반응 #45128

ord-6cfc24ee0cee4ac5bb6092064daa6710

반응 조건

온도
80°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 HPLC
  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-((3R,5S)-3,5-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 room temperature and then the mixture was heated at 80° C. under nitrogen for 4 h and then at 70° C. for 18 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 HPLC, 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 (0.154 g, 32.7%) as a white solid.

출처

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