Water → Methyl (4-{3-cyano-4-(1,2-dihydroxyethyl)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate

Participants

Reaction Steps

To the suspension of methyl (4-{3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-4-vinyl-2-thienyl}pyridin-2-yl)carbamate (0.625 g, 1.34 mmol) in tert-butyl alcohol (3.0 mL) and acetone (30 mL) was added N-methylmorpholine N-oxide (0.315 g, 2.69 mmol), followed by water (1.0 mL) then 0.157 M of osmium tetraoxide in Water (0.257 mL, 0.0404 mmol). The pale yellow suspension was stirred at room temperature for 17 hours. N-Methylmorpholine N-oxide (0.315 g, 2.69 mmol) was added and the suspension was stirred for 3 more hours, then heated to reflux for 7 hours. The mixture was cooled to room temperature, rotavaped and azeotroped with MeOH to give a solid crude residue. The crude solid was partially dissolved in DCM-MeOH, coated on silica gel, evaporated in rotavapor and chromatographed in a silica gel column using an elution of MeOH/DCM (0/100 to 5/95) to afford a solid product (0.365 g, yield 57.6%). LC/MS: (FA) ES+ 471; ES− 469. 1H NMR (400 MHz, d-chloroform/d4-methanol) δ 8.35 (m, 2H), 8.30 (m, 1H), 7.40 (m, 1H), 5.47-5.49 (m, 1H), 5.31-5.33 (m, 1H), 4.03-4.07 (m, 1H), 3.87 (m, 1H), 3.79 (s, 3H), 3.71-3.81 (m, 2H), 2.13 (m, 1H), 2.00-2.02 (m, 2H), 1.65-1.70 (m, 3H).

Provenance & Evidence