Cesium carbonate → HCID 68153871, compound

HRID 341098Notes

Reaction equation

HRID 341098 reaction equation
[F:1][C:2]1[C:11]2[N:10]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)[CH:9]=[C:8]3[C:24](=[O:34])[N:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[N:26]=[C:7]3[C:6]=2[C:5](F)=[CH:4][CH:3]=1.[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41]([CH2:44][NH2:45])=[CH:40][CH:39]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)(O)[O-].[Na+]>CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:45]([CH2:44][C:41]3[CH:42]=[CH:43][C:38]([O:37][CH3:36])=[CH:39][CH:40]=3)[CH:9]=[C:8]3[C:24](=[O:34])[N:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[N:26]=[C:7]3[C:6]=2[C:11]=1[NH:10][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH:23]=[CH:22][CH:21]=[N:20]2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 754524-MethoxybenzylamineHCID 516892Sodium BicarbonateHCID 57328758HCID 57328758, compound

Product 1

HCID 68153871HCID 68153871, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

6,9-Difluoro-2-(2-methylphenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 29, 12 mg, 0.026 mmol), 1-[4-(methyloxy)phenyl]methanamine (5.3 mg, 0.039 mmol, 1.5 equiv) and cesium carbonate (12 mg, 0.039 mmol, 1.5 equiv) were combined in dimethylsulfoxide (2 mL) and placed into an oil bath preheated at 70° C. for 1 hour. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (50 mL, aqueous saturated) and extracted with ethyl acetate (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative HPLC (80:20 to 5:95; water containing 0.5% trifluoroacetic acid:acetonitrile containing 0.5% trifluoroacetic acid). The appropriate fractions were poured into sodium bicarbonate (75 mL, aqueous saturated) and extracted with ethyl acetate (1×100 mL). The organic extract was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound as a yellow foam: 1H-NMR (4001 MHz, CDCl3) δ 8.35 (1H, s), 8.35-8.29 (1H, m), 7.85 (1H, d, J=2.5 Hz), 7.69 (1H, d, J=1.6 Hz), 7.56 (2H, d, J=8.5 Hz), 7.45 (1H, dd, J=5.3, 4.1 Hz), 7.42 (2H, d, J=8.5 Hz), 7.33-7.27 (3H, m), 7.14 (2H, d, J=8.7 Hz), 7.05 (1H, dd, J=13.2, 9.0 Hz), 6.90 (2H, d, J=8.7 Hz), 6.68 (1H, dd, J=9.4, 3.4 Hz), 6.44-6.43 (1H, m), 5.29 (2H, s), 4.77 (2H, m), 3.80 (3H, s), 2.31 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 585.2417 [(M+H)+; calculated for C35H30FN6O2: 585.2409].

Workup

  1. customplaced into an oil bath
  2. extractionextracted with ethyl acetate (2×75 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (80:20 to 5:95; water containing 0.5% trifluoroacetic acid:acetonitrile containing 0.5% trifluoroacetic acid)
  7. additionThe appropriate fractions were poured into sodium bicarbonate (75 mL, aqueous saturated)
  8. extractionextracted with ethyl acetate (1×100 mL)
  9. extractionThe organic extract
  10. dry with materialwas dried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ce3a389865564bb5838d1c323b8fa49d
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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