Diethyl Ether → HCID 22120922, compound

HRID 1108815Notes

Reaction equation

HRID 1108815 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 wAas 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 wvas then poured into ether (25 ml) and water (25 ml). The layers ere 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 wAas 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 wvas
  9. customThe layers ere 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-ea3f5f0a10f74a49a7b578cb5ca507aa
Source dataset
uspto-grants-2000_05
Patent number
US06069157

Reaction notes

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