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

温度

120 °C

A mixture of 9-bromo-2-(3-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (107 mg, 0.30 mmol), 1-isopropylpiperidine-4-thiol (72 mg, 0.45 mmol), Pd2(dba)3 (14 mg, 0.015 mmol, 5 mol %), XantPhos (17 mg, 0.030 mmol, 10 mol %) and DIPEA (210 μl, 1.20 mmol) in dioxane (4 mL) was purged with nitrogen and then heated at 120° C. for 1 h using microwave irradiation. The reaction mixture was diluted with DCM (75 mL) and purified by column chromatography (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM followed by C18, gradient 5-45% 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 9-(1-Isopropylpiperidin-4-ylsulfanyl)-2-(3-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene as a colorless gum (70 mg, 54%). LCMS: RT1.83 min [M+H]+ 435.1

1. customwas purged with nitrogen
2. custommicrowave irradiation
3. additionThe reaction mixture was diluted with DCM (75 mL)
4. custompurified by column chromatography (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM followed by C18, gradient 5-45% 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-e76d7f6203ad48c08a81aa8253c67170

出典データセット

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09090628B2