反应详情

To a stirred solution of 1-cyclopropyl-3-(2-fluoro-4-iodo-phenylamino)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (2-vinyloxy-ethoxy)-amide (57.0 mg, 0.109 mmol) in anhydrous MeOH (5.5 mL) and anhydrous THF (2.7 mL) under N2 was added 4 M HCl in dioxane (817 μL, 0.327 mmol, 3.0 eq), and the reaction mixture was stirred at room temperature. After 1 h the solvent was removed in vacuo and the residue was redissolved in acetonitrile (2.0 mL) and loaded onto Phenomenex Strata-X cartridge (5 g). The cartridge was washed with water (10 mL) and methanol (15 ml). The desired product was then eluted using 2M ammonia in MeOH. Trituration from DCM-hexane afforded the title compound as a tan solid (32.9 mg, 60.8%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.54 (s, 1H), 8.32 (d, J=5.9 Hz, 1H), 7.70-7.41 (m, 3H), 7.20 (dd, J=8.50 Hz, 1H), 6.26 (t, J=9.6 Hz, 1H), 4.78 (br s, 1H), 3.87 (dd, J=6.31 Hz, 2H), 3.70-3.39 (m, 3H), 1.27 (br s, 1H), 1.18-1.03 (m, 2H), 0.90-0.67 (m, 2H); LC-MS (method C): [M+H]+=497.0, RT=0.57 min.

1. customAfter 1 h the solvent was removed in vacuo
2. dissolutionthe residue was redissolved in acetonitrile (2.0 mL)
3. washThe cartridge was washed with water (10 mL) and methanol (15 ml)
4. washThe desired product was then eluted