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【结 构 式】 
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【分子编号】47750 【品名】2-amino-4-methyl-3-nitrophenylamine; 4-methyl-3-nitro-1,2-benzenediamine 【CA登记号】 |
【 分 子 式 】C7H9N3O2 【 分 子 量 】167.16748 【元素组成】C 50.3% H 5.43% N 25.14% O 19.14% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The requisite nitrodiamine (VIII) was prepared via conversion of 4-methyl-1,2-phenylenediamine (V) to the selenocycle (VI) upon treatment with SeO2 and HCl, followed by nitration to afford regioselectively the nitro derivative (VII). Conversion to the diamine (VIII) was effected by treatment of (VII) with HI. Subsequent reaction of (VIII) with 2,4-pentanedione (IX) in the presence of HCl gave rise to the benzimidazole (X). Alkylation of (X) with bromide (IV) using K2CO3 in DMF provided adduct (XI) as the major regioisomer. Catalytic hydrogenation of the nitro group of (XI) then gave amine (XII). Finally, coupling of amine (XII) with 4'-(trifluoromethyl)biphenyl-2-carboxylic acid (XIII) was achieved via EDC activation or by previous conversion of (XIII) to the corresponding acid chloride with oxalyl chloride.
| 【1】 Sun, C.-Q.; Robl, J.A.; Sulsky, R.; et al.; A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. J Med Chem 2001, 44, 6, 851. |
| 【3】 Sulsky, R.B.; Poss, M.A.; Slusarchyk, W.A.; Dickson, J.K.; Biller, S.A.; Tino, J.A.; Magnin, D.R.; Lawrence, R.M.; Robl, J.A.; Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method. US 5760246 . |
| 【2】 Biller, S.A.; Dickson, J.K.; Lawrence, R.M.; Magnin, D.R.; Poss, M.A.; Robl, J.A.; Slusarchyk, W.A.; Sulsky, R.B.; Tino, J.A. (Bristol-Myers Squibb Co.); Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method. EP 0904262; JP 2000502355; WO 9726240 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 47746 | 9-(4-bromobutyl)-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide | C20H19BrF3NO | 详情 | 详情 | |
| (V) | 47747 | 4-methyl-1,2-benzenediamine; 2-amino-4-methylphenylamine; 3,4-Diaminotoluene; 3,4-Toluenediamine; 4-methyl-1,2-phenylenediamine; 4-Methyl-O-Phenylenediamine; asym-o-Tolylenediamine; o-Toluylenediamine; ortho-toluenediamine; Tolylene-3,4-diamine | 496-72-0 | C7H10N2 | 详情 | 详情 |
| (VI) | 47748 | 5-methyl-2,1,3-benzoselenadiazole | C7H6N2Se | 详情 | 详情 | |
| (VII) | 47749 | 5-methyl-4-nitro-2,1,3-benzoselenadiazole | C7H5N3O2Se | 详情 | 详情 | |
| (VIII) | 47750 | 2-amino-4-methyl-3-nitrophenylamine; 4-methyl-3-nitro-1,2-benzenediamine | C7H9N3O2 | 详情 | 详情 | |
| (IX) | 11620 | 2,4-Pentanedione;acetylacetone | 123-54-6 | C5H8O2 | 详情 | 详情 |
| (X) | 47751 | 2,5-dimethyl-4-nitro-1H-benzimidazole | C9H9N3O2 | 详情 | 详情 | |
| (XI) | 47752 | 9-[4-(2,5-dimethyl-4-nitro-1H-benzimidazol-1-yl)butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide | C29H27F3N4O3 | 详情 | 详情 | |
| (XII) | 47753 | 9-[4-(4-amino-2,5-dimethyl-1H-benzimidazol-1-yl)butyl]-N-(2,2,2-trifluoroethyl)-9H-fluorene-9-carboxamide | C29H29F3N4O | 详情 | 详情 | |
| (XIII) | 41132 | 4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxylic acid | C14H9F3O2 | 详情 | 详情 |