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【结 构 式】 
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【分子编号】58825 【品名】5-chloro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione 【CA登记号】 |
【 分 子 式 】C9H6ClNO3 【 分 子 量 】211.60428 【元素组成】C 51.09% H 2.86% Cl 16.75% N 6.62% O 22.68% |
合成路线1
该中间体在本合成路线中的序号：(II)5-Chloroisatoic anhydride (I) is alkylated with iodomethane and NaH to afford (II). Subsequent condensation of anhydride (II) with the malonic monoamide (III) in the presence of NaH in hot DMA furnishes the target quinoline carboxamide.
| 【1】 Bjork, A.; Jonsson, S.; Fex, T.; Hedlund, G. (Active Biotech AB); Quinoline derivs.. EP 1073639; JP 2002513006; US 6077851; WO 9955678 . |
合成路线2
该中间体在本合成路线中的序号：(III)Reaction of 2-amino-6-chlorobenzoic acid (I) with phosgene and NaHCO3 in dioxane gives 5-chloroisatoic anhydride (II), which is methylated by means of iodomethane and NaH in DMF to yield 5-chloro-1-methylisatoic anhydride (III). Finally, anhydride (III) is condensed with the malonic monoamide (IV) by means of NaH in hot dimethylacetamide. Alternatively, condensation of anhydride (III) with ethoxy malonyl chloride (V) by means of NaOMe and triethylamine in dichloromethane affords 5-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3- carboxylic acid ethyl ester (VI), which is finally condensed with N-ethylaniline (VII) in refluxing toluene. Alternatively, ester (VI) is hydrolyzed by means of concentrated HCl in hot Ac2O to give the carboxylic acid (VIII), which is finally condensed with N-ethylaniline (VII) by means of SOCl2 and TEA in dichloromethane
| 【1】 Sorbera, L.A.; Castaner, J.; Laquinimod. Drugs Fut 2003, 28, 11, 1059. |
| 【2】 Bjork, A.; Jonsson, S.; Fex, T.; Hedlund, G. (Active Biotech AB); Quinoline derivs.. EP 1073639; JP 2002513006; US 6077851; WO 9955678 . |
| 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) | 63056 | 2-amino-6-chlorobenzoic acid | C7H6ClNO2 | 详情 | 详情 | |
| (II) | 58824 | 5-chloro-2H-3,1-benzoxazine-2,4(1H)-dione | C8H4ClNO3 | 详情 | 详情 | |
| (III) | 58825 | 5-chloro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione | C9H6ClNO3 | 详情 | 详情 | |
| (IV) | 58826 | ethyl 3-(ethylanilino)-3-oxopropanoate | C13H17NO3 | 详情 | 详情 | |
| (V) | 13188 | ethyl 3-chloro-3-oxopropanoate; 2-Ethoxycarbonylacetyl chloride; Ethyl malonyl chloride | 36239-09-5 | C5H7ClO3 | 详情 | 详情 |
| (VI) | 63057 | ethyl 5-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydro-3-quinolinecarboxylate | C13H12ClNO4 | 详情 | 详情 | |
| (VII) | 63058 | N-ethyl-N-phenylamine; N-ethylaniline | C8H11N | 详情 | 详情 | |
| (VIII) | 63059 | 5-chloro-4-hydroxy-1-methyl-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid | C11H8ClNO4 | 详情 | 详情 |