반응 #45089

ord-de893a7553984bbfafac5cf7164be6ed

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도heated at 65° C. for 6 h
  2. 2
    여과the mixture was filtered through celite
  3. 3
    기타The filtrate was transferred to a separating funnel
  4. 4
    기타the aqueous layer removed
  5. 5
    세척The ethyl acetate layer was washed with saturated brine
  6. 6
    건조dried over magnesium sulphate
  7. 7
    여과After filtration the solvent
  8. 8
    기타was evaporated
  9. 9
    기타to give the crude product as a yellow solid
  10. 10
    기타The crude product was purified by preparative HPLC
  11. 11
    workup.ADDITIONFractions containing the desired compound
  12. 12
    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-(4-methylpiperazin-1-yl)thiophene-2-carboxylate (0.254 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 20° C. under nitrogen. The reaction mixture was stirred at room temperature for 18 h and then heated at 65° C. for 6 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 solid. 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. 147 g, 32.1%) as a white solid.

출처

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