Tetrahydrofuran → 5-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoxaline

Participants

Reaction Steps

Add THF (2.2 mL) to trifluoro-methanesulfonic acid quinoxalin-5-yl ester (292 mg, 1.05 mmol) and purge the solution with nitrogen for 10 min. Add tris(dibenzylideneacetone)dipalladium(0) (80 mg, 0.087 mmol) and bis(1,2-bis(diphenylphosphino)ethane)palladium(0) (78 mg, 0.087 mmol), purge the reaction with nitrogen for 2 min, and stir the reaction at room temperture for 20 min. Add 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 200 mg, 0.87 mmol) in 1:1 DMF/THF (2 mL) and stir for 10 min. Add 2.0M aqueous potassium carbonate (1.04 mL, 2.1 mmol) and heat the reaction to 65° C. Add additional tris(dibenzylideneacetone)dipalladium(0) (80 mg, 0.087 mmol) after 1 h and 3 h. Stir the reaction at 65° C. for 18 h, filter through Celite® with methanol/chloroform, and concentrate in vacuo. Purify by flash column chromatography followed by reverse-phase preparative HPLC. Concentrate the pure fractions from the preparative HPLC in vacuo, take up in methanol, treat with MP-carbonate beads, filter, and concentrate in vacuo to provide the title compound (11 mg, 7%) as a clear, colorless oil. MS APCI+ m/e 314 (M+1). 1H NMR (DMSO-d6) δ 8.78 (m, 1H), 8.68 (m, 1H), 8.54 (m, 1H), 8.08 (m, 1H), 7.72 (m, 3H), 7.53 (m, 1H), 7.22 (m, 1H), 4.37 (m, 2H), 2.95 (m, 2H), 2.64 (m, 2H). HPLC: 98.6%, Rt=13.5 min. TLC (SiO2): Rf0.2 (1:3 [80:18:2 chloroform/methanol/concentrated aqueous ammonium hydroxide]/dichloromethane).

Provenance & Evidence