[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]#[N:28])[CH:22]=3)=[O:19])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(C1C=C(NC(=O)N)C=CC=1)#N.[NH:41]1[CH2:46][CH2:45][CH:44]([OH:47])[CH2:43][CH2:42]1>Cl.O1CCOCC1.CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([C:11]2[CH:12]=[CH:13][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([N:41]4[CH2:46][CH2:45][CH:44]([OH:47])[CH2:43][CH2:42]4)=[NH:28])[CH:22]=3)=[O:19])=[CH:15][CH:16]=2)(=[O:10])=[O:9])=[CH:6][CH:7]=1Under argon atmosphere, 1 equivalent of 1-(4-(4-bromophenylsulfonyl)phenyl)-3-(3-cyanophenyl)urea (VIII) [or a correspondent 14444-substituted-phenylsulfonyl)phenyl)-3-(3-cyanophenyl)urea] was dissolved in of 4 M HCl in dioxane/MeOH 5:1. The solution was stirred overnight at rt then the solvent was removed in vacuo. The residue was washed with diethylether, dried in vacuo, dissolved in dry MeOH (or DMF) and reacted with 1.1 to 2 equivalents of piperidin-4-ol (or 1.1 to 2 equivalents of the corresponding secondary amine) at temperature between 55 and 70° C. for a minimum of 4 h to a maximum of 22 h. The products were purified either by flash chromatography, using a silica gel column and an appropriate gradient of MeOH in DCM as eluent, or by preparative HPLC, using a reverse-phase column and a gradient of acetonitrile in 0.1% HCOOHaq.
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