Triethylamine → 2-(4-Isopropyl-4H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carboxylic acid isoxazol-3-ylamide

Participants

Reaction Steps

To a suspension of 2-(4-isopropyl-4H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carboxylic acid (226 mg, 0.63 mmol) in DCM (5 mL) at 0° C. was added DMF (4 drops, catalytic) then oxalyl chloride (115 μL, 1.32 mmol) dropwise. The reaction mixture was stirred at room temperature for 18 hours. 3-Amino-isoxazole (233 μL, 3.15 mmol) was added followed by triethylamine (176 μL, 1.26 mmol) and the reaction mixture was stirred for 4 hours. Aqueous saturated sodium bicarbonate solution was added and then ether and the mixture was filtered. The filtrate was concentrated in vacuo to remove the organics and the resulting aqueous phase was extracted with DCM (×3). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-5% MeOH in EtOAc) then trituration with EtOAc to give 140 as an off-white solid (126 mg, 47%). LCMS: RT=9.86 min, [M+H]+=423. 1H NMR δ (ppm) (DMSO-d6): 11.39 (1 H, s), 8.94 (1 H, s), 8.81 (1 H, d, J=1.76 Hz), 8.39 (1 H, d, J=8.33 Hz), 7.79 (1 H, dd, J=8.34, 1.90 Hz), 7.70 (1 H, d, J=1.87 Hz), 7.00 (1 H, d, J=1.76 Hz), 5.51-5.41 (1 H, m), 4.41-4.35 (2 H, m), 3.47-3.41 (2 H, m), 1.54 (6 H, d, J=6.70 Hz)

Provenance & Evidence