反应详情

To a stirred solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-hydroxybutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide in dichloromethane (2 mL) was added drop-wise trifluoroacetic acid (1 mL) at room temperature and the reaction mixture was stirred for 1 hour. The solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and washed with NaHCO3 (aqueous), The organic layer was concentrated, and the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 36% acetonitrile/64% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 42% acetonitrile/58% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.) to give 2-(6-fluoro-1-(3-hydroxybutyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (10 mg, 45% over three steps) as a white solid. LCMS: (M+H)+=441; 1H NMR (300 MHz, CD3OD): δ 9.15 (s, 1H), 8.58 (dd, 1H, J1=9. Hz, J2=5.4 Hz), 8.29 (s, 1H), 7.42 (d, 1H, J=7.8 Hz), 7.10 (d, 1H, J=7.2 Hz), 4.62-4.56 (m, 2H), 3.82 (s, 2H), 3.76 (brs, 1H), 2.19-2.13 (m, 2H), 2.04-1.99 (m, 2H), 1.55 (s, 6H), 1.22 (d, 3H, J=6.3 Hz).

1. customThe solvent was removed under reduced pressure
2. dissolutionThe residue was dissolved in dichloromethane
3. washwashed with NaHCO3 (aqueous)
4. concentrationThe organic layer was concentrated
5. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
6. wait36% acetonitrile/64% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 42% acetonitrile/58% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.