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.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[NH:64]1[CH:68]=[N:67][C:66]([NH2:69])=[N:65]1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[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:69][C:66]2[N:67]=[CH:68][NH:64][N:65]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1To a mixture of 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)quinazoline from Example 4 Step A (100 mg, 0.32 mmol), Pd2(dibenzylideneacetone)3 (12 mg, 0.013 mmol), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (23 mg, 0.04 mmol), SEM protected 1,2,4-triazol-3-amine (97 mg, 0.45 mmol), and Na2CO3 (48 mg, 0.45 mmol) was added toluene (3 mL), and the mixture was evacuated and flushed with argon three times. The mixture was heated at 110° C. for 2 h, and then diluted with DCM and filtered. To the filtrate was added TFA (3 mL) and the mixture was stirred at rt for 2 h and then concentrated under reduced pressured. To the residue was added MeOH and the mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC (Phenomenex C-18 reverse phase column eluting with gradient of solvent B=0.05% HOAC/ACN and solvent A=0.05% HOAc/H2O). The obtained material was triturated with diethyl ether to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(1H-1,2,4-triazol-3-yl)quinazolin-4-amine (16 mg, 14%). 1H NMR (300 MHz, methanol-d4) δ 8.68 (br s, 1H), 8.50 (d, J=8.3 Hz, 1H), 7.90-8.15 (m, 4H), 7.71-7.88 (m, 2H). LCMS (ESI) m/z 358 (M+H)+.
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