Br.[Cl:2][C:3]1[C:12]([OH:13])=[C:11]([OH:14])[C:10]([Cl:15])=[C:9]2[C:4]=1[CH2:5][CH2:6][NH:7][CH2:8]2.[CH3:16][C:17]1[C:22](/[CH:23]=[CH:24]/[C:25](O)=[O:26])=[CH:21][CH:20]=[C:19]([C:28]([F:31])([F:30])[F:29])[N:18]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[Cl:2][C:3]1[C:12]([OH:13])=[C:11]([OH:14])[C:10]([Cl:15])=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]([C:25](=[O:26])/[CH:24]=[CH:23]/[C:22]1[C:17]([CH3:16])=[N:18][C:19]([C:28]([F:29])([F:30])[F:31])=[CH:20][CH:21]=1)[CH2:8]25,8-Dichloro-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydro bromide (183 mg, 0.58 mmol), (E)-3-(2-methyl-6-(trifluoromethyl)pyridin-3-yl)acrylic acid (140 mg, 0.64 mmol), EDC.HCl (167 mg, 0.87 mmol), HOBt (89 mg, 0.58 mmol), DMAP (147 mg, 1.2 mmol) and Cs2CO3 (391 mg, 1.2 mmol) were suspended in DMF (15 mL) and stirred at rt for 12 h. The reaction mixture was then diluted with water (30 mL) and extracted with EtOAc (3×30 mL). Combined organics were washed with NaHCO3 (2×30 mL, sat. aq.), water (3×30 mL) and brine and dried (MgSO4). After filtration and evaporation the residue was purified by column chromatography (SiO2, CH2Cl2:MeOH 95:5) and was then further purified by size exclusion chromatography (sephadex, CHCl3:MeOH 1:1) to give the title compound (28 mg, 63 μmol, 11%) as a yellow solid.
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