4(5)-carboxyimidazole-5(4)-carboxamido]phenyl acetamidolcephalosporanic acid (IV). Finally, this compound is condensed with 4-pyridineethanesulfonic acid (V) by means of NaI in water at 70 C.

1 Yasuda, N.; Eguchi, C.; Okutsu, M.; Hirose, Y. (Ajinomoto Co., Inc.); Imidazoledicarboxylic acid substituted cephalosporin derivatives. DE 2826546; FR 2394550; JP 54005974; US 4217450 .
2 Castaner, J.; Serradell, M.N.; Blancafort, P.; AC-1370. Drugs Fut 1982, 7, 6, 373.
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) 31951 1H-imidazole-4,5-dicarboxylic acid 570-22-9 C5H4N2O4 详情 详情
(II) 31952 1H-imidazole-4,5-dicarbonyl dichloride C5H2Cl2N2O2 详情 详情
(III) 31953 Sodium (6R,7R)-3-[(acetoxy)methyl]-7-[[(2R)-2-amino-2-phenylethanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; 7- beta-[D-(-)-alpha-Aminophenylacetamido]cephalosporanic acid sodium salt C18H18N3NaO6S 详情 详情
(IV) 31954 7-beta-[D-(-)-alpha-[4(5)-Carboxyimidazole-5(4)-carboxamido]phenyl acetamidolcephalosporanic acid; Disodium (6R,7R)-3-[(acetoxy)methyl]-7-[((2R)-2-[[(4-carboxylato-1H-imidazol-5-yl)carbonyl]amino]-2-phenylethanoyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate C23H19N5Na2O9S 详情 详情
(V) 31955 4-Pyridineethanesulfonic acid; 2-(4-Pyridinyl)-1-ethanesulfonic acid 53054-76-5 C7H9NO3S 详情 详情

合成路线3

该中间体在本合成路线中的序号:(I)

The esterification of 1H-imidazole-4,5-dicarboxylic acid (I) with EtOH and sulfuric acid gives the diethyl ester (II), which is brominated with NBS in acetonitrile, yielding the 2-bromo derivative (III). The hydrolysis of (III) by means of hot aqueous Na2CO3 affords the 2-bromo-1H-imidazole-4,5-dicarboxylic acid (IV), which is diazocoupled with the labeled diazonium ion (V) to provide the monolabeled azo acid (VI). The reaction of acid (VI) with 15NH4Cl and DEC in acetonitrile gives the doubly labeled azoamide (VII), which is reduced with H2 over Pd/C in methanol to yield the doubly labeled 5-amino-1H-imidazole-4-carboxamide (VIII). The cyclization of (VIII) with sodium 13C-ethylxanthate (IX) in DMF affords the mercaptoxanthine (X), which is reduced to the hypoxanthine (XI) with Raney Ni and formic acid. The reaction of (XI) with POCl3 in hot N,N-dimethylaniline provides the triply labeled chloropurine (XII), which is submitted to enzymatic trans-glycosylation with 7-methylguanosine or thymidine and purine nucleoside phosphorylase (PNP) and thymidine phosphorylase (TP) to give the glycosylated chloropurine (XIII). Finally, this compound is treated with 15NH4Cl and KHCO3 in hot anhydrous DMSO to afford the target tetralabeled adenine nucleoside.

1 Abad, J.-L.; Gaffney B.L.; Jones R.A.; 15N-multilabeled adenine and guanine nucleosides syntheses of [1,3,NH2-15N3]- and [2-13C-1,3NH2-15N3]-labeled adenosine, guanosine , 2'-deoxyadenosine, and 2'-deoxyguanosine. J Org Chem 1999, 64, 18, 6575.
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) 31951 1H-imidazole-4,5-dicarboxylic acid 570-22-9 C5H4N2O4 详情 详情
(II) 27424 3-(1-trityl-1H-imidazol-4-yl)-1-propanol C25H24N2O 详情 详情
(III) 51896 diethyl 2-bromo-1H-imidazole-4,5-dicarboxylate C9H11BrN2O4 详情 详情
(IV) 51897 2-bromo-1H-imidazole-4,5-dicarboxylic acid C5H3BrN2O4 详情 详情
(V) 51898 4-bromobenzenediazonium C6H4BrN2 详情 详情
(V) 51907 4-bromobenzenediazonium C6H4BrN2 详情 详情
(VI) 51899 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxylic acid C10H7BrN4O2 详情 详情
(VI) 51908 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxylic acid C10H7BrN4O2 详情 详情
(VII) 51900 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxamide C10H8BrN5O 详情 详情
(VII) 51909 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxamide C10H8BrN5O 详情 详情
(VIII) 11015 5-Amino-1H-imidazole-4-carboxamide 360-97-4 C4H6N4O 详情 详情
(VIII) 51901 5-amino-1H-imidazole-4-carboxamide C4H6N4O 详情 详情
(IX) 51902   C3H5NaOS2 详情 详情
(IX) 51910   C3H5NaOS2 详情 详情
(X) 51903   C5H3N4NaOS 详情 详情
(X) 51911   C5H3N4NaOS 详情 详情
(XI) 51904 1,9-dihydro-6H-purin-6-one C5H4N4O 详情 详情
(XI) 51912 1,9-dihydro-6H-purin-6-one C5H4N4O 详情 详情
(XII) 17692 6-Chloropurine; 6-chloro-9H-purine 87-42-3 C5H3ClN4 详情 详情
(XII) 51905 6-chloro-9H-purine C5H3ClN4 详情 详情
(XIII) 18716 6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol 2004-06-0 C10H11ClN4O4 详情 详情
(XIII) 51906 (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol C10H11ClN4O4 详情 详情

合成路线4

该中间体在本合成路线中的序号:(I)

The esterification of 1H-imidazole-4,5-dicarboxylic acid (I) with EtOH and sulfuric acid gives the diethyl ester (II), which is brominated with NBS in acetonitrile, yielding the 2-bromo derivative (III). The hydrolysis of (III) by means of hot aqueous Na2CO3 affords the 2-bromo-1H-imidazole-4,5-dicarboxylic acid (IV), which is diazocoupled with the labeled diazonium ion (V) to provide the monolabeled azo acid (VI). The reaction of acid (VI) with 15NH4Cl and DEC in acetonitrile gives the doubly labeled azoamide (VII), which is reduced with H2 over Pd/C in methanol to yield the doubly labeled 5-amino-1H-imidazole-4-carboxamide (VIII). The cyclization of (VIII) with sodium ethylxanthate (IX) in DMF affords the mercaptoxanthine (X), which is reduced to the hypoxanthine (XI) with Raney Ni and formic acid. The reaction of (XI) with POCl3 in hot N,N-dimethylaniline provides the doubly labeled chloropurine (XII), which is submitted to enzymatic trans-glycosylation with 7-methylguanosine or thymidine and purine nucleoside phosphorylase (PNP) and thymidine phosphorylase (TP) to give the glycosylated chloropurine (XIII). Finally, this compound is treated with 15NH4Cl and KHCO3 in hot anhydrous DMSO to afford the target triply labeled adenine nucleoside. Alternatively, the intermediate hypoxanthine (XI) can also be obtained directly by cyclization of the doubly labeled 5-amino-1H-imidazole-4-carboxamide (VIII) with formic acid and diethoxymethyl acetate (DEMA) in DMF.

1 Abad, J.-L.; Gaffney B.L.; Jones R.A.; 15N-multilabeled adenine and guanine nucleosides syntheses of [1,3,NH2-15N3]- and [2-13C-1,3NH2-15N3]-labeled adenosine, guanosine , 2'-deoxyadenosine, and 2'-deoxyguanosine. J Org Chem 1999, 64, 18, 6575.
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) 31951 1H-imidazole-4,5-dicarboxylic acid 570-22-9 C5H4N2O4 详情 详情
(II) 27424 3-(1-trityl-1H-imidazol-4-yl)-1-propanol C25H24N2O 详情 详情
(III) 51896 diethyl 2-bromo-1H-imidazole-4,5-dicarboxylate C9H11BrN2O4 详情 详情
(IV) 51897 2-bromo-1H-imidazole-4,5-dicarboxylic acid C5H3BrN2O4 详情 详情
(V) 51898 4-bromobenzenediazonium C6H4BrN2 详情 详情
(V) 51907 4-bromobenzenediazonium C6H4BrN2 详情 详情
(VI) 51899 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxylic acid C10H7BrN4O2 详情 详情
(VI) 51908 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxylic acid C10H7BrN4O2 详情 详情
(VII) 51900 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxamide C10H8BrN5O 详情 详情
(VII) 51909 2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxamide C10H8BrN5O 详情 详情
(VIII) 11015 5-Amino-1H-imidazole-4-carboxamide 360-97-4 C4H6N4O 详情 详情
(VIII) 51901 5-amino-1H-imidazole-4-carboxamide C4H6N4O 详情 详情
(IX) 51910   C3H5NaOS2 详情 详情
(X) 51911   C5H3N4NaOS 详情 详情
(X) 51913   C5H3N4NaOS 详情 详情
(XI) 51912 1,9-dihydro-6H-purin-6-one C5H4N4O 详情 详情
(XI) 51914 1,9-dihydro-6H-purin-6-one C5H4N4O 详情 详情
(XII) 17692 6-Chloropurine; 6-chloro-9H-purine 87-42-3 C5H3ClN4 详情 详情
(XII) 51915 6-chloro-9H-purine C5H3ClN4 详情 详情
(XIII) 18716 6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol 2004-06-0 C10H11ClN4O4 详情 详情
(XIII) 51916 (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol C10H11ClN4O4 详情 详情
Extended Information