Potassium Phosphate, Tribasic → HCID 49763346, compound

HRID 2067110Notes

Reaction equation

HRID 2067110 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]3[C:20]4[N:21]=[CH:22][CH:23]=[CH:24][C:19]=4[C:18]4=[N:25][NH:26][C:27](=[O:28])[C:17]4=[N:16]3)=[CH:10][N:9]=2)=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC.[F:47][C:48]1[C:53]([CH3:54])=[CH:52][CH:51]=[CH:50][C:49]=1I.C(=O)(O)[O-].[Na+]>CN(C)C=O.[Cu]I>[F:47][C:48]1[C:53]([CH3:54])=[CH:52][CH:51]=[CH:50][C:49]=1[N:26]1[C:27](=[O:28])[C:17]2=[N:16][N:15]([CH2:14][C:11]3[CH:12]=[CH:13][C:8]([C:5]4[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=4)=[N:9][CH:10]=3)[C:20]3[N:21]=[CH:22][CH:23]=[CH:24][C:19]=3[C:18]2=[N:25]1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 248205372-Fluoro-1-iodo-3-methylbenzeneHCID 66744389HCID 66744389, compound

Product 1

HCID 49763346HCID 49763346, compound

Reagents, catalysts & solvents 2

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

Procedure

5-[(6′-Methyl-2,3′-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazine-3-one (40 mg, 0.11 mmol), copper(I) iodide (21 mg, 0.11 mmol, 1 equiv), potassium phosphate (0.14 g, 0.65 mmol, 6 equiv), (±)-trans-N,N′-bismethyl-1,2-cyclohexanediamine (46 mg, 0.32 mmol, 3 equiv) and 2-fluoro-1-iodo-3-methylbenzene (64 mg, 0.27 mmol, 2.5 equiv) were combined in degassed N,N-dimethylformamide (2.5 mL) and placed into an oil bath preheated to 110° C. for 45 min. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (100 mL, aqueous saturated) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed once with brine (50 mL), 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 as a red solid: 1H-NMR (400 MHz, CDCl3) δ 9.04 (1H, d, J=1.8 Hz), 8.97 (1H, d, J=1.7 Hz), 8.79 (1H, dd, J=4.6, 1.9 Hz), 8.56 (1H, dd, J=8.0, 1.8 Hz), 8.18 (1H, dd, J=8.1, 2.2 Hz), 8.01 (1H, dd, J=8.2, 2.3 Hz), 7.70 (1H, dd, J=8.2, 0.6 Hz), 7.52 (1H, dd, J=8.0, 4.6 Hz), 7.41-7.37 (1H, ), 7.27-7.22 (2H, m), 7.15 (1H, ap t, J=7.9 Hz), 6.01 (2H, s), 2.60 (3H, s), 2.36 (1H, J=2.0 Hz) ppm; high resolution mass spectrometry (ES+) m/z 478.1783 [(M+H)+; calculated for C27H21FN7O: 478.1786].

Workup

  1. customplaced into an oil bath
  2. extractionextracted with ethyl acetate (3×75 mL)
  3. washThe combined organic extracts were washed once with brine (50 mL)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. 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-b62d1718a9bb44f6968dce780cc6b784
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

Loading…