Pyrazole → HCID 52914255, compound

HRID 341035Notes

Reaction equation

HRID 341035 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(I)[CH:32]=[CH:31][CH:30]=[CH:29][CH2:28]4)[N:26]=[C:7]3[C:6]=2[C:5]([F:35])=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC.[NH:54]1[CH:58]=[CH:57][CH:56]=[N:55]1>CS(C)=O.O.[Cu]I>[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[N:54]4[CH:58]=[CH:57][CH:56]=[N:55]4)[N:26]=[C:7]3[C:6]=2[C:5]([F:35])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 1048PyrazoleHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 68154135HCID 68154135, compound

Product 1

HCID 52914255HCID 52914255, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

6,9-Difluoro-2-(1-iodophenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one [(Example 53), 36 mg, 0.062 mmol], potassium phosphate (40 mg, 0.19 mmol, 3 equiv), (±)-trans-N,N′-bismethyl-1,2-cyclohexane diamine (7.1 mg, 0.050 mmol, 0.8 equiv), copper(I) iodide (4.7 mg, 0.025 mmol, 0.4 equiv) and pyrazole (8.5 mg, 0.12 mmol, 2 equiv) were combined in dimethylsulfoxide (0.9 mL) and water (0.1 mL). The mixture was sparged under a nitrogen atmosphere, the vessel was sealed and placed into an preheated oil bath at 130° C. for 3 hours. The mixture was cooled to ambient temperature, poured into water (10 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (20:80 to 95:5; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid). The appropriate fractions were poured into sodium bicarbonate (50 mL, aqueous saturated) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 8.96 (1H, s), 8.46 (1H, d, J=2.6 Hz), 7.81 (2H, d, J=8.7 Hz), 7.76-7.68 (3H, m), 7.64-7.47 (5H, m), 7.40 (1H, td, J=8.9, 3.5 Hz), 7.30 (2H, d, J=8.6 Hz), 6.53 (1H, dd, J=2.4, 2.0 Hz), 6.34 (1H, dd, J=2.4, 1.9 Hz), 5.75 (2H, d, J=3.1 Hz) ppm; high resolution mass spectrometry (ES+) m/z 520.1697 [(M+H)+; calculated for C29H19F2N7O: 520.1692].

Workup

  1. customThe mixture was sparged under a nitrogen atmosphere
  2. customthe vessel was sealed
  3. additionpoured into water (10 mL)
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. dry with materialThe combined organic extracts were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative reverse phase HPLC (20:80 to 95:5; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid)
  9. additionThe appropriate fractions were poured into sodium bicarbonate (50 mL, aqueous saturated)
  10. extractionextracted with ethyl acetate (2×50 mL)
  11. dry with materialThe combined organic extracts were dried with sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5418c214345b43058163c0b5e4ad24ff
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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