反应详情

To a solution 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 methyl ester (50 mg, 0.0979 mmol) in THF (4 mL) was added 1.0M LiOH in water (0.5 mL). The reaction mixture was first stirred at RT for 6 h, then left at RT for 7 days, and then heated at 120° C. for 1 h using microwave irradiation. Volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (C18, gradient 2-80% MeOH in H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH affording the title compound as a white solid (20 mg, 42%). LCMS: RT 2.45 min [M−H]+ 495.0.

1. waitleft at RT for 7 days
2. temperatureheated at 120° C. for 1 h
3. custommicrowave irradiation
4. customVolatiles were removed under reduced pressure
5. customthe resulting residue was purified by column chromatography (C18, gradient 2-80% MeOH in H2O)
6. washThe cartridge was washed with MeOH
7. washthe product eluted with 2M NH3/MeOH affording the title compound as a white solid (20 mg, 42%)