[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([CH:12]=[C:13]([CH:16]=O)[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].[CH3:27][S:28][CH2:29][CH2:30][CH2:31][O:32][NH2:33]>C(Cl)Cl.CO>[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:33]/[O:32][CH2:31][CH2:30][CH2:29][S:28][CH3:27])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]The title compound was obtained by a procedure similar to that in Step B of Example 9 using 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide obtained in Step F of Example 1 as a starting material and O-(3-methylsulfanyl-propyl)-hydroxylamine obtained in Step B as a reagent. Namely, 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (76 mg, 0.158 mmol) was dissolved in a mixed solvent of methylene chloride (5 mL) and methanol (1 mL). O-(3-Methylsulfanyl-propyl)-hydroxylamine (100 μL) was added thereto, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, the solvent was evaporated under reduced pressure to give a pale yellow crude product. The residue was triturated with a proper amount of ethyl acetate:hexane (1:9) to give (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylsulfanyl-propoxyimino)-methyl]-benzamide (88.8 mg, 96%) as a white solid.
불러오는 중…