Nitrogen → HCID 58486414, compound

HRID 1890760Notes

Reaction equation

HRID 1890760 reaction equation
N#N.Cl[C:4]1[N:9]=[N:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:12][CH2:11]2)=[C:6]([CH3:25])[C:5]=1[CH3:26].[F:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.[F-].[Cs+]>O1CCOCC1>[F:27][C:28]1[CH:33]=[CH:32][C:31]([C:4]2[N:9]=[N:8][C:7]([N:10]3[CH2:15][CH2:14][CH:13]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:12][CH2:11]3)=[C:6]([CH3:25])[C:5]=2[CH3:26])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 25953Cesium fluorideHCID 2856454-Fluorophenylboronic acidHCID 58486430HCID 58486430, compound

Product 1

HCID 58486414HCID 58486414, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

Treat a N2 degassed mixture of tert-butyl 1-(6-chloro-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate (3.01 g, 8.48 mmol), 4-fluorophenylboronic acid (1.23 g, 8.80 mmol) and CsF (4.08 g, 26.8 mmol) in 1,4-dioxane (80 mL) with (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) chloride (1.10 g, 1.35 mmol). Heat the resulting mixture under N2 at 95° C. overnight. Partition the reaction mixture between H2O and EtOAc. Separate the layers, and wash the organic layer with brine. Dry the organic layer over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 20 to 80% EtOAc in hexanes) to provide the title compound (3.05 g, 87%). ES/MS m/z 415.2 (M+1).

Workup

  1. customdegassed
  2. customPartition the reaction mixture between H2O and EtOAc
  3. customSeparate the layers
  4. washwash the organic layer with brine
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue by flash silica gel chromatography (gradient of 20 to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5288860a365843d2b32deea83aad87cc
Source dataset
uspto-grants-2013_08
Patent number
US08507490B2

Reaction notes

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