反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
实验步骤: Into an 8-dram vial, Trifluoro-methanesulfonic acid 7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (88.0 mg, 0.195 mmol), 2-Methoxy-4-morpholin-4-ylmethyl-phenylamine (0.174 g, 0.782 mmol), N,N-Diisopropylethylamine (0.136 mL, 0.782 mmol), and 1-Methoxy-2-propanol (0.880 mL, 9.00 mmol) were added. The reaction mixture was heated at 120° C. for 4 hours. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were concentrated under vacuum to give a glassy solid. The solid was triturated with Et2O to give N-{2-[2-(2-Methoxy-4-morpholin-4-ylmethyl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-N-methyl-methanesulfonamide as a yellow solid (46 mg, 37%). LCMS (E/I+) 523.15 (M+H). NMR 1H (DMSO-d6)-9.61 (s, 1H), 8.13 (d, 1H, J=8.58 Hz), 7.95-8.00 (m, 1H), 7.86 (s, 1H), 7.66-7.70 (m, 1H), 7.53-7.58 (m, 1H), 7.16 (d, 1H, J=1.72 Hz), 7.04 (d, 1H, J=4.66 Hz), 7.01 (d, 1H, J=4.66 Hz), 6.96 (d, 1H, J=8.58 Hz), 4.29 (d, 2H, J=3.50 Hz), 3.86-4.04 (m, 5H), 3.61 (t, 2H, J=11.67 Hz), 3.20 (d, 2H, J=12.84 Hz), 3.00-3.15 (m, 5H), 2.88 (s, 3H).
The solvent was removed under vacuum
The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN
The collected fractions were concentrated under vacuum
to give a glassy solid
The solid was triturated with Et2O
来源 ID: ord-3a25083238bb455b86d6d7675efadde6