Diethyl Ether → HCID 22120922, compound

HRID 1274335Notes

Reaction equation

HRID 1274335 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1I.C(=O)([O-])O.[Na+].[S:27]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28]1.CCOCC>C1(C)C=CC=CC=1.C(O)C.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.O>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:29]1[CH:30]=[CH:31][S:27][CH:28]=1

Participants

9

Reactant 4

HCID 3283Diethyl EtherHCID 516892Sodium Bicarbonate2×HCID 581760Thiophene-3-boronic acid2×HCID 154620775-Amino-3-cyano-4-iodo-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]pyrazole

Product 1

HCID 22120922HCID 22120922, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalyst3×HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a rapidly stirred solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (0.447 g) in toluene (2 ml) containing tetrakis(triphenylphosphine)palladium(0) (0.02 g) was added saturated aqueous sodium hydrogen carbonate solution (1 ml) and a solution of thiophene-3-boronic acid (0.256 g) in ethanol (1 ml). The mixture was heated under reflux for 3 hours, then left at room temperature overnight. Saturated aqueous sodium hydrogen carbonate solution (0.5 ml) and tetrakis(triphenylphosphine)palladium(0) (0.01 g) were added and the mixture heated under reflux for 3 hours. Thiophene-3-boronic acid (0.178 g) and tetrakis(triphenylphosphine)palladium(0) (0.02 g) were added and heating under reflux continued for 16 hours. The cooled reaction mixture was then poured into ether (25 ml) and water (25 ml). The layers were separated and the aqueous phase extracted with a second portion of ether (25 ml). The combined organic layers were washed with water (2×25 ml), brine (25 ml) and then dried (MgSO4) and evaporated. The residue was purified by column chromatography on silica gel (50 g) eluted with dichloromethane. Combination and evaporation of suitable fractions gave the title compound as a white crystalline solid, m.p. 210-2° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 3 hours
  3. temperaturethe mixture heated
  4. temperatureunder reflux for 3 hours
  5. temperatureheating
  6. temperatureunder reflux
  7. waitcontinued for 16 hours
  8. customThe cooled reaction mixture
  9. customThe layers were separated
  10. extractionthe aqueous phase extracted with a second portion of ether (25 ml)
  11. washThe combined organic layers were washed with water (2×25 ml), brine (25 ml)
  12. dry with materialdried (MgSO4)
  13. customevaporated
  14. customThe residue was purified by column chromatography on silica gel (50 g)
  15. washeluted with dichloromethane
  16. customCombination and evaporation of suitable fractions

Sources & evidence

ORD record
ord-4d3dd41c150241cfbda0ea558c5d6efa
Source dataset
uspto-grants-2000_12
Patent number
US06156782

Reaction notes

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