Water → N-[4-amino-5-cyano-6-(2-hydroxyethoxy)pyridin-2-yl]-2-(2,5-dimethoxyphenyl)acetamide

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Reaction Steps

To a solution of 39 mg (0.20 mmol) of 4,6-diamino-2-(2-hydroxy-ethoxy)-nicotinonitrile in 0.2 mL of pyridine and 1 mL of CH2Cl2 was added 75 mg (0.39 mmol) of 2,5-dimethoxyphenylacetyl chloride (Example 60B). The mixture was stirred at ambient temperature for 1 hours then 1 mL of water was added, and the solvents were removed under reduced pressure. The residue was taken up in 10 mL of ethyl acetate, then extracted with 1M HCl(aq.) (2×5 mL), saturated NaHCO3(aq.) (2×5 mL), and brine (1×5 mL), dried over MgSO4, filtered, and concentrated to an oil. This was dissolved in 1:1 DMSO:methanol and purified by reversed phase HPLC, eluting with a 5-100% CH3CN gradient in 0.01M NH4OAc(aq.) to provide a white solid. This was dissolved in 1 mL of THF, and 1 mL of 2M NaOH(aq.) was added. The solution was stirred at ambient temperature for 18 hours then concentrated under reduced pressure. The residue was taken up in 10 mL of ethyl acetate, then extracted with water (1×3 mL), 2M NaOH(aq.) (1×3 mL), and brine (1×3 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to a white solid. This was recrystallized from 1 mL of methanol to provide 4 mg (5%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.10 (s, 11H), 7.13 (s, 1H), 6.90 (m, 3H), 6.79 (m, 2H), 4.81 (t, 1H, J=5.4 Hz), 4.31 (m, 2H), 3.69 (m, 8H), 3.66 (s, 2H); MS (ESI) m/e=329 (M−EtOH+H)+, 373 (M+H)+, 371 (M−H)−.

Provenance & Evidence