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【结 构 式】 
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【分子编号】47957 【品名】2-hydrazinobenzoic acid 【CA登记号】52356-01-1 |
【 分 子 式 】C7H8N2O2 【 分 子 量 】152.1528 【元素组成】C 55.26% H 5.3% N 18.41% O 21.03% |
合成路线1
该中间体在本合成路线中的序号：(II)The condensation between 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione (I) and 2-hydrazinobenzoic acid (II) in refluxing HOAc afforded the pyrazole derivative (III). After conversion of (III) into the corresponding acid chloride (IV) by using SOCl2, treatment with ammonium hydroxide provided amide (V). Dehydration of amide (V) employing trichloroacetyl chloride and Et3N yielded nitrile (VI), which was reduced to the primary amine (VII) with NaBH4 and CoCl2. After protection of the amino group of (VII) as the N-Boc derivative (VIII), oxidative cleavage of the furan ring with KMnO4 produced the carboxylic acid (IX), which was further activated as the acid chloride (X) upon treatment with oxalyl chloride.
| 【1】 Bostrom, L.L.; Pinto, D.J.P.; Galemmo, R.A. Jr.; Rossi, K.A. (DuPont Pharmaceuticals Co.); Nitrogen containing heteroaromatics with ortho-substd. P1's as factor Xa inhibitors. EP 1042299; WO 9932454 . |
| 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) | 47956 | 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione; 1-(2-Furanyl)-4,4,4-trifluoro-1,3-butanedione | 326-90-9 | C8H5F3O3 | 详情 | 详情 |
| (II) | 47957 | 2-hydrazinobenzoic acid | 52356-01-1 | C7H8N2O2 | 详情 | 详情 |
| (III) | 47958 | 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoic acid | C15H9F3N2O3 | 详情 | 详情 | |
| (IV) | 47958 | 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoic acid | C15H9F3N2O3 | 详情 | 详情 | |
| (V) | 47959 | 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoyl chloride | C15H8ClF3N2O2 | 详情 | 详情 | |
| (VI) | 47960 | 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzamide | C15H10F3N3O2 | 详情 | 详情 | |
| (VII) | 47961 | 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile | C15H8F3N3O | 详情 | 详情 | |
| (VIII) | 47962 | 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylamine; [2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]methanamine | C15H12F3N3O | 详情 | 详情 | |
| (IX) | 47963 | tert-butyl 2-[5-(2-furyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylcarbamate | C20H20F3N3O3 | 详情 | 详情 | |
| (X) | 47964 | 1-(2-[[(tert-butoxycarbonyl)amino]methyl]phenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid | C17H18F3N3O4 | 详情 | 详情 | |
| (XI) | 47965 | tert-butyl 2-[5-(chlorocarbonyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzylcarbamate | C17H17ClF3N3O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The condensation between 5-chloro-3(2H)benzofuranone (I) and 2-hydrazinobenzoic acid (II) afforded the corresponding hydrazone (III). This was subjected to microwave-promoted Fischer indole cyclization in formic acid to produce the target benzofuroindole tetracyclic system.
| 【1】 Butera, J.A.; et al.; Synthesis and potassium channel opening activity of substituted 10H-benzo[4,5]furo[3,2-b]indole- and 5,10-dihydro-indeno[1,2-b]indole-1-carboxylic acids. Bioorg Med Chem Lett 2001, 11, 16, 2093. |
| 【2】 Butera, J.A.; Antane, S.A.; Lennox, J.R. (Wyeth); Substd. benzofuranoindoles and indenoindoles as novel potassium channel openers. EP 1135393; US 6288099; WO 0034285 . |