反应详情

Into a one dram vial, 2-(4-{4-[7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidin-1-yl)-acetamide (89 mg, 0.12 mmol), Methylene chloride (1.50 mL), and Trifluoroacetic Acid (0.50 mL, 6.5 mmol) was added. The reaction mixture was stirred at room temperature for 2 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 lyophilized to give a yellow solid. The TFA salt was neutralized via a polymer sulfonic acid bound resin and washed with 2M NH3 in methanol. The solvent was removed to afford a yellow solid. The solid was triturated with Et2O to give 2-[4-(4-{5-Hydroxy-7-[2-(methanesulfonyl-methyl-amino)-phenyl]-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidin-1-yl]-acetamide as a yellow solid (28 mg, 32%). LCMS (E/I+) 580.15 (M+H). NMR 1H (DMSO-d6)-9.94 (s, 1H), 8.74 (s, 1H), 7.94-8.02 (m 1H), 7.88 (d, 1H, J=8.25 Hz), 7.59-7.67 (m, 1H), 7.48-7.56 (m, 2H), 7.40 (s, 1H), 7.21 (bs, 1H), 7.13 (bs, 1H), 6.85 (s, 1H), 6.67 (d, 1H, J=8.31 Hz), 6.35 (s, 1H), 3.83 (s, 3H), 3.05 (s, 3H), 2.77-2.99 (m, 7H), 2.32-2.45 (m, 1H), 2.06-2.23 (m, 2H), 1.60-1.87 (m, 4H).

1. customThe solvent was removed under vacuum
2. customThe reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN
3. customto give a yellow solid
4. washwashed with 2M NH3 in methanol
5. customThe solvent was removed
6. customto afford a yellow solid
7. customThe solid was triturated with Et2O