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【结 构 式】 
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【分子编号】61539 【品名】N-(3-amino-4-pyridinyl)-N-cyclopropylamine; N~4~-cyclopropyl-3,4-pyridinediamine 【CA登记号】 |
【 分 子 式 】C8H11N3 【 分 子 量 】149.19556 【元素组成】C 64.4% H 7.43% N 28.16% |
合成路线1
该中间体在本合成路线中的序号：(XII)Synthesis of benzimidazole intermediate (VIII) was achieved as follows. The reaction of 2,5-difluoronitrobenzene (I) with 3-methoxypropylamine (II) by means of K2CO3 in acetonitrile gives the aniline (III), which is reduced with Fe and NH4Cl in water to yield the phenylenediamine (IV). The cyclization of (IV) with glycolic acid (V) in refluxing 4N HCl affords the benzimidazolylmethanol (VI). Finally, this compound is brominated with (bromomethylene)dimethylammonium bromide (VII) in acetonitrile to provide the target bromomethylbenzimidazole intermediate (VIII). The reaction of 4-methoxy-3-nitropyridine (IX) with cyclopropylamine (X) in refluxing ethanol gives the N-cyclopropyl-3-nitropyridine-4-amine (XI), which is reduced with H2 over Pd/C in methanol to yield the pyridinediamine (XII). The cyclization of (XII) with phosgene in acetonitrile affords 1-cyclopropyl-2,3-dihydro-1H-imidazol[4,5-c]pyridin-2-one (XIII), which is condensed with bromomethyl intermediate (VIII) by means of NaH in THF, DMF or acetonitrile to provide the adduct (XIV). Finally, this compound is demethylated by means of BBr3 in dichloromethane to furnish the target 3-hydroxypropyl compound.
| 【1】 Meanwell, N.A.; Yu, K.-L.; Combrink, K.D.; Wang, X.; Civiello, R.L.; Gulgeze, H.B.; Sin, N.; Venables, B.L. (Bristol-Myers Squibb Co.); Imidazopyridine and imidazopyrimidine antiviral agents. EP 1311268; US 2002016309; US 6489338; WO 0195910 . |
| 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) | 28544 | 1,4-difluoro-2-nitrobenzene | 364-74-9 | C6H3F2NO2 | 详情 | 详情 |
| (II) | 61531 | Carbo-trap(TM) 2; 3-Methoxypropylamine; 1-Propanamine, 3-methoxy-; 3-Methoxy-1-aminopropane; 3-Methoxypropane-1-amine; 1-Amino-3-methoxypropane; 3-Methoxypropylamine; 3-Methoxypropyl-1-amine; 3-Aminopropyl Methyl Ether; 3-Methoxypropylamine with G.C.; 3-Methoxy Propylamine; 3-Methoxy-1-propanamine; 3MOPA | 5332-73-0 | C4H11NO | 详情 | 详情 |
| (III) | 61532 | 4-fluoro-N-(3-methoxypropyl)-2-nitroaniline; N-(4-fluoro-2-nitrophenyl)-N-(3-methoxypropyl)amine | C10H13FN2O3 | 详情 | 详情 | |
| (IV) | 61533 | N-(2-amino-4-fluorophenyl)-N-(3-methoxypropyl)amine; 4-fluoro-N~1~-(3-methoxypropyl)-1,2-benzenediamine | C10H15FN2O | 详情 | 详情 | |
| (V) | 29856 | 2-hydroxyacetic acid;glycolic acid | 79-14-1 | C2H4O3 | 详情 | 详情 |
| (VI) | 61534 | [1-(3-methoxypropyl)-1H-benzimidazol-2-yl]methanol | C12H16N2O2 | 详情 | 详情 | |
| (VII) | 61535 | N-(bromomethylene)-N-methylmethanaminium bromide | C3H7Br2N | 详情 | 详情 | |
| (VIII) | 61536 | 2-(bromomethyl)-1-(3-methoxypropyl)-1H-benzimidazole; 3-[2-(bromomethyl)-1H-benzimidazol-1-yl]propyl methyl ether | C12H15BrN2O | 详情 | 详情 | |
| (IX) | 61537 | 4-methoxy-3-nitropyridine; methyl 3-nitro-4-pyridinyl ether | C6H6N2O3 | 详情 | 详情 | |
| (X) | 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 |
| (XI) | 61538 | N-cyclopropyl-3-nitro-4-pyridinamine; N-cyclopropyl-N-(3-nitro-4-pyridinyl)amine | C8H9N3O2 | 详情 | 详情 | |
| (XII) | 61539 | N-(3-amino-4-pyridinyl)-N-cyclopropylamine; N~4~-cyclopropyl-3,4-pyridinediamine | C8H11N3 | 详情 | 详情 | |
| (XIII) | 61540 | 1-cyclopropyl-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one | C9H9N3O | 详情 | 详情 | |
| (XIV) | 61541 | 1-cyclopropyl-3-{[1-(3-methoxypropyl)-1H-benzimidazol-2-yl]methyl}-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one | C21H23N5O2 | 详情 | 详情 |