Potassium Carbonate → HCID 89761699, compound

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with INTERMEDIATE D (0.100 g, 0.192 mmol), (N-tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (Maybridge Chemicals, Cornwall, UK, 0.059 mL, 0.192 mmol), tetrakis(triphenylphosphine)palladium(0) (0.022 g, 0.019 mmol), and K2CO3 (0.133 g, 0.959 mmol). The solids were diluted with dioxane (1.279 mL) and water (0.639 mL), and the reaction was heated under microwave irradiation at 100° C. for 10 minutes (starting material remained, but moved forward). The reaction mixture was diluted with water, and washed with DCM. Equal partitioning between both layers was observed (and an emulsion formed), so the organic and aqueous were combined and concentrated until just the water remained. The aqueous was washed with DCM (×3) and the organics were then combined and dried using a phase separator. After concentration, the material was purified by reverse-phase preparative HPLC (Column: Phenomenex 150×30 mm, 5 micron, C18 column; 0.1% TFA in CH3CN/H2O, gradient 25% to 90% over 20 min) to provide tert-butyl 4-(2-(7-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2 H)-carboxylate (0.035 g, 0.056 mmol) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.37 (s, 9 H) 2.16-2.37 (m, 2 H) 3.51-3.72 (m, 4 H) 3.81-3.90 (m, 2 H) 4.22-4.34 (m, 2 H) 5.84 (br. s., 1 H) 6.38-6.46 (m, 1 H) 7.10-7.17 (m, 2 H) 7.56 (d, J=8.31 Hz, 1 H) 7.65 (d, J=2.05 Hz, 1 H) 7.72 (dd, J=8.41, 2.15 Hz, 1 H) 8.42 (s, 1 H). m/z (ESI) 524.0 (Boc group falls off in LCMS).

Provenance & Evidence