Potassium Phosphate, Tribasic → HCID 49763232, compound

HRID 2067101Notes

Reaction equation

HRID 2067101 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[N:12]=[CH:11][C:10]([CH2:13][N:14]3[C:19]4[N:20]=[CH:21][CH:22]=[CH:23][C:18]=4[C:17]4=[N:24][NH:25][C:26](=[O:27])[C:16]4=[N:15]3)=[CH:9][CH:8]=2)[CH:4]=[N:3]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC.I[C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([CH3:53])[C:48]=1[CH3:54].C(=O)(O)[O-].[Na+]>CN(C)C=O.[Cu]I>[CH3:54][C:48]1[C:49]([CH3:53])=[CH:50][CH:51]=[CH:52][C:47]=1[N:25]1[C:26](=[O:27])[C:16]2=[N:15][N:14]([CH2:13][C:10]3[CH:11]=[N:12][C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)=[CH:8][CH:9]=3)[C:19]3[N:20]=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]2=[N:24]1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 1416452,3-DimethyliodobenzeneHCID 516892Sodium BicarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 66745538HCID 66745538, compound

Product 1

HCID 49763232HCID 49763232, compound

Reagents, catalysts & solvents 2

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

Procedure

5-{[6-(1-Methyl-1H-pyrazol-4-yl)pyridin-3-yl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one (50 mg, 0.14 mmol), copper(I) iodide (27 mg, 0.14 mmol, 1 equiv), potassium phosphate (0.18 g, 0.84 mmol, 6 equiv), (±)-trans-N,N′-bismethyl-1,2-cyclohexanediamine (59 mg, 0.42 mmol, 3 equiv) and 3-iodo-ortho-xylene (59 μL, 0.42 mmol, 3 equiv) were combined in degassed N,N-dimethylformamide (2.5 mL) and placed into an oil bath preheated to 110° C. for 30 minutes. 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 containing 10% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.83 (1H, d, J=2.2 Hz), 8.78 (1H, dd, J=4.6, 1.7 Hz), 8.54 (1H, dd, J=8.0, 1.9 Hz), 7.92 (1H, dd, J=7.9, 2.2 Hz), 7.91 (1H, s), 7.89 (1H, s), 7.51 (1H, dd, J=8.0, 4.6 Hz), 7.41 (1H, d, J=8.3 Hz), 7.26 (1H, br s), 7.23-7.21 (2H, m), 5.96 (2H, s), 3.94 (3H, s), 2.36 (3H, s), 2.16 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 463.1986 [(M+H)+; calculated for C26H23N8O: 463.1989].

Workup

  1. customplaced 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 containing 10% methanol)

Sources & evidence

ORD record
ord-d4e1ef8d8a894250a610604c45eecfca
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

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