Imidazole → 5-{[6-(1H-Imidazol-1-yl)pyridine-3-yl]methyl}-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 241991Notes

Reaction equation

HRID 241991 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]=[CH:25][C:24]=4[CH3:29])[C:21](=[O:22])[C:11]3=[N:10]2)=[CH:4][CH:3]=1.[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I.O>[N:30]1([C:2]2[N:7]=[CH:6][C:5]([CH2:8][N:9]3[C:18]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[C:12]4=[N:19][N:20]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[CH3:29])[C:21](=[O:22])[C:11]4=[N:10]3)=[CH:4][CH:3]=2)[CH:34]=[CH:33][N:32]=[CH:31]1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 468966115-[(6-Bromopyridin-3-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 468966125-{[6-(1H-Imidazol-1-yl)pyridine-3-yl]methyl}-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 3

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

Procedure

5-[(6-Bromopyridin-3-yl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 22) 80 mg, 0.18 mmol] was dissolved in dimethyl sulfoxide (1 mL) and treated with imidazole (49 mg, 0.72 mmol, 4 equiv), copper (I) iodide (14 mg, 0.072 mmol, 0.4 equiv), and (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (20 mg, 0.14 mmol, 0.8 equiv). An aqueous solution (0.2 mL) of tribasic potassium phosphate (0.11 g, 0.54 mmol, 3 equiv) was added and the mixture was placed into a preheated oil bath at 75° C. for 2 hours. The mixture was cooled to ambient temperature, poured into water and extracted twice with ethyl acetate. The combined organic extracts were washed once with water and brine, dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 94:6; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.58 (1H, s), 8.43 (1H, br s), 8.33 (1H, d, J=6.9 Hz), 7.85 (1H, d, J=9.7 Hz), 7.77 (1H, br s), 7.68-7.54 (3H, m), 7.45 (1H, m), 7.38-7.32 (5H, m), 5.88 (2H, s), 2.36 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 434.1736 [(M+H)+; calculated for C25H20N7O: 434.1724].

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic extracts were washed once with water and brine
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel gradient chromatography (100:0 to 94:6; chloroform:methanol)

Sources & evidence

ORD record
ord-939d7fce9456496a9c220beefefac2ce
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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