Potassium Phosphate, Tribasic → 2-(2-fluoro-3-methylpyridin-4-yl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 449958Notes

Reaction equation

HRID 449958 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][N:13]3[C:22]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[C:16]4=[N:23][NH:24][C:25](=[O:26])[C:15]4=[N:14]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC.[F:45][C:46]1[C:51]([CH3:52])=[C:50](I)[CH:49]=[CH:48][N:47]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.[Cu]I>[F:45][C:46]1[C:51]([CH3:52])=[C:50]([N:24]2[C:25](=[O:26])[C:15]3=[N:14][N:13]([CH2:12][C:9]4[CH:10]=[CH:11][C:6]([N:1]5[CH:5]=[CH:4][CH:3]=[N:2]5)=[CH:7][CH:8]=4)[C:22]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[C:16]3=[N:23]2)[CH:49]=[CH:48][N:47]=1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 117762982-Fluoro-4-iodo-3-methylpyridineHCID 687857895-[4-(1H-Pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 468966142-(2-fluoro-3-methylpyridin-4-yl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

5-{[4-(1H-Pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one (25 mg, 0.073 mmol), copper(I)iodide (14 mg, 0.073 mmol, 1 equiv), tribasic potassium phosphate (93 mg, 0.44 mmol, 6.0 equiv), (±)-trans-N,N′-bismethyl-1,2-cyclohexanediamine (31 mg, 3.0 equiv) and 2-fluoro-4-iodo-3-picoline (52 mg, 0.22 mmol, 3.0 equiv) were combined in degassed N,N-dimethylformamide (3 mL) and the mixture was placed into an oil bath preheated to 110° C. for 1 hour. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (25 mL, aqueous saturated) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.32 (1H, d, J=8.1 Hz), 8.15 (1H, d, J=5.3 Hz), 7.91 (1H, d, J=2.5 Hz), 7.72 (2H, d, J=8.5 Hz), 7.72 (1H, m), 7.67-7.59 (3H, m), 7.46 (1H, m), 7.43 (2H, d, J=8.3 Hz), 6.47 (1H, m), 5.89 (2H, s), 2.37 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 452.1623 [(M+H)+; calculated for C25H19FN7O: 452.1630].

Workup

  1. customthe mixture was placed into an oil bath
  2. extractionextracted with ethyl acetate (3×50 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 silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-b6adac016b894dc794834fd1dd3f0073
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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