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 (130 mg, 202 μmol) was dissolved in THF (3 mL), and HCl 3N (672 μL, 2.02 mmol0.00) was added. After stirring the mixture at 25° C. overnight, TLC and LCMS showed about 10% conversion. Added 0.5 mL of concentrated HCl and reaction heated to 50° C. for 48 h more. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with dichloromethane (5×30 mL). The obtained organic layer was 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 30 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 (34 mg, 58.0 μmol, 28.7%). MS (M+H)+=587; 1H NMR (CDCl3) δ: 9.97 (s, 1H), 9.20 (s, 1H), 8.42 (s, 1H), 8.30 (d, J=2.3 Hz, 1H), 8.08 (s, 1H), 7.63 (d, J=9.1 Hz, 1H), 7.39 (dd, J=9.1, 2.3 Hz, 1H), 6.54 (t, J=74.4 Hz, 1H), 5.75 (s, 2H), 5.34 (s, 1H), 4.82 (t, J=6.2 Hz, 2H), 3.55-3.65 (m, 2H), 3.33 (t, J=6.4 Hz, 2H), 1.64 (s, 9H), 0.90-1.05 (m, 2H), 0.05-0.07 (m, 1H), 0.00 (s, 9H). Unreacted starting material (31 mg, 24%) as also obtained.

Provenance & Evidence