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【结 构 式】 
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【分子编号】15466 【品名】2,4,6-Trichloroaniline; 2,4,6-Trichlorophenylamine 【CA登记号】634-93-5 |
【 分 子 式 】C6H4Cl3N 【 分 子 量 】196.4626 【元素组成】C 36.68% H 2.05% Cl 54.14% N 7.13% |
合成路线1
该中间体在本合成路线中的序号：(II)4-Chloro-2-methylphenol (I) is condensed with 2,4,6-trichloroaniline (II) by heating to 120-140 C with amyl nitrite for 18 hours. The excess phenol is removed in vacuo; the residue is adsorbed on silica gel, applied to the top of a silica gel column and the crude phenolic fraction isolated by elution with hexane/acetone (95:5). The phenolic fraction, which contains 2-methyl-2'4,4',6-tetrachlorobiphenylol (III) and other isomers, is dissolved in dimethyl sulfoxide, anhydrous sodium carbonate is added, and the mixture is then heated with stirring at 160 C for 2 hours. The cyclization product, 1,3,8-trichloro-6-methyldibenzofuran (MCDF) is isolated by column chromatography and further purified by crystallization from methanol or methanol/anisole.
| 【1】 Safe, S.H.; MCDF. Drugs Fut 1992, 17, 7, 564. |
合成路线2
该中间体在本合成路线中的序号：(II)The condensation of 4,6-dichloro-2-methylpyrimidine (I) with 2,4,6-trichloroaniline (II) by means of NaH in THF gives N-(6-chloro-2-methylpyrimidin-4-yl)-N-(2,4,6-trichlorophenyl)amine (III), which is condensed with N-(cyclopropylmethyl)-N-propylamine (IV) by heating at 100-190 C yielding N-(cyclopropylmethyl)-N-[2-methyl-6-(2,4,6-trichlorophenylamino)-pyrimidin-4-yl]-N-propylamine (V). Finally, this compound is chlorinated with N-chlorosuccinimide (NCS) in refluxing chloroform.
| 【1】 Dagnino, R. jr.; Chen, C.; de Souzza, E.B.; et al.; Design and synthesis of a series of non-peptide high-affinity human corticotropin-releasing factor1 receptor antagonists. J Med Chem 1996, 39, 22, 4360. |
| 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) | 32323 | 4,6-dichloro-2-methylpyrimidine | 1780-26-3 | C5H4Cl2N2 | 详情 | 详情 |
| (II) | 15466 | 2,4,6-Trichloroaniline; 2,4,6-Trichlorophenylamine | 634-93-5 | C6H4Cl3N | 详情 | 详情 |
| (III) | 32324 | N-(6-chloro-2-methyl-4-pyrimidinyl)-N-(2,4,6-trichlorophenyl)amine; 6-chloro-2-methyl-N-(2,4,6-trichlorophenyl)-4-pyrimidinamine | C11H7Cl4N3 | 详情 | 详情 | |
| (IV) | 27745 | N-(cyclopropylmethyl)-1-propanamine | 26389-60-6 | C7H15N | 详情 | 详情 |
| (V) | 32325 | N-(cyclopropylmethyl)-N-[2-methyl-6-(2,4,6-trichloroanilino)-4-pyrimidinyl]-N-propylamine; N(4)-(cyclopropylmethyl)-2-methyl-N(4)-propyl-N(6)-(2,4,6-trichlorophenyl)-4,6-pyrimidinediamine | C18H21Cl3N4 | 详情 | 详情 |