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【结 构 式】 
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【分子编号】36066 【品名】2-(chloromethyl)-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepine 【CA登记号】 |
【 分 子 式 】C17H16ClFN2 【 分 子 量 】302.7786232 【元素组成】C 67.44% H 5.33% Cl 11.71% F 6.27% N 9.25% |
合成路线1
该中间体在本合成路线中的序号：(II)The cyclization of N1-(2-fluorobenzoyl)-N2-methyl-N2-phenyl-2-hydroxy-1,3-diaminopropane (I) with refluxing POCl3 gives 1-methyl-2-chloromethyl-5-(2-fluorophenyl)-1H-2,3-dihydro-1,4-benzodiazepine (II), which by condensation with potassium phthalimide (III) in refluxing methanol yields the corresponding phthalimido derivative (IV). The cleavage of (IV) with hydrazine in refluxing ethanol affords 1-methyl-2-aminomethyl-5-(2-fluorophenyl)-1H-2,3-dihydro-1,4-benzodiazepine (V), which is finally condensed with thiophene-3-carbonyl chloride (VI) by means of triethylamine in methylene chloride.
| 【1】 Zeugner, H.; Romer, D.; Liepmann, H.; Milkowski, W. (Kali-Chemie AG); 2-Acylaminomethyl-1,4-benzodiazepine derivs. and their salts and pharmaceutical compsns. thereof. US 4325957 . |
| 【2】 Serradell, M.N.; Paton, D.M.; Blancafort, P.; Castaner, J.; Tifluadom. Drugs Fut 1983, 8, 6, 519. |
| 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) | 36065 | 2-fluoro-N-[2-hydroxy-3-(methylanilino)propyl]benzamide | C17H19FN2O2 | 详情 | 详情 | |
| (II) | 36066 | 2-(chloromethyl)-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepine | C17H16ClFN2 | 详情 | 详情 | |
| (III) | 27890 | Potassium phthalimide | 1074-82-4 | C8H4KNO2 | 详情 | 详情 |
| (IV) | 36067 | 2-[[5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-yl]methyl]-1H-isoindole-1,3(2H)-dione | C25H20FN3O2 | 详情 | 详情 | |
| (V) | 36068 | [5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-yl]methanamine; [5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-yl]methylamine | C17H18FN3 | 详情 | 详情 | |
| (VI) | 36069 | 3-thiophenecarbonyl chloride | 41507-35-1 | C5H3ClOS | 详情 | 详情 |