반응 #2495255

ord-c475ddef6721466bbd8ff9e7bfc19f9c

반응 조건

온도
25°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타to afford Solution A52
  2. 2
    온도cooled to room temperature
  3. 3
    기타to afford Solution B52
  4. 4
    workup.ADDITIONSolution B52 was added to Solution A52
  5. 5
    workup.STIRRINGthe resulting mixture was stirred at 25° C. for 1 h
  6. 6
    여과The mixture was filtered
  7. 7
    기타to remove the insoluble solid
  8. 8
    기타the filtrate was purified by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water)

실험 절차

To a suspension of 60% sodium hydride (800 mg, 20 mmol) in N,N-dimethylformamide (4 mL) was added cyclopropanesulfonic acid amide (2.4 g, 20 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h to afford Solution A52. A solution of 4,4-dimethyl-2-(3-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (1 g, 2.86 mmol) and 1,1′-carbonyldiimidazole (930 mg, 5.71 mmol) in N,N-dimethylformamide (3 mL) was stirred at 70° C. for 1 h and cooled to room temperature to afford Solution B52. Solution B52 was added to Solution A52 and the resulting mixture was stirred at 25° C. for 1 h. To the reaction mixture was added water (0.5 mL). The mixture was filtered to remove the insoluble solid, and the filtrate was purified by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded cyclopropanesulfonic acid [4,4-dimethyl-2-(3-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amide (107 mg, 8%) as a brown solid: MS (ESI) M+1=454.2.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08809369B2uspto-grants-2014_08