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【结 构 式】 
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【分子编号】51899 【品名】2-bromo-5-[(E)-2-phenyldiazenyl]-1H-imidazole-4-carboxylic acid 【CA登记号】 |
【 分 子 式 】C10H7BrN4O2 【 分 子 量 】295.09534 【元素组成】C 40.7% H 2.39% Br 27.08% N 18.99% O 10.84% |
合成路线1
该中间体在本合成路线中的序号：(VI)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2
该中间体在本合成路线中的序号：(VI)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 |