反应详情

温度

120 °C

A mixture of 9-bromo-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (210 mg, 0.541 mmol), 1-isopropylpiperidine-4-thiol (129 mg, 0.812 mmol), Pd2(dba)3 (25 mg, 5 mol %), XantPhos (31 mg, 10 mol %) and DIPEA (380 μl, 2.16 mmol) in dioxane (5 mL) was purged with nitrogen and then heated at 120° C. for 1 h using microwave irradiation. The reaction mixture was then diluted with DCM (75 mL) and purified by column chromatography (Si-PCC, gradient 2-15% MeOH in DCM followed by C18, gradient 15-50% MeOH in 0.5% TFA/H2O). The product containing fractions were combined and concentrated in vacuo. The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 0.5M NH3/MeOH. The basic fractions were concentrated under reduced pressure affording 2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-9-(1-isopropylpiperidin-4-ylsulfanyl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene as a white solid/gum (146 mg, 58%). LCMS: RT 2.20 min [M+H]+ 467.0

1. customwas purged with nitrogen
2. custommicrowave irradiation
3. additionThe reaction mixture was then diluted with DCM (75 mL)
4. custompurified by column chromatography (Si-PCC, gradient 2-15% MeOH in DCM followed by C18, gradient 15-50% MeOH in 0.5% TFA/H2O)
5. additionThe product containing fractions
6. concentrationconcentrated in vacuo
7. washwas washed with MeOH
8. washthe product eluted with 0.5M NH3/MeOH
9. concentrationThe basic fractions were concentrated under reduced pressure