反应详情

温度

75 °C

To a solution of 2-(methylsulfanyl)ethyl 2-aminoacetate HCl salt (792 mg, 3.57 mmol) in CH3CN was added N-[1-(2-bromoethyl)-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (364 mg, 0.71 mmol) and DIEA (1.57 g, 12.15 mmol). The resulting solution was stirred at 75° C. overnight and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (2#-Waters 2767-2 (HPLC-08)): Column, Xbridge Prep Phenyl, 5 um, 19×150 mm; mobile phase, Water with 50 mmol ammonium bicarbonate and acetonitrile (10.0% acetonitrile up to 33.0% in 2 min, up to 53.0% in 8 min, up to 100.0% in 1 min, down to 10.0% in 1 min); Detector, UV 220 nm. This resulted in 53.1 mg (2%) of the formic acid salt of 2-(methylsulfanyl)ethyl 2-[(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]ethyl)amino]acetate as light yellow oil. LCMS (Method 20): [M+H]+=580.15, RT=2.76 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.73 (s, 1H), 9.33 (dd, 1H, J=1.5, 6.9 Hz), 8.67 (dd, 1H, J=1.5, 4.2 Hz), 8.66 (s, 1H), 8.36 (s, 1H), 7.65-7.61 (m, 2H), 7.44 (d, 1H, J=9.3 Hz), 7.23 (dd, 1H, J=4.5, 7.2 Hz), 6.99 (t, 1H, J=73.5 Hz), 4.27-4.18 (m, 4H), 3.38 (s, 2H), 2.99 (t, 2H, J=6.0 Hz), 2.67 (t, 2H, J=6.6 Hz), 2.07 (s, 3H).

1. concentrationconcentrated under vacuum
2. customThe crude product was purified by Prep-HPLC with the following conditions (2#-Waters 2767-2 (HPLC-08))
3. waitup to 53.0% in 8 min
4. waitup to 100.0% in 1 min
5. waitdown to 10.0% in 1 min)