Cesium carbonate → HCID 178423747, compound

HRID 341096Notes

Reaction equation

HRID 341096 reaction equation
[OH:1][C:2]1[C:3]2[C:4]3[C:5]([C:20](=[O:30])[N:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])[N:22]=3)=[CH:6][N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3I)[C:8]=2[CH:9]=[CH:10][CH:11]=1.[CH3:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][N:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1C=CC(B(O)O)=CN=1.B(O)O.C(=O)(O)[O-].[Na+]>O1CCCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.[Cu]Cl.O>[OH:1][C:2]1[C:3]2[C:4]3[C:5]([C:20](=[O:30])[N:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])[N:22]=3)=[CH:6][N:7]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:35]4[CH:34]=[N:33][C:32]([CH3:31])=[CH:37][CH:36]=4)=[CH:15][CH:14]=3)[C:8]=2[CH:9]=[CH:10][CH:11]=1

Participants

10

Reactant 5

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 178423578HCID 178423578, compoundHCID 178424335HCID 178424335, compound

Product 1

HCID 178423747HCID 178423747, compound

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 178418851HCID 178418851, compoundCatalyst2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

9-Hydroxy-5-[(iodophenyl)methyl]-2-(2-methylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 728, 0.28 g, 0.56 mmol) was dissolved in tetrahydrofuran (5 mL) and treated with bis(tri-tert-butylphosphine)palladium(0) (57 mg, 0.11 mmol, 0.2 equiv), copper(I) chloride (55 mg, 0.56 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (0.15 g, 1.1 mmol, 2 equiv) and an aqueous solution (2 mL) of cesium carbonate (0.45 g, 1.4 mmol, 2.5 equiv). The mixture was placed into a preheated oil bath at 70° C. for 2 hours, charged with additional boronic acid 2-methyl-5-pyridinylboronic acid (75 mg, 0.56 mmol, 1 equiv) and bis(tri-tert-butylphosphine)palladium(0) (27 mg, 0.056 mmol, 0.1 equiv). The mixture was heated for an additional 3 hours at 70° C., cooled to ambient temperature, poured into sodium bicarbonate (50 mL, aqueous saturated) and water (100 mL) and extracted with ethyl acetate (2×75 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 as a light yellow solid: 1H-NMR (400 MHz, CDCl3) δ 9.72 (1H, br s), 8.70 (1H, d, J=2.1 Hz), 8.45 (1H, s), 7.74 (1H, dd, J=8.0, 2.3 Hz), 7.58 (2H, d, J=8.0 Hz), 7.50-7.21 (4H, br m), 7.46 (1H, br m), 7.33 (2H, d, J=8.2 Hz), 7.23 (1H, d, J=8.0 Hz), 7.01 (1H, br s), 5.46 (2H, s), 2.60 (3H, s), 2.35 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 473.1985 [(M+H)+; calculated for C30H25N4O2: 473.1972].

Workup

  1. temperaturecooled to ambient temperature
  2. extractionextracted with ethyl acetate (2×75 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-d778763bc9044c3d81e94b6879a7b488
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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