반응 #45120

ord-fc3dbbd8a23444f3b8066829388d5400

반응 조건

온도
65°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    여과the mixture was filtered through celite
  2. 2
    기타The filtrate was transferred to a separating funnel
  3. 3
    기타the aqueous layer removed
  4. 4
    세척The ethyl acetate layer was washed with saturated brine
  5. 5
    건조dried over magnesium sulphate
  6. 6
    여과After filtration the solvent
  7. 7
    기타was evaporated
  8. 8
    기타to give the crude product as a yellow gum
  9. 9
    기타The crude product was purified by preparative LCMS
  10. 10
    workup.ADDITIONFractions containing the desired compound
  11. 11
    기타were evaporated to dryness

실험 절차

2M Trimethylaluminium (1.250 ml, 2.50 mmol) in toluene, was added dropwise to a stirred solution of ethyl 5-(3,3-dimethylpiperazin-1-yl)thiophene-2-carboxylate (0.268 g, 1 mmol) and 5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine hydrochloride (0.286 g, 1.00 mmol) in toluene (7.14 ml) at 65° C. under nitrogen. The reaction mixture was stirred and heated at 65° C. for 4 h then 50° C. for 18 h followed by 80° C. for 5 h. Ethyl acetate (5 mL) was added to the reaction mixture followed by a solution of potassium sodium tartrate (5 mL, 20% aqueous). More ethyl acetate (50 mL) and water (25 mL) was added and the mixture was filtered through celite. The filtrate was transferred to a separating funnel and the aqueous layer removed. The ethyl acetate layer was washed with saturated brine and then dried over magnesium sulphate. After filtration the solvent was evaporated to give the crude product as a yellow gum. The crude product was purified by preparative LCMS, using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (0.073 g, 15.48%) as a white solid.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07737149B2uspto-grants-2010_06