Water → HCID 46861604, compound

HRID 241980Notes

Reaction equation

HRID 241980 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:33](=[O:34])[C:12]2=[N: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][CH:23]=3)[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=3[C:11]2=[N:10]1.O.[CH3:36][N:37](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:33](=[O:34])[C:12]3=[N: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:36]#[N:37]

Participants

6

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 46896509HCID 46896509, compound

Product 1

HCID 46861604HCID 46861604, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

2-(2-Bromo-6-fluorophenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 12) 46 mg, 0.089 mmol] was dissolved in degassed N,N-dimethylformamide (1.5 mL) and treated with zinc cyanide (18 mg, 0.15 mmol, 1.7 equiv) and bis(tri-tert-butylphosphine)palladium(0) (9.0 mg, 0.018 mmole, 0.2 equiv). The mixture was stirred under nitrogen at 100° C. for 30 minutes, cooled to ambient temperature, poured into water and extracted twice with ethyl acetate. The combined organic extracts were washed once with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 90:10; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.32 (1H, d, J=7.8 Hz), 7.90 (1H, s), 7.72 (2H, d, J=9.4 Hz), 7.67-7.51 (7H, m), 7.44 (2H, d, J=9.4 Hz), 6.47 (1H, s), 5.89 (2H, s) ppm; low resolution mass spectrometry (ES+) m/z 461.9 [(M+H)+; calculated for C26H16FN7O: 461.4].

Workup

  1. temperaturecooled to ambient temperature
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic extracts were washed once with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography (100:0 to 90:10; chloroform:methanol)

Sources & evidence

ORD record
ord-c925a5baf21147bd9391ed5e5e887e24
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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