[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[C:15]3[C:11]([C:12]([NH2:17])=[N:13][NH:14]3)=[CH:10][CH:9]=2)[CH:5]=[C:4](SC)[N:3]=1.OO.O1CCOCC1.[NH:28]1[CH2:33][CH2:32][S:31][CH2:30][CH2:29]1>FC(F)(F)C(O)=O.CCOC(C)=O>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[C:15]3[C:11]([C:12]([NH2:17])=[N:13][NH:14]3)=[CH:10][CH:9]=2)[CH:5]=[C:4]([N:28]2[CH2:33][CH2:32][S:31][CH2:30][CH2:29]2)[N:3]=1To 6-[2-amino-6-(methylthio)-4-pyrimidinyl]-1H-indazol-3-amine (0.43 g, 1.58 mmol) in trifluoroacetic acid (TFA) (15 mL) at 0° C. was added aqueous H2O2 (0.97 mL, 9.47 mmol, 30% (w/w)) dropwise. After 10 minutes, the reaction mixture was allowed to warm to room temperature and stirred at this temperature for 30 minutes. LCMS showed a mixture of sulfoxide and sulfone. The reaction mixture was cooled to 0° C. and quenched with dimethyl sulfide (1.0 mL, 13.5 mmol, dropwise addition) to ensure no hydrogen peroxide is left. The reaction mixture was warmed to room temperature and diluted with diethyl ether (Et2O). When the oxidation converts all the starting material to the sulfone, this material precipitate out when Et2O is added. However, this time the sulfoxide species was the dominant (˜80%) as shown in the LCMS. Therefore, hexane was added to ensure complete precipitation of the sulfoxide and sulfone mixture. The material was filtered, and the solid was treated with 1,4-dioxane (10 mL) and thiomorpholine (1.21 mL, 12.6 mmol). The reaction mixture was stirred overnight at 100° C. The mixture was cooled to room temperature and poured onto water and EtOAc. The layers were separated and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. The crude mixture was purified via flash chromatography on SiO2 (gradient: 99:1:0.1 CHCl3/CH3OH/NH4OH to 90:10:1 CHCl3/CH3OH/NH4OH). The fractions containing the desired product were combined and concentrated. Trituration with Et2O afforded the title compound (205 mg, 40%) as a yellow solid. LC-MS (ES) m/z=328 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 2.61 (m, 4H), 3.99 (m, 4H), 5.37 (s, 2H), 6.12 (s, 2H), 6.61 (s, 1H), 7.58 (dd, J=8.6, 1.3 Hz, 1H), 7.70 (d, J=8.6 Hz, 1H), 7.95 (s, 1H), 11.50 (s, 1H).
불러오는 중…
