Potassium Carbonate → HCID 52914729, compound

HRID 341064Notes

Reaction equation

HRID 341064 reaction equation
O=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][CH:14]=2)[CH:4]=[C:3]1[C:24]([O:26]CC)=O.P(Cl)(Cl)(Cl)=O.[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=1[NH:42][NH2:43].C(=O)([O-])[O-].[K+].[K+]>>[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=1[N:42]1[C:24](=[O:26])[C:3]2=[CH:4][N:5]([CH2:12][C:13]3[CH:14]=[CH:15][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:17][CH:18]=3)[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[C:2]2=[N:43]1

Participants

5

Reactant 4

HCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 27789212,6-DifluorophenylhydrazineHCID 68154346HCID 68154346, compound

Product 1

HCID 52914729HCID 52914729, compound

Procedure

Ethyl 4-oxo-1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-1,4-dihydroquinoline-3-carboxylate (0.10 g, 0.27 mmol) was dissolved in phosphorus oxychloride (0.75 mL, 8.0 mmol, 30 equiv) and stirred vigorously for 1 hour at ambient temperature. The mixture was concentrated in vacuo and the residue was concentrated from toluene (3×10 mL). The resulting 4-chloro-3-[(ethyloxy)carbonyl]-1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}quinolinium salt was dissolved in N,N-dimethylformamide (3 mL) and treated with (2,6-difluorophenyl)hydrazine (92 mg, 0.64 mmol, 2.5 equiv) and potassium carbonate (0.18 g, 1.3 mmol, 5 equiv). The mixture was placed into an oil bath preheated to 80° C. for 1 hour, cooled to ambient temperature and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (82:20 to 5:95; water containing 0.05% trifluoroacetic acid:acetonitrile containing 0.05% trifluoroacetic acid), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.18 (1H, s), 8.46 (1H, d, J=2.5 Hz), 8.18 (1H, dd, J=7.9, 1.3 Hz), 7.83 (2H, d, J=8.7 Hz), 7.78 (1H, d, J=9.0 Hz), 7.72 (1H, d, J=1.6 Hz), 7.66-7.57 (2H, m), 7.53 (1H, t, J=7.4 Hz), 7.48 (2H, d, J=8.5 Hz), 7.34 (2H, t, J=8.3 Hz), 6.53 (1H, dd, J=2.4, 1.8 Hz), 5.78 (2H, s) ppm; low resolution mass spectrometry (ES+) m/z 453.9 [(M+H)+; calculated for C26H18F2N5O: 454.1].

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. concentrationthe residue was concentrated from toluene (3×10 mL)
  3. dissolutionThe resulting 4-chloro-3-[(ethyloxy)carbonyl]-1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}quinolinium salt was dissolved in N,N-dimethylformamide (3 mL)
  4. customThe mixture was placed into an oil bath
  5. waitpreheated to 80° C. for 1 hour
  6. temperaturecooled to ambient temperature
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative reverse phase HPLC (82:20 to 5:95; water containing 0.05% trifluoroacetic acid:acetonitrile containing 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-369a266f3fbd462bb0a876bad71469e4
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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