[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][O:23][CH2:24][CH3:25])[N:14]([CH2:15][C:16]3([OH:21])[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[N:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C(O)CC.O>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][O:23][CH2:24][CH3:25])[N:14]([CH2:15][C:16]3([OH:21])[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[N:8]=[CH:7][C:6]([C:31]3[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=3)=[CH:5][C:4]=2[N:3]=11-{[4-Amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol (1.13 g, 2.7 mmol), 4-fluorobenzeneboronic acid (0.43 g, 3.1 mmol), triphenylphosphine (6.3 mg, 0.024 mmol), and 5:1 (v/v) 1-propanol/water (6.6 mL) were combined under a nitrogen atmosphere. A 5 mg/mL solution of palladium (II) acetate (1.8 mg, 0.008 mmol) in toluene and aqueous sodium carbonate (1.8 mL of 2 M) were sequentially added. The reaction mixture was heated at reflux for two hours, allowed to cool to room temperature, and partitioned between chloroform (75 mL) and brine (20 mL). The organic fraction was separated, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue (1.27 g) was purified by trituration with acetonitrile at 98° C. followed by recrystallization from chloroform/hexane. The crystals were dried in a vacuum oven at 110 C for two hours to provide 0.67 g of 1-{[4-amino-2-(ethoxymethyl)-7-(4-fluorophenyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]methyl}cyclopentanol as a steel-gray solid, mp 212-212.5° C.
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