Water → 3-(7-carboxy-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide

Participants

Reaction Conditions

Reaction Steps

To a yellow-brown solution of 2-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (265 mg, 644 μmol) in dioxane (14.0 mL) and water (4 mL) at 0° C. (became a suspension after cooling) was added sulfamic acid (375 mg, 3.86 mmol, Eq: 6.00), followed by drop-wise addition of a solution of sodium chlorite (94.6 mg, 837 μmol.30) and KH2PO4 (1.05 g, 7.73 mmol2.00) in water (4.5 mL) via dropping funnel over 15 min. The ice bath was removed and the light yellow suspension was stirred at 25° C. for 18 h. Mixture diluted with water (50 mL) and extracted with 5% MeOH in dichloromethane (3×40 mL). The combined organic layers were dried (MgSO4) and evaporated. Light yellow solid residue was dissolved in dichloromethane and purified by chromatography (spherical silica 20-45 μm, 50 g, Versaflash Supelco) eluting with 0 to 5% MeOH in dichloromethane. Pure compound dissolved in dichloromethane, added some cyclohexane and dichloromethane evaporated to promote solid formation, solid separated by filtration, rinsed with hexanes and dried to give 3-(7-carboxy-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (147 mg, 331 μmol, 51.5%) as a white solid. MS (M+H)+=444 (100% purity); 1H NMR (CDCl3) δ: 9.19 (s, 1H), 8.45 (s, 1H), 5.76 (s, 2H), 3.58-3.71 (m, 2H), 3.50 (s, 3H), 2.39-2.55 (m, 2H), 2.24-2.38 (m, 2H), 1.99-2.22 (m, 4H), 0.91-1.07 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence