反应详情

温度

100 °C

To a solution of 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-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 methyl ester (0.394 mmol) in MeOH (3 mL) was added 2.0M NaOH in water (1 mL). The reaction mixture was heated at 100° C. for 1 h using microwave irradiation. The crude mixture was purified by column chromatography (C18, gradient 20-60% MeOH in 0.003M HCl/H2O) then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 0.5M NH3/MeOH. The product containing fractions were combined and concentrated under reduced pressure affording 2-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-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 as a yellow solid (177 mg, 85% over two steps). LCMS: RT 2.32, 2.37, 2.44 min [M−H]− 526.8

1. custommicrowave irradiation
2. customThe crude mixture was purified by column chromatography (C18, gradient 20-60% MeOH in 0.003M HCl/H2O)
3. washwas washed with MeOH
4. washthe product eluted with 0.5M NH3/MeOH
5. additionThe product containing fractions
6. concentrationconcentrated under reduced pressure