반응 #2495287

ord-66f9fe96d3934222b47b54a2011dc9dc

반응 조건

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

후처리

  1. 1
    기타to afford Solution A66
  2. 2
    온도cooled to room temperature
  3. 3
    기타to afford Solution B66
  4. 4
    workup.ADDITIONSolution B66 was added to Solution A66
  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 (664 mg, 16.6 mmol) in N,N-dimethylformamide (5 mL) was added cyclopropanesulfonic acid amide (2.01 g, 16.6 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h to afford Solution A66. A solution of 4,4,8-trimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (0.9 g, 2.37 mmol) and 1,1′-carbonyldiimidazole (768 mg, 4.74 mmol) in N,N-dimethylformamide (5 mL) was stirred at 70° C. for 1 h and cooled to room temperature to afford Solution B66. Solution B66 was added to Solution A66 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 [4,4,8-trimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carbonyl]-amide (107 mg, 9%) as a brown solid: MS (ESI) M+1=484.2.

출처

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