反应详情

温度

50 °C

A solution of 4-(benzyloxy)-1-(1-(2-chloroethyl)-1H-indazol-5-yl)pyridin-2(1H)-one (174 mg, 0.458 mmol) in DMF (2 mL) was treated with piperazine (788 mg, 9.15 mmol), Cs2CO3 (746 mg, 2.29 mmol) and KI (38 mg, 0.23 mmol). After stirring at 50° C. for 16 h, the reaction mixture was diluted with H2O (25 mL) and extracted with EtOAc (3×25 mL). The organics were washed with brine (25 mL), dried (Na2SO4), filtered and concentrated. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH/NH4OH, 30:1:0.1 to 20:1:0.2) provided the free base. This was dissolved in ethyl acetate (0.5 mL) and treated with 1 equivalent of 1 M HCl in Et2O. The resulting mixture was filtered to provide the title compound (157 mg, 74%) as a yellow solid: melting point (mp) 217-218° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.17 (s, 1H), 7.81 (d, J=8.8 Hz, 1H), 7.75 (s, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.49-7.41 (m, 4H), 7.40-7.35 (m, 2H), 6.13-6.10 (m, 1H), δ 99 (d, J=2.7 Hz, 1H), 5.15 (s, 2H), 4.79-4.51 (m, 2H), 3.51-3.35 (m, 6H), 3.22-2.98 (m, 4H); ESI MS m/z 430 [M+H]+.

1. extractionextracted with EtOAc (3×25 mL)
2. washThe organics were washed with brine (25 mL)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH/NH4OH, 30:1:0.1 to 20:1:0.2)
7. customprovided the free base
8. filtrationThe resulting mixture was filtered