[OH-].[Na+].[NH2:3][C:4]1[C:9]2=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([NH2:24])=[C:20]([F:25])[CH:19]=3)[C:11]([C:13]([O:15]CC)=[O:14])=[CH:12][N:8]2[N:7]=[CH:6][N:5]=1.Cl>C1COCC1.C(O)C>[NH2:3][C:4]1[C:9]2=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([NH2:24])=[C:20]([F:25])[CH:19]=3)[C:11]([C:13]([OH:15])=[O:14])=[CH:12][N:8]2[N:7]=[CH:6][N:5]=11 N aqueous sodium hydroxide (253 mL, 253 mmol) was added to a suspension of ethyl 4-amino-5-(4-amino-3-fluorophenyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (40.0 g, 127 mmol) in THF (400 mL) and ethanol (400 mL). The reaction mixture was heated (65° C.) for 16 h and then cooled to rt. Hydrogen chloride (4 N in 1,4-dioxane, 70 mL, 280 mmol) was added and the volatiles were removed under reduced pressure. The residue was washed with water (200 mL) and then triturated with acetone and diethyl ether to give the desired product (36.3 g 99%) containing trace impurities. 1H NMR (300 MHz, DMSO-d6) δ 12.20-12.30 (br s, 1H), 8.03 (s, 1H), 7.94-8.05 (br s, 1H), 7.89 (s, 1H), 7.02 (dd, J=12.4, 2.0 Hz, 1H), 6.73-6.92 (m, 2H), 5.22-5.47 (br s, 1H), 5.12-5.25 (br s, 1H); ES-MS m/z 288.0 (MH)+; HPLC RT (Method A) 1.13 min.
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