反应详情

温度

60 °C

A stirred mixture of N-(4-(1-(4-methoxybenzyl)-3-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (2 mg, 0.002767 mmol), and 2,2,2-trifluoroacetic acid (0.2132 ml, 2.767 mmol) was heated to 60° C. in a sealed vessel for 18 hours. After cooling to ambient temperature, the reaction was concentrated in vacuo, using toluene to azeotrope residual TFA. The resulting residue was dissolved in DCM, and purified by preparative TLC (0.5 mm thickness, Rf=0.50), eluting with 10% MeOH (containing 7N NH3) in DCM. The product was obtained as a pale yellow powder (1 mg, 48%). HPLC: 89% purity (220 nm); LRMS (APCI+): 100% purity, 220 nm, m/z 603 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 11.87 (s, 1H), 9.81 (s, 1H), 8.44 (m, 1H), 8.26 (m, 2H), 7.98 (m, 1H), 7.63 (m, 2H), 7.42 (m, 1H), 7.28 (m, 3H), 6.22 (m, 1H), 3.75 (m, 1H), 3.61 (m, 3H), 3.39 (s, 3H), 2.73 (m, 4H), 1.5-2.2 (m, 4H).

1. temperatureAfter cooling to ambient temperature
2. concentrationthe reaction was concentrated in vacuo
3. dissolutionThe resulting residue was dissolved in DCM
4. custompurified by preparative TLC (0.5 mm thickness, Rf=0.50)
5. washeluting with 10% MeOH (containing 7N NH3) in DCM