Potassium Phosphate, Tribasic → 2-(2,3-dimethylphenyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 449966

Reaction equation

HRID 449966 reaction equation
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][N:11]3[C:20]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[C:14]4=[N:21][NH:22][C:23](=[O:24])[C:13]4=[N:12]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.I[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:29]=1[CH3:35].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC.C(=O)(O)[O-].[Na+]>[Cu]I.CN(C)C=O>[CH3:35][C:29]1[C:30]([CH3:34])=[CH:31][CH:32]=[CH:33][C:28]=1[N:22]1[C:23](=[O:24])[C:13]2=[N:12][N:11]([CH2:10][C:9]3[CH:8]=[CH:7][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:26][CH:25]=3)[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:14]2=[N:21]1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 1416452,3-DimethyliodobenzeneHCID 516892Sodium BicarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 687857895-[4-(1H-Pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 468967082-(2,3-dimethylphenyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-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)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one (75 mg, 0.22 mmol) was dissolved in degassed. NA-dimethylformamide and treated with 1-iodo-2,3-dimethylbenzene (0.15 g, 0.66 mmol, 3 equiv), tribasic potassium phosphate (0.28 g, 1.31 mmol, 6 equiv), copper(I)iodide (42 mg, 0.22 mmol, 1 equiv) and (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (93 mg, 0.66 mmol, 3 equiv). The mixture was placed into an oil bath preheated at 110° C. for 30 minutes, cooled to ambient temperature, poured into sodium bicarbonate (25 mL, saturated aqueous) 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 via silica gel gradient chromatography (60:40 to 0:100; hexanes:ethyl acetate), providing the titled compound. 1H-NMR (400 MHz, CDCl3) δ 8.33-8.30 (1H, m), 7.90 (1H, d, J=2.6 Hz), 7.73-7.69 (3H, m), 7.58-7.52 (3H, m), 7.43 (2H, d, J=8.7 Hz), 7.31-7.27 (1H, m), 7.24-7.22 (2H, m), 6.47 (1H, dd, J=2.5, 1.8 Hz), 5.88 (2H, s), 2.37 (3H, s), 2.21 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 447.1931 [(M+H)+; calculated for C27H22N6O: 447.1928].

Workup

  1. customin degassed
  2. customThe mixture was placed into an oil bath
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via silica gel gradient chromatography (60:40 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-cbef217fda0c4ce2b6384882e56dfe42
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Linked notes

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