反应详情

温度

100 °C

2-Amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid 5a (100 mg, 0.4063 mmol), 4-methoxypyridin-3-amine (50.44 mg, 0.4063 mmol) and DIPEA (52.51 mg, 70.77 μL, 0.4063 mmol) were dissolved in dry NMP (812.6 μL) in a microwave tube. TBTU (130.5 mg, 0.4063 mmol) was added in one portion and the resulting mixture was stirred at RT for ˜10 minutes and at 100° C. for ˜2 h under microwave conditions. The reaction mixture was allowed to cool to RT and filtered through a SCX-2 cartridge (5 g). The cartridge was washed with MeOH/DCM and eluted with 2M NH3 in MeOH (3×10 mL). The eluate was concentrated under reduced pressure. The residue was purified by column chromatography on silica (7.5% MeOH in DCM, ˜75 mL) to give the desired Compound I-O-1 as a bright yellow solid (87.9 mg, 61% Yield). LC-MS (M+H)+353.1; 1H NMR (500 MHz, DMSO-d6) δ 9.93 (s, 1H), 9.55 (s, 1H), 9.26 (dd, 1H), 8.24 (dd, 1H), 7.50-7.51 (d, 1H), 7.17-7.18 (d, 1H), 6.99 (s, 2H), 4.00 (s, 3H).

1. temperatureto cool to RT
2. filtrationfiltered through a SCX-2 cartridge (5 g)
3. washThe cartridge was washed with MeOH/DCM
4. washeluted with 2M NH3 in MeOH (3×10 mL)
5. concentrationThe eluate was concentrated under reduced pressure
6. customThe residue was purified by column chromatography on silica (7.5% MeOH in DCM, ˜75 mL)