Borane;tetrahydrofuran → N-(3-chloro-4-fluorophenyl)-6-((methyl(2,2,2-trifluoroethyl)amino)methyl)-2-(pyridin-3-yl)quinazolin-4-amine
Reaktionsgleichung
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]([N:22]([CH3:28])[CH2:23][C:24]([F:27])([F:26])[F:25])=O)[CH:18]=3)[N:13]=[C:12]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].B.C1COCC1>CO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([CH2:20][N:22]([CH3:28])[CH2:23][C:24]([F:27])([F:25])[F:26])[CH:18]=3)[N:13]=[C:12]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]Komponenten
4
Versuchsvorschrift
To a mixture of 4-(3-chloro-4-fluorophenylamino)-N-methyl-2-(pyridin-3-yl)-N-(2,2,2-trifluoroethyl)quinazoline-6-carboxamide (60 mg, 0.12 mmol) THF (1 mL) was added BH3-THF (2 mol/L, 1 mL). The mixture was stirred at room temperature overnight. Methanol (0.2 mL) was added to quench the reaction mixture. The mixture was purified by prep-HPLC to give the desired product N-(3-chloro-4-fluorophenyl)-6-((methyl(2,2,2-trifluoroethyl)amino)methyl)-2-(pyridin-3-yl)quinazolin-4-amine (GL0001H-3309) as a white solid 15 mg in a yield of 26.0%. LCMS: r.t=2.154 min, [MH]+=476.1. 1H-NMR (400 MHz, DMSO-d6): δ 10.09 (s, 1H), 9.53 (s, 1H), 8.70-8.66 (m, 2H), 8.44 (s, 1H), 8.27-8.25 (m, 1H), 7.93-7.91 (m, 3H), 7.57-7.55 (m, 2H), 3.93 (s, 2H), 3.39-3.32 (m, 2H), 2.40 (s, 3H).