反应详情

温度

25 °C

In a 16×100 mm screw cap test tube were added HATU (34.5 mg, 90.7 μmol.20), (4-aminotetrahydro-2H-pyran-4-yl)methanol (39.7 mg, 302 μmol) and 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (37 mg, 75.6 μmol) then the mixture was dissolved in DMF (3 mL) to give a light yellow solution. The reaction mixture stirred at 25° C. overnight. Solvents evaporated and residue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 30 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (40 mg, 66.4 μmol, 87.8%) as a white solid. MS (M+H)+=603; 1H NMR (CDCl3) δ: 9.19 (s, 1H), 8.45 (s, 1H), 8.36 (s, 1H), 8.07 (d, J=2.3 Hz, 1H), 7.45-7.51 (m, 1H), 7.33 (dd, J=9.1, 2.3 Hz, 1H), 6.55 (t, J=76.0 Hz, 1H), 5.74 (s, 2H), 4.22 (s, 3H), 3.95 (s, 2H), 3.68-3.78 (m, 4H), 3.55-3.66 (m, 2H), 2.11-2.28 (m, 2H), 1.89-2.07 (m, 2H), 0.88-1.04 (m, 2H), −0.02 (s, 9H).

1. customIn a 16×100 mm screw cap test tube
2. customto give a light yellow solution
3. customSolvents evaporated
4. customresidue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
5. washeluting with 0 to 5% over 30 min (MeOH containing 10% ammonium hydroxide)/dichloromethane