Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([F:21])([F:20])[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH:31]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32]1.CC(O)=O>CN(C=O)C>[F:20][C:12]([F:21])([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[C:4]1[N:3]=[C:2]([NH:36][C:33]2[CH:34]=[CH:35][NH:31][N:32]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1To 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline (100 mg, 0.32 mmol) was added a solution of KI (20 mg, 0.12 mmol), DIEA (0.068 mL, 0.39 mmol), and 1H-pyrazol-3-amine (40 mg, 0.48 mmol) in DMF (2 mL). The mixture was stirred overnight at rt. AcOH (0.14 mL) was added and the mixture was purified by preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=0.05% AcOH/H2O) to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(1H-pyrazol-3-yl)quinazolin-4-amine (15 mg, 13%). 1H NMR (300 MHz, DMSO-d6) δ 12.52 (br s, 1H), 10.82 (br s, 1H), 8.53-8.86 (m, 2H), 7.77-8.13 (m, 4H), 7.57-7.74 (m, 2H), 6.50 (br s, 1H); LC-MS (ESI) m/z 357 (M+H)+.
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