Cesium carbonate → 2-(2,3-dimethylphenyl)-5-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 242027Notes

Reaction equation

HRID 242027 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3=[N:19][N:20]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[C:24]=4[CH3:30])[C:21](=[O:22])[C:11]3=[N:10]2)=[CH:4][CH:3]=1.[CH3:31][C:32]1[N:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)(O)[O-].[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Cu]Cl>[CH3:30][C:24]1[C:25]([CH3:29])=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[N:10][N:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([C:35]4[CH:36]=[N:37][C:32]([CH3:31])=[CH:33][CH:34]=4)=[N:7][CH:6]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 866818455-[(6-Bromopyridin-3-yl)methyl]-2-(2,3-dimethylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 585421052-(2,3-dimethylphenyl)-5-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Procedure

5-[(6-Bromopyridin-3-yl)methyl]-2-(2,3-dimethylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one (0.10 g, 0.22 mmol), (6-methylpyridin-3-yl)-boronic acid (74 mg, 0.54 mmol, 2.5 equiv), palladium(II)acetate (9.7 mg, 0.043 mmol, 0.2 equiv), 1,1′-bis(diphenylphosphino)ferrocene (24 mg, 0.043 mmol, 0.2 equiv), copper(I)chloride (21 mg, 0.22 mmol, 1 equiv) and cesium carbonate (0.18 g, 0.54 mmol, 2.5 equiv) were combined in N,N-dimethylformamide (4 mL) and placed into an oil bath preheated to 100° C. for 60 minutes. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (20 mL, aqueous saturated) and extracted with ethyl acetate (3×25 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 90:10; dichloromethane:methanol), providing the titled compound as a deep red solid: 1H-NMR (400 MHz, CDCl3) δ 9.06 (1H, d, J=2.1 Hz), 8.78 (1H, d, J=1.7 Hz), 8.32 (1H, dd, J=7.8, 1.0 Hz), 8.19 (1H, dd, J=8.1, 2.3 Hz), 7.77 (1H, dd, J=8.3, 2.4 Hz), 7.72 (1H, d, J=8.3 Hz), 7.65-7.54 (3H, m), 7.42-7.38 (1H, m), 7.30-7.22 (3H, m), 5.90 (2H, s), 2.61 (3H, s), 2.37 (3H, s), 2.20 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 473.2099 [(M+H)+; calculated for C29H25N6O: 473.2084].

Workup

  1. customplaced into an oil bath
  2. extractionextracted with ethyl acetate (3×25 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 chromatography (100:0 to 90:10; dichloromethane:methanol)

Sources & evidence

ORD record
ord-c56ef52c29814918811583335010c186
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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