Diisopropylethylamine → 9-(1-Isopropylpiperidin-4-ylsulfanyl)-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene

温度

120 °C

A mixture of 9-bromo-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (147 mg, 0.411 mmol), 1-isopropylpiperidine-4-thiol (98 mg, 0.617 mmol), Pd2(dba)3 (19 mg, 5 mol %), XantPhos (24 mg, 10 mol %) and DIPEA (288 l, 1.64 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 (100 mL) and purified by column chromatography (Si-PCC, gradient 0-8% 2M NH3/MeOH in DCM followed by C18, gradient 10-50% MeOH in 0.5% TFA/H2O). The product containing fractions were combined and concentrated in vacuo and 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 the title compound as a colorless foam (138 mg, 77%). LCMS: RT1.79 min [M+H]+ 435.2

1. customwas purged with nitrogen
2. custommicrowave irradiation
3. additionThe reaction mixture was then diluted with DCM (100 mL)
4. custompurified by column chromatography (Si-PCC, gradient 0-8% 2M NH3/MeOH in DCM followed by C18, gradient 10-50% 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

ORDレコード

ord-9c1293ec0449488f8e6cb9a83f647585

出典データセット

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09090628B2