【结 构 式】 |
【分子编号】27133 【品名】ethyl 2-[2-methyl-4-(trifluoromethyl)anilino]-2-oxoacetate 【CA登记号】 |
【 分 子 式 】C12H12F3NO3 【 分 子 量 】275.2274296 【元素组成】C 52.37% H 4.39% F 20.71% N 5.09% O 17.44% |
合成路线1
该中间体在本合成路线中的序号:(III)The reaction of 2-methyl-4-(trifluoromethyl)aniline (I) with ethoxalyl chloride (II) by means of triethylamine in ethyl acetate gives the oxamic ester (III), which is nitrated at the aromatic ring with KNO3 and H2SO4 yielding the intermediate (IV). The reductocyclization of (IV) by means of TiCl3 in acetone affords the quinoxalinedione (V), which is treated with PCl5 in refluxing POCl3 affording the dichloroquinoxaline (VI). The reaction of (VI) with sodium methoxide in refluxing methanol gives the dimethoxyquinoxaline (VII), which is brominated with NBS and AIBN in refluxing benzene yielding the bromomethyl quinoxaline (VIII). The condensation of (VIII) with dimethyl 1(S)-aminoethylphosphonate (IX) by means of NaHCO3 in DMF affords the phosphonate derivative (X), which is finally submitted to acid hydrolysis to provide the target compound.
【1】 Auberson, Y.P.; et al.; N-Phosphonoalkyl-5-aminomethylquinoxaline-2,3-diones: In vivo active AMPA and NMDA(glycine) antagonists. Bioorg Med Chem Lett 1999, 9, 2, 249. |
【2】 Acklin, P.; Allgeier, H.; Auberson, Y.; Ofner, S.; Veenstra, S.J. (Novartis AG); Substd. aminoalkane phosphonic acids. EP 0934326; US 6117873; WO 9817672 . |
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) | 27132 | 2-methyl-4-(trifluoromethyl)aniline | C8H8F3N | 详情 | 详情 | |
(II) | 11043 | Ethyl 2-chloro-2-oxoacetate; Ethyl oxalyl chloride | 4755-77-5 | C4H5ClO3 | 详情 | 详情 |
(III) | 27133 | ethyl 2-[2-methyl-4-(trifluoromethyl)anilino]-2-oxoacetate | C12H12F3NO3 | 详情 | 详情 | |
(IV) | 27134 | ethyl 2-[2-methyl-6-nitro-4-(trifluoromethyl)anilino]-2-oxoacetate | C12H11F3N2O5 | 详情 | 详情 | |
(V) | 27135 | 5-methyl-7-(trifluoromethyl)-1,4-dihydro-2,3-quinoxalinedione | C10H7F3N2O2 | 详情 | 详情 | |
(VI) | 27136 | 2,3-dichloro-5-methyl-7-(trifluoromethyl)quinoxaline | C10H5Cl2F3N2 | 详情 | 详情 | |
(VII) | 27137 | 2,3-dimethoxy-5-methyl-7-(trifluoromethyl)quinoxaline | C12H11F3N2O2 | 详情 | 详情 | |
(VIII) | 27138 | 5-(bromomethyl)-2,3-dimethoxy-7-(trifluoromethyl)quinoxaline | C12H10BrF3N2O2 | 详情 | 详情 | |
(IX) | 27139 | dimethyl (1S)-1-aminoethylphosphonate | C4H12NO3P | 详情 | 详情 | |
(X) | 27140 | dimethyl (1S)-1-([[2,3-dimethoxy-7-(trifluoromethyl)-5-quinoxalinyl]methyl]amino)ethylphosphonate | C16H21F3N3O5P | 详情 | 详情 |