[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]1[C:14]([Cl:15])=[CH:13][C:12]([O:16][CH3:17])=[C:11]([NH:18][CH2:19][C:20]([OH:22])=O)[CH:10]=1.CCN(CC)CC.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.[C:53]([N:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH:58]1[C:63]([NH2:65])=[O:64])(=[O:56])[CH:54]=[CH2:55]>CN(C=O)C>[C:53]([N:57]1[CH2:62][CH2:61][N:60]([C:20](=[O:22])[CH2:19][NH:18][C:11]2[CH:10]=[C:9]([C:3]3[CH:4]=[C:5]([Cl:8])[CH:6]=[CH:7][C:2]=3[Cl:1])[C:14]([Cl:15])=[CH:13][C:12]=2[O:16][CH3:17])[CH2:59][CH:58]1[C:63]([NH2:65])=[O:64])(=[O:56])[CH:54]=[CH2:55]2-((2′,5′,6-Trichloro-4-methoxy-[1,1′-biphenyl]-3-yl)amino)acetic acid (231 mg, 0.641 mmol) and Et3N (592 mg, 2.564 mmol) in DMF (3 mL) at 0° C., EDCI.HCl (184 mg, 0.961 mmol) and HOBt (134 mg, 0.961 mmol) were added and the resulting mixture was stirred at 0° C. for 30 min. To this mixture, the above 1-acryloylpiperazine-2-carboxamide hydrochloride (160 mg) was added and stirred at room temperature for 16 h. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (DCM/MeOH=30:1) to afford the desired product (10 mg, 2.97% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 7.60-7.38 (m, 3H), 6.70-6.99 (m, 1H), 6.86-6.78 (m, 1H), 6.54-6.49 (m, 1H), 6.16-6.10 (m, 1H), 5.76-5.69 (m, 1H), 5.32-5.31 (m, 1H), 4.93-4.84 (m, 1H), 4.93-4.84 (m, 1H), 4.70-4.62 (m, 1H), 4.35-4.32 (m, 1H), 4.04-3.96 (m, 2H), 3.89-3.63 (m, 1H), 2.90-2.86 (m, 1H). ESI-MS m/z: 525.2[M+H]+.
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