Biphenyl-2-boronic acid → 2-biphenyl-2-yl-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one

HRID 1454970Notes

Reaction equation

HRID 1454970 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][C:10](=[O:20])[C:11]=2[C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[F:19])[N:7]=1.[C:21]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]1([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[CH:9][C:10](=[O:20])[C:11]=2[C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[F:19])[N:7]=1

Participants

4

Reactant 2

HCID 4589187Biphenyl-2-boronic acidHCID 575312262-chloro-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one

Product 1

HCID 167499582-biphenyl-2-yl-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

2-chloro-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one (50 g, 0.17 mmol), biphenyl-2-ylboronic acid (51.4 mg, 0.26 mmol), and Tetrakis (19.6 g, 0.017 mmol) were added to a flask and purged with N2 (3×). After the addition of toluene (5 mL), ethanol (0.5 mL), and 2M Na2CO3 (0.5 mL) the resulting mixture was heated to 90° C. for 1 hour. The reaction was concentrated in vacuo and the crude residue was dissolved in H2O/EtOAc (1:1) and extracted with H2O, 1N HCl (2×), brine (2×), dried over MgSO4, and concentrated in vacuo to yield an oil. The crude material was purified via silica gel chromatography (CH2Cl2/EtOAc/MeOH) to yield the title compound.

Workup

  1. custompurged with N2 (3×)
  2. additionAfter the addition of toluene (5 mL), ethanol (0.5 mL), and 2M Na2CO3 (0.5 mL) the resulting mixture
  3. concentrationThe reaction was concentrated in vacuo
  4. dissolutionthe crude residue was dissolved in H2O/EtOAc (1:1)
  5. extractionextracted with H2O, 1N HCl (2×), brine (2×)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto yield an oil
  9. customThe crude material was purified via silica gel chromatography (CH2Cl2/EtOAc/MeOH)

Sources & evidence

ORD record
ord-daa5d0327c964cf583f641bb8b90e033
Source dataset
uspto-grants-2009_01
Patent number
US07482345B2

Reaction notes

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