Br[C:2]1[CH:3]=[C:4]2[CH2:10][C:9](=[O:11])[NH:8][C:5]2=[N:6][CH:7]=1.[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>CCO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[F:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:3]=[C:4]3[CH2:10][C:9](=[O:11])[NH:8][C:5]3=[N:6][CH:7]=2)[CH:16]=[CH:15][CH:14]=1A mixture of 4 (16.63 g, 78.5 mmol), 3-fluorophenylboronic acid (16.47 g, 117.7 mmol), Pd(PPh3)2Cl2 (2.73 g, 6.60 mmol), LiCl (9.95 g, 0.23 mol), 1.0 M aqueous Na2CO3 solution (196 mL, 0.196 mol) in EtOH (470 mL)—toluene (470 mL) was refluxed overnight. More Pd(PPh3)2Cl2 (1.30 g, 3.14 mmol) was added and reflux was continued for 24 h. The mixture was cooled, and the organic layer was separated and washed with brine (100 mL). The washings were combined with the aqueous layer and extracted with AcOEt (4×400 mL). Combined extracts were washed with brine, added to the organic layer and dried with MgSO4. The solution was concentrated to dryness in vacuum to give 26.98 g of brown semisolid, which was triturated with ether:hexane=1:1 (2×500 mL). The residue was dried in vacuum to afford 5 (16.85 g, 94%) as tan solid, which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 3.66 (s, 2H), 7.08 (dddd, J=8.4, 8.2, 2.4, 0.9 Hz, 1H), 7.22 (ddd, J=10.0, 2.4, 1.7 Hz, 1H), 7.30 (ddd, J=8.1, 1.7, 0.9 Hz, 1H), 7.43 (ddd, J=8.2, 8.1, 6.0 Hz, 1H), 7.69 (s, 1H), 8.36 (d, J=2.1 Hz, 1H), 8.98 (bs, 1H).
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