Potassium Phosphate, Tribasic → 2-(2,3-Dimethylphenyl)-5-{[6-(1,3-thiazol-4-yl)pyridin-3-yl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 242025

Reaction equation

HRID 242025 reaction equation
[S:1]1[CH:5]=[C:4]([C:6]2[N: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)[N:3]=[CH:2]1.I[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:29]=1[CH3:35].CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.O.[Cu]I>[CH3:35][C:29]1[C:30]([CH3:34])=[CH:31][CH:32]=[CH:33][C:28]=1[N:24]1[C:25](=[O:26])[C:15]2=[N:14][N:13]([CH2:12][C:9]3[CH:10]=[N:11][C:6]([C:4]4[N:3]=[CH:2][S:1][CH:5]=4)=[CH:7][CH:8]=3)[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16]2=[N:23]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 1416452,3-DimethyliodobenzeneHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 86660007HCID 86660007, compound

Product 1

HCID 468970142-(2,3-Dimethylphenyl)-5-{[6-(1,3-thiazol-4-yl)pyridin-3-yl]methyl}-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 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-{[6-(1,3-Thiazol-4-yl)pyridin-3-yl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one (66 mg, 0.18 mmol) was dissolved in degassed N,N-dimethylformamide (1 mL) and copper (I) iodide (35 mg, 0.22 mmol, 1.2 equiv), 1-iodo-2,3-dimethylbenzene (51 mg, 0.22 mmol, 1.2 equiv), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (78 mg, 0.549 mmol, 3 equiv) and potassium phosphate (0.27 g, 1.3 mmol, 7 equiv) were added. The vessel was sealed and placed into an oil bath preheated at 105° C. for 40 minutes. The mixture cooled to ambient temperature, diluted with water (5 mL) and extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed three times with water and once with brine, dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 96:4; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.87 (1H, s), 8.69 (1H, s), 8.31 (1H, d, J=8.2 Hz), 8.16 (2H, m), 7.77 (1H, d, J=8.2 Hz), 7.57 (4H, m), 7.28 (1H, m), 7.22 (1H, d, J=3.9 Hz), 5.90 (2H, s), 2.37 (3H, s), 2.21 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 465.1499 [(M+H)+; calculated for C26H21N6OS: 465.1492].

Workup

  1. customThe vessel was sealed
  2. customplaced into an oil bath
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. washThe combined organic extracts were washed three times with water
  5. dry with materialonce with brine, dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel gradient chromatography (100:0 to 96:4; chloroform:methanol)

Sources & evidence

ORD record
ord-59e5ed3b13fb4f53841c91f63b62f296
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Linked notes

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