반응 #2495267

ord-7e6afb4aff91459abb83bd8aa7602071

반응 조건

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

후처리

  1. 1
    기타to afford Solution A56
  2. 2
    온도cooled to room temperature
  3. 3
    기타to afford Solution B56
  4. 4
    workup.ADDITIONSolution B56 was added to Solution A56
  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 (360 mg, 9 mmol) in N,N-dimethylformamide (5 mL) was added methanesulfonamide (865 mg, 9.1 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h to afford Solution A56. A solution of 6-fluoro-4,4-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid (500 mg, 1.3 mmol) and 1,1′-carbonyldiimidazole (422 mg, 2.6 mmol) in N,N-dimethylformamide (3 mL) was stirred at 70° C. for 1 h and cooled to room temperature to afford Solution B56. Solution B56 was added to Solution A56 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 N-[6-fluoro-4,4-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-8-carbonyl]-methanesulfonamide (270 mg, 45%) as a white solid: MS (ESI) M+1=462.1.

출처

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