Cesium carbonate → 2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-9-(piperidin-4-ylsulfanyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 2 (0.244 g, 0.594 mmol), 2-bromo-2-methylpropionamide (0.494 g, 2.976 mmol) and Cs2CO3 (0.774 g, 2.376 mmol) in CH3CN (15 mL) was heated at 120° C. for 2 h using microwave irradiation. The crude mixture was filtered through a pad of Celite® and the filtrate was concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM) to give 0.261 g (89% yield) of 2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide as a colorless foam. A portion of the resulting residue (28 mg) was further purified by column chromatography (C18, gradient 15-55% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 0.5M NH3/MeOH affording the title compound (13 mg). LCMS: RT 2.92 min [M+H]+ 496.1.

Provenance & Evidence