Acetic Acid → {2-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone

Participants

Reaction Steps

25.0 mg (0.046 mmol) of 2-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoic acid was combined with 18.5 mg (0.114 mmol) of N,N′-carbonyldiimidazole in 1.0 mL dimethylformamide. The solution was stirred at room temperature for 2 hours whereupon 9.9 μL (0.114 mmol) of morpholine was added and the solution was stirred at room temperature for 16 hours. The crude reaction mixture was then diluted with 1.0 mL methanol and 100 μL of 50% w/v potassium hydroxide aqueous solution was added. The mixture was stirred at room temperature for 2 hours and then neutralized with acetic acid. The material was filtered through a 0.45 μm syringe filter and purified by mass-triggered reverse phase HPLC in a gradient of acetonitrile and water (containing 0.1% formic acid). The clean fractions were lyophilized to afford 6.9 mg (0.015 mmol, 32% yield) of {2-amino-3-chloro-5-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone as a fluffy white powder. 1H NMR (500 MHz, MeOD) δ 8.39 (d, 1H), 8.15 (d, 1H), 7.65 (s, 1H), 7.64 (d, 1H), 7.58 (dd, 1H), 7.36 (d, 1H), 7.31 (t, 1H), 7.13 (d, 1H), 7.06 (t, 1H), 3.86 (s, 3H), 3.72 (s, br., 8H); MS: m/z 463.0 (M+H+).

Provenance & Evidence