Sulfamic Acid → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (217 mg, 458 μmol) in dioxane (6.5 mL) and water (2 mL) at 0° C. was added sulfamic acid (267 mg, 2.75 mmol), followed by drop-wise addition of a solution of sodium chlorite (67.3 mg, 596 μmol) and KH2PO4 (748 mg, 5.5 mmol) 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. THF (6.5 mL) added to the yellow suspension and reaction continued at 25° C. for 2 h, then sulfamic acid (267 mg, 2.75 mmol) was added followed by dropwise addition of sodium chlorite (67.3 mg, 596 μmol) and KH2PO4 (748 mg, 5.5 mmol) in 5 mL of water. After 2 h the mixture was diluted with water (20 mL) and extracted with dichloromethane (3×30 mL). The combined organic layers were dried (MgSO4) and evaporated. The light yellow solid residue was dissolved in dichloromethane/MeOH and dichloromethane evaporated to promote solid formation, the solid separated by filtration, rinsed with MeOH and hexanes then dried to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (127 mg, 259 μmol, 57%) as a light yellow solid. MS (M+H)+=490; 1H NMR (DMSO-d6) δ: 12.57 (br. s., 1H), 9.12 (s, 1H), 8.69 (s, 1H), 8.65 (d, J=2.3 Hz, 1H), 7.80 (d, J=9.1 Hz, 1H), 7.35 (dd, J=8.9, 2.5 Hz, 1H), 7.20 (t, J=74.8 Hz, 1H), 5.71 (s, 2H), 4.18 (s, 3H), 3.58 (t, J=7.9 Hz, 2H), 0.84 (t, J=7.9 Hz, 2H), −0.21-−0.01 (s, 9H).

Provenance & Evidence