Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH2:9]2)[C:5]([F:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=1)[C:25]([NH:27][CH3:28])=[O:26].FC(F)(F)C(O)=O>CC(O)C>[F:20][C:5]1[C:6]([N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH2:9]2)=[N:7][C:2]([NH:21][C:22]2[CH:23]=[C:24]([CH:29]=[CH:30][CH:31]=2)[C:25]([NH:27][CH3:28])=[O:26])=[N:3][CH:4]=1To 2-chloro-5-fluoro-4-(3-(4-fluorophenoxy)azetidin-1-yl)pyrimidine (90.0 mg, 0.302 mmol) and 3-amino-N-methylbenzamide (49.9 mg, 0.333 mmol) in a disposable sealed tube in 2-propanol (2.50 mL) was added trifluoroacetic acid (0.070 mL, 0.907 mmol). The resulting reaction mixture was heated at 84° C. for 3 d, cooled to RT and concentrated. The residue was stirred in EtOAc and saturated aqueous NaHCO3 for 10 min and transferred to a reparatory funnel. The organic layer was washed with brine, dried and concentrated giving 3-(5-fluoro-4-(3-(4-fluorophenoxy)azetidin-1-yl)pyrimidin-2-ylamino)-N-methylbenzamide (124.8 mg).
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