반응 #1861045

ord-aad906bc4e4f47fca7e89e9a891b10a9

반응 조건

온도
120°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도the reaction mixture is heated to 120° C. for 3 hours
  2. 2
    추출The aqueous phase is extracted three times with CH2Cl2
  3. 3
    건조The organic phase is dried over magnesium sulphate
  4. 4
    여과filtered
  5. 5
    기타the solvent is removed under reduced pressure
  6. 6
    기타The residue is pre-purified by silica gel chromatography
  7. 7
    세척eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1)

실험 절차

To a solution of compound 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (50 mg, 0.12 mmoles) in 1,4-dioxane (500 μL) in a screw-capped vial under argon are added potassium vinyltrifluoroborate (21 mg, 0.156 mmole), Pd(OAc)2 (1.35 mg, 6 μmole), RuPhos (3 mg, 6 μmole), K2CO3 (50 mg, 0.36 mmole) and water (400 μL). The reaction mixture is heated to 120° C. for overnight. As the reaction is not complete, potassium vinyltrifluoroborate (21 mg, 0.156 mmole), Pd(OAc)2(1.35 mg, 6 μmole), RuPhos (3 mg, 6 μmole) are added and the reaction mixture is heated to 120° C. for 3 hours. Water is added, pH adjusted to 9-10 with saturated Na2CO3 solution. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (99:1:0.1) to (95:5:0.5) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford 4-(1-methylpiperidin-4-yloxy)-2-vinyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US09255101B2uspto-grants-2016_02