反应详情

To a suspension 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}-2-methylpropionic acid (20 mg, 0.0411 mmol) in DMF (1.5 mL) was added DIPEA (21 ul, 0.123 mmol), HOBt.NH3 (9 mg, 0.0616 mmol) and EDCI (12 mg, 0.0616 mmol) and the reaction mixture was stirred at RT for 18 h. The mixture was then partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc and the combined organic layers were washed with water, followed by brine, then dried and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM) affording 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 gum (16 mg, 77%). LCMS: RT 2.16/2.19 min [M+H]+ 496.1

1. customThe mixture was then partitioned between EtOAc and water
2. extractionThe aqueous layer was further extracted with EtOAc
3. washthe combined organic layers were washed with water
4. customdried
5. concentrationconcentrated in vacuo
6. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% 2M NH3/MeOH in DCM)