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【结 构 式】 
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【分子编号】54048 【品名】(1R)-2-[2-amino-4-(hydroxymethyl)anilino]-1-phenyl-1-ethanol 【CA登记号】 |
【 分 子 式 】C15H18N2O2 【 分 子 量 】258.3202 【元素组成】C 69.74% H 7.02% N 10.84% O 12.39% |
合成路线1
该中间体在本合成路线中的序号：(XII)The reduction of 4-fluoro-3-nitrobenzoic acid (I) with BH3/THF gives the benzyl alcohol (IX), which is condensed with 2(R)-hydroxy-2-phenylethylamine (V) by means of DIEA in NMP to yield nitro compound (XI). Derivative (XI) is then converted into secondary amine (XII) by reduction either with H2 over Pd/C in EtOH or with Na2S·9H2O in dioxane/H2O or by treatment with Na2S2O4 in dioxane/NH4OH. Cyclization of (XI) with 4-methoxybenzoyl isothiocyanate (VIII) by means of EDC in DMF affords the benzimidazole (XIII), which is oxidized at the carbinol group by means of MnO2 in THF to provide the corresponding carbaldehyde (XIV). Finally, this compound is reductocondensed with 1-methylpiperazine (II) by means of NaBH(OAc)3 to furnish the target benzimidazole.
| 【1】 Heyer, D.; et al.; 2-Aminobenzimidazoles: A class of orally bioavailable and brain permeable neuropeptide YY5 antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 284. |
| 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) | 46937 | 4-fluoro-3-nitrobenzoic acid | 453-71-4 | C7H4FNO4 | 详情 | 详情 |
| (II) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (V) | 10173 | (1R)-2-Amino-1-phenyl-1-ethanol | 2549-14-6 | C8H11NO | 详情 | 详情 |
| (VIII) | 54045 | 4-Methoxybenzoyl isothiocyanate | 16778-84-0 | C9H7NO2S | 详情 | 详情 |
| (IX) | 54046 | (4-fluoro-3-nitrophenyl)methanol | C7H6FNO3 | 详情 | 详情 | |
| (XI) | 54047 | (1R)-2-[4-(hydroxymethyl)-2-nitroanilino]-1-phenyl-1-ethanol | C15H16N2O4 | 详情 | 详情 | |
| (XII) | 54048 | (1R)-2-[2-amino-4-(hydroxymethyl)anilino]-1-phenyl-1-ethanol | C15H18N2O2 | 详情 | 详情 | |
| (XIII) | 54049 | N-{5-(hydroxymethyl)-1-[(2R)-2-hydroxy-2-phenylethyl]-1H-benzimidazol-2-yl}-4-methoxybenzamide | C24H23N3O4 | 详情 | 详情 | |
| (XIV) | 54050 | N-{5-formyl-1-[(2R)-2-hydroxy-2-phenylethyl]-1H-benzimidazol-2-yl}-4-methoxybenzamide | C24H21N3O4 | 详情 | 详情 |