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【结 构 式】 
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【分子编号】43215 【品名】ethyl (E)-3-(cyclopropylamino)-3-(methylsulfanyl)-2-(2,4,5-trifluorobenzoyl)-2-propenoate 【CA登记号】 |
【 分 子 式 】C16H16F3NO3S 【 分 子 量 】359.3691896 【元素组成】C 53.48% H 4.49% F 15.86% N 3.9% O 13.36% S 8.92% |
合成路线1
该中间体在本合成路线中的序号：(IVb)The condensation of 2-(2,4,5-trifluorobenzoyl)acetic acid ethyl ester (I) with cyclopropyl isothiocyanate (II) by means of NaH in DMF gives the sodium salt (IIIa-b), which is methylated with methyl iodide to afford the methylsulfanyl derivative (IVa-b). The cyclization of (IVa-b) by means of NaH in THF provides the methylsulfanyl quinolone (V), which is oxidized with MCPBA to the corresponding methylsulfinyl compound (VI). The reaction of (VI) with NaSH in THF furnishes 1-cyclopropyl-6,7-difluoro-4-oxo-2-sulfanyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (VII), which is cyclized with hydroxylamine-O-sulfonic acid and NaHCO3 through the intermediate (VIII), affording the isothiazoloquinoline (IX). Finally, this compound is condensed with piperazine (X) in pyridine to give the target compound.
| 【1】 Chu, D.T.W.; Isothiazoloquinolones: Antibacterial and antineoplastic agents. Drugs Fut 1992, 17, 12, 1101. |
| 【2】 Aquilar-Bryan, L.; Bryan, J.; Boyd, A.E. III; et al.; Sulfonylurea signal transduction. Recent Prog Horm Res 1991, 47, 299-317. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IIIa) | 43212 | sodium (Z)-1-(cyclopropylamino)-3-ethoxy-3-oxo-2-(2,4,5-trifluorobenzoyl)-1-propene-1-thiolate | C15H13F3NNaO3S | 详情 | 详情 | |
| (IIIb) | 43213 | sodium (E)-1-(cyclopropylamino)-3-ethoxy-3-oxo-2-(2,4,5-trifluorobenzoyl)-1-propene-1-thiolate | C15H13F3NNaO3S | 详情 | 详情 | |
| (IVa) | 43214 | ethyl (Z)-3-(cyclopropylamino)-3-(methylsulfanyl)-2-(2,4,5-trifluorobenzoyl)-2-propenoate | C16H16F3NO3S | 详情 | 详情 | |
| (IVb) | 43215 | ethyl (E)-3-(cyclopropylamino)-3-(methylsulfanyl)-2-(2,4,5-trifluorobenzoyl)-2-propenoate | C16H16F3NO3S | 详情 | 详情 | |
| (I) | 22096 | ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate | C11H9Cl2FO3 | 详情 | 详情 | |
| (II) | 43211 | 1-isothiocyanatocyclopropane; cyclopropyl isothiocyanate | 56601-42-4 | C4H5NS | 详情 | 详情 |
| (V) | 43216 | ethyl 1-cyclopropyl-6,7-difluoro-2-(methylsulfanyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C16H15F2NO3S | 详情 | 详情 | |
| (VI) | 43217 | ethyl 1-cyclopropyl-6,7-difluoro-2-(methylsulfinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C16H15F2NO4S | 详情 | 详情 | |
| (VII) | 43218 | ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-2-sulfanyl-1,4-dihydro-3-quinolinecarboxylate | C15H13F2NO3S | 详情 | 详情 | |
| (VIII) | 43219 | ethyl 2-(aminosulfanyl)-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydro-3-quinolinecarboxylate | C15H14F2N2O3S | 详情 | 详情 | |
| (IX) | 43220 | 9-cyclopropyl-6,7-difluoroisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione | C13H8F2N2O2S | 详情 | 详情 | |
| (X) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |