Dimethylformamide → HCID 68154018, compound

HRID 341083Notes

Reaction equation

HRID 341083 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:34](=[O:35])[C:12]2=[CH:13][N:14]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([N:28]4[CH:32]=[CH:31][CH:30]=[N:29]4)=[CH:24][C:23]=3F)[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=3[C:11]2=[N:10]1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:42][N:43](C)C=O>[C-]#N.[Zn+2].[C-]#N.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>[F:8][C:4]1[C:3]([N:9]2[C:34](=[O:35])[C:12]3=[CH:13][N:14]([CH2:21][C:22]4[CH:23]=[CH:24][C:25]([N:28]5[CH:32]=[CH:31][CH:30]=[N:29]5)=[CH:26][CH:27]=4)[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[C:11]3=[N:10]2)=[C:2]([CH:7]=[CH:6][CH:5]=1)[C:42]#[N:43]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 68154079HCID 68154079, compound

Product 1

HCID 68154018HCID 68154018, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418851HCID 178418851, compoundCatalyst

Procedure

2-(2-Bromo-6-fluorophenyl)-5-{[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 666, 0.10 g, 0.19 mmol) and zinc(II) cyanide (46 mg, 0.39 mmol, 2 equiv) were dissolved in N,N-dimethylformamide (3.5 mL). The mixture was degassed, treated with bis(tri-tert-butylphosphine)palladium(0) (15 mg, 0.029 mmol, 0.15 equiv) and placed into an oil bath preheated to 100° C. for 1 hour. The mixture was cooled to ambient temperature, poured into sodium carbonate (15 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 5% methanol), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.24 (1H, s), 8.46 (1H, d, J=2.5 Hz), 8.21 (1H, dd, J=7.9, 1.3 Hz), 7.91 (1H, d, J=8.0 Hz), 7.89-7.80 (4H, m), 7.76-7.70 (2H, m), 7.68-7.64 (1H, m), 7.56 (1H, ap t, J=7.3 Hz), 7.50 (2H, d, J=8.5 Hz), 6.53 (1H, m), 5.79 (2H, s) ppm; high resolution mass spectrometry (ES+) m/z 461.1503 [(M+H)+; calculated for C27H18FN6O: 461.1521].

Workup

  1. customThe mixture was degassed
  2. customplaced into an oil bath
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. dry with materialThe combined organic extracts were dried 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 5% methanol)

Sources & evidence

ORD record
ord-13ddff046aad419b88ea56cc0307acf6
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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