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【结 构 式】 
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【分子编号】20910 【品名】diethyl 2-[[[2-(acetoxy)acetyl]sulfanyl](2,3,4-trifluoroanilino)methylene]malonate 【CA登记号】 |
【 分 子 式 】C18H18F3NO7S 【 分 子 量 】449.4046696 【元素组成】C 48.11% H 4.04% F 12.68% N 3.12% O 24.92% S 7.14% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 2,3,4-trifluoroaniline (I) with carbon disulfide and triethylamine gives triethylammonium N-(2,3,4-trifluorophenyl)dithiocarbamate (II), which by reaction with ethyl chlorocarbonate in chloroform yields the corresponding isothiocyanate (III). The condensation of (III) with diethyl malonate (IV) by means of NaH in THF affords the sodium salt of diethyl [(2,3,4-trifluoroanilino)(mercapto)methylene]malonate (V), which is condensed with 1-acetoxy-3-chloroacetone in DMF to give the substituted thioester (VII). The cyclization of (VII) by means of sulfuric acid yields the thiazoline derivative (VIII), which is cyclized again by means of NaH in refluxing dioxane to afford diethyl (6,7-difluoro-1H,4H-thiazolo[4,3-c][1,4]benzoxazin-1-ylidene)malonate (IX). A final, new cyclization of (IX) by means of ethyl polyphosphate (PPE) at 138 C, followed by hydrolysis of the intermediate ester with sulfuric acid gives 7,8-difluoro-9,1-epoxymethano-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid (X). This compound is then condensed with 1-methylpiperazine (XI) in hot DMSO and treated with aqueous HCl.
| 【1】 Taguchi, M.; Kondo, H.; Inoue, Y.; Kawahata, Y.; Tsukamoto, G. (Kanebo Pharmaceuticals, Ltd.); Quinolinecarboxylic acid derivs., a compsns. comprising the same, process for preparing the same, and the use of the same for the manufacture of medicaments. EP 0286089; JP 1989199979; US 4808584 . |
| 【2】 Prous, J.; Castaner, J.; KB-5246. Drugs Fut 1989, 14, 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) | 13059 | 2,3,4-Trifluorophenylamine; 2,3,4-Trifluoroaniline | 3862-73-5 | C6H4F3N | 详情 | 详情 |
| (II) | 20905 | N,N-dipropyl-1-propanaminium 2,3,4-trifluorophenylcarbamodithioate | C16H25F3N2S2 | 详情 | 详情 | |
| (III) | 20906 | 1,2,3-trifluoro-4-isothiocyanatobenzene; 2,3,4-trifluorophenyl isothiocyanate | 119474-40-7 | C7H2F3NS | 详情 | 详情 |
| (IV) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (V) | 20908 | sodium 3-ethoxy-2-(ethoxycarbonyl)-3-oxo-1-(2,3,4-trifluoroanilino)-1-propene-1-thiolate | C14H13F3NNaO4S | 详情 | 详情 | |
| (VI) | 20909 | 4-chloro-3-oxobutyl acetate | C6H9ClO3 | 详情 | 详情 | |
| (VII) | 20910 | diethyl 2-[[[2-(acetoxy)acetyl]sulfanyl](2,3,4-trifluoroanilino)methylene]malonate | C18H18F3NO7S | 详情 | 详情 | |
| (VIII) | 20911 | diethyl 2-[4-(hydroxymethyl)-3-(2,3,4-trifluorophenyl)-1,3-thiazol-2(3H)-ylidene]malonate | C17H16F3NO5S | 详情 | 详情 | |
| (IX) | 13066 | diethyl 2-(6,7-difluoro-4H-[1,3]thiazolo[4,3-c][1,4]benzoxazin-1-ylidene)malonate | C17H15F2NO5S | 详情 | 详情 | |
| (X) | 13068 | 5,6-Difluoro-8-oxo-3H,8H-4-oxa-1-thia-9b-azacyclopenta[cd]phenalene-9-carboxylic acid | C13H5F2NO4S | 详情 | 详情 | |
| (XI) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |