Benzoylhydrazine → 7-(5-phenyl-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine

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Reaction Steps

To a solution of 1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carbonyl chloride (40 mg, 0.118 mmol; Example 1 Step 1) in DCM (1.5 mL) was added benzohydrazide (32.2 mg, 0.236 mmol) and DIPEA (50 μL, 0.286 mmol). The reaction was stirred at room temperature for 16 hours. TLC analysis of the reaction mixture indicated consumption of starting material. The reaction was quenched with saturated aqueous NaHCO3 (2 mL) and was extracted with DCM (3×2 mL). The combined organics were dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting solid was dissolved in DMF (3 mL) and treated with Burgess reagent (28.1 mg, 0.118 mmol). The reaction mixture was heated to 180° C. by heating under microwave irradiation for 5 minutes. The mixture was concentrated in vacuo. The resulting paste was purified by flash column chromatography using a gradient elution of hexanes with 10-90% EtOAc. The resulting tan solid was triturated with water (2×10 mL) to provide 7-(5-phenyl-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine (4.6 mg, 10.39 μmol, 8.80% yield) as a white solid. LCMS (+ESI) m/z=421.0 [M+H]+; 1H-NMR (CDCl3) δ 8.90 (d, 1H), 8.84 (d, 1H), 8.17 (m, 2H), 7.74 (m, 2H), 7.65 (tt, 1H), 7.59-7.51 (m, 5H), 4.02 (m, 2H), 3.95 (m, 2H).

Provenance & Evidence