Cesium fluoride → HCID 136200885, compound

HRID 1619662Notes

Reaction equation

HRID 1619662 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5](I)=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=1.C([Sn](CCCC)(CCCC)[C:25]1[CH:30]=[CH:29][N:28]=[N:27][CH:26]=1)CCC.[F-].[Cs+]>C(#N)C.[Cu](I)I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([C:25]2[CH:30]=[CH:29][N:28]=[N:27][CH:26]=2)=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 58042300HCID 58042300, compound

Product 1

HCID 136200885HCID 136200885, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

2-Chloro-5-iodo-3′-(trifluoromethyl)biphenyl-4-ol (Preparation 51, 230 mg, 0.57 mmol) was dissolved in acetonitrile (3 mL), 4-(tributylstannyl)pyridazine (273 mg, 0.75 mmol), caesium fluoride (173 mg, 1.14 mmol), copper iodide (22 mg, 0.114 mmol) and tetrakis(triphenylphosphine)palladium (0) (70 mg, 0.06 mmol) were added. The reaction was stirred at 45° C. for 1.5 hours and then after cooling to room temperature was partitioned between ethyl acetate (100 mL) and water (50 mL) containing 0.880 ammonia (1 mL). The mixture was stirred for 20 minutes. The ethyl acetate phase was separated and washed with an aqueous solution of potassium fluoride (1.5 g in 20 mL), 1M hydrochloric acid (20 mL) and aqueous ammonia (1 mL 0.880 in 50 mL water). The ethyl acetate was dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica eluting with a gradient of dichloromethane:methanol 100:0 to 95:5 to give the title compound (144 mg, 0.40 mmol, 71%) as a white solid.

Workup

  1. temperatureafter cooling to room temperature
  2. customwas partitioned between ethyl acetate (100 mL) and water (50 mL)
  3. additioncontaining 0.880 ammonia (1 mL)
  4. stirringThe mixture was stirred for 20 minutes
  5. customThe ethyl acetate phase was separated
  6. washwashed with an aqueous solution of potassium fluoride (1.5 g in 20 mL), 1M hydrochloric acid (20 mL) and aqueous ammonia (1 mL 0.880 in 50 mL water)
  7. dry with materialThe ethyl acetate was dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was chromatographed on silica eluting with a gradient of dichloromethane:methanol 100:0 to 95:5

Sources & evidence

ORD record
ord-a86daddfbec14267a09ba3f62a433b10
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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