反应详情

A solution of 3,5-bis(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (74 mg, 0.17 mmol) and HCl (5-6 M in IPA, 3.4 mL, 16.9 mmol) in 5 mL of MeOH was heated at 80° C. for 90 min. The crude reaction was cooled to RT and concentrated to a yellow solid that was slurried with a 1\1 mixture of DCM\MeOH (12 mL) and applied to a pre-washed (45 mL MeOH) of Si-propylsulfonic acid (12 g, Silicycle, Cat# R51230B). The column was washed with MeOH (35 mL). The compound was released with 35 mL of 2 M NH3 in MeOH. The crude product was purified by silica gel chromatography, eluting with a gradient of 0-75% EtOAc in hexanes, to provide the title compound (20 mg, 0.056 mmol, 33% yield) as a white solid. MS (ESI, pos. ion) m/z: 355.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.09-9.16 (m, 2H), 8.97 (s, 1H), 8.60 (d, J=16.63 Hz, 2H), 8.15 (dt, J=8.80, 0.88 Hz, 1H), 7.74 (d, J=8.80 Hz, 1H), 2.32-2.38 (m, 1H), 2.25-2.31 (m, 1H), 1.16-1.26 (m, 6H), 1.09-1.15 (m, 2H).

1. customThe crude reaction
2. concentrationconcentrated to a yellow solid
3. additionthat was slurried with a 1\1 mixture of DCM\MeOH (12 mL)
4. washa pre-washed (45 mL MeOH) of Si-propylsulfonic acid (12 g, Silicycle, Cat# R51230B)
5. washThe column was washed with MeOH (35 mL)
6. customThe crude product was purified by silica gel chromatography
7. washeluting with a gradient of 0-75% EtOAc in hexanes