Hydrochloric Acid → HCID 86677979, compound

Participants

Reaction Conditions

Reaction Steps

2-(1-(2-(1,3-dioxan-2-yl)ethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 155 μmol) was dissolved in acetone (3 mL), and HCl 3N (1.2 g, 1 mL, 3.00 mmol9.3) was added. Heated to 50° C. with stirring and continued for 5 days. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with dichloromethane (5×30 mL). The combined organic layers were dried over anhydrous magnesium sulfate. The solvent was evaporated, and the obtained residue was purified by silica gel chromatography (n-hexane-ethyl acetate 0 to 100% over 20 min) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-oxopropyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (27 mg, 46.0 μmol, 29.7%) and a small amount of the SEM group de-protection product 2-(1-(2-(1,3-dioxan-2-yl)ethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (5 mg, 9.72 μmol, 6.27%) as light yellow needles. MS (M+H)+=515; 1H NMR (DMSO-d6) δ: 12.80 (br. s., 1H), 9.08 (s, 1H), 8.37 (s, 1H), 8.20 (d, J=2.3 Hz, 1H), 7.87 (s, 1H), 7.81 (d, J=9.1 Hz, 1H), 7.39 (dd, J=9.1, 2.3 Hz, 1H), 7.19 (t, J=74.4 Hz, 1H), 4.45-4.72 (m, 3H), 3.99 (dd, J=11.3, 4.5 Hz, 2H), 3.55-3.75 (m, 2H), 2.07-2.22 (m, 2H), 1.79-1.97 (m, 1H), 1.49 (s, 9H), 1.38 (s, 9H), 134 (m, 1H). Unreacted starting material (34 mg, 34%) was also obtained.

Provenance & Evidence