Sodium Methoxide → HCID 178521001, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-3-(1-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-ylcarbamoyl)cyclopropyl)pyridine 1-oxide (0.25 g, 0.55 mmol) in isobutanol (5 mL) was added a solution of sodium methoxide (0.15 g, 2.77 mmol) in methanol (2 mL) at room temperature. The reaction mixture was heated to 110° C. for 16 h. The mixture was then cooled to room temperature, diluted with ethyl acetate, and washed with water. The organic layer was dried, filtered, and concentrated under reduced pressure. The resulting residue was purified first via flash chromatography (100-200 mesh silica gel, 0-10% methanol in dichloromethane) then via preparative HPLC to obtain the product which was further purified by chiral separation to afford (R)-3-(1-(5-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)cyclopropyl)pyridine 1-oxide (70 mg). Chiral HPLC retention time: 13.808 min (Method: CHIRAL PAK IA, 4.6×250 mm 5 μm column, Mobile Phase: A: 0.1% DEA in n-hexane, Mobile Phase B: ethanol; isocratic; 70:30, 1 mL/min, Temperature 25 C) min MS (ES+APCI) (M+H) 433.1; LCMS retention time 4.698 min (Method B1). 1H NMR (400 MHz, CD3OD) δ 1.52-1.57 (m, 2H), 1.59-1.69 (m, 1H), 1.71-1.84 (m, 4H), 1.86-2.08 (m, 5H), 2.75 (t, 2H), 2.88-3.00 (m, 2H), 3.43 (t, 2H), 3.47-3.57 (m, 1H), 3.68 (br s, 1H), 4.27 (d, 1H), 4.52 (d, 1H), 6.78 (d, 1H), 7.50-7.56 (m, 1H), 7.58-7.72 (m, 2H), 8.26 (d, 1H), 8.31 (br s, 1H).

Provenance & Evidence