Potassium Carbonate → HCID 44610524, compound

HRID 1967159Notes

Reaction equation

HRID 1967159 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:10]2[C:15]([F:16])=[CH:14][C:13]([C:17]([OH:20])([CH3:19])[CH3:18])=[CH:12][C:11]=2[F:21])=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].I[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>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]>[NH:1]([C:2]1[S:3][C:4]([C:10]2[C:11]([F:21])=[CH:12][C:13]([C:17]([OH:20])([CH3:18])[CH3:19])=[CH:14][C:15]=2[F:16])=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 11575IodobenzeneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 595256192-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

Product 1

HCID 44610524HCID 44610524, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A sealed tube was charged with a stir bar and 2-amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (150 mg, 0.480 mmol) and iodobenzene (98 mg, 0.480 mmol), Pd2(dba)3 (44 mg, 0.048 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (114 mg, 0.240 mmol), and potassium carbonate (73 mg, 0.528 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed tert-amyl alcohol (1.6 mL) was added to the mixture via syringe. The solution was sealed and stirred overnight in an oil bath at 100° C. The following day, the reaction was allowed to cool to room temperature, taken up in ethyl acetate, and washed with aqueous sodium bicarbonate and brine. The organic layers were collected, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification was conducted via silica gel chromatography (0-3% methanol in ethyl acetate). Fractions containing product were concentrated under reduced pressure, taken up in ethyl acetate and methanol, and recrystallized out using hexanes to yield the title product.

Workup

  1. additionA sealed tube was charged with a stir bar
  2. customThe tube was evacuated
  3. additionFully degassed tert-amyl alcohol (1.6 mL) was added to the mixture via syringe
  4. customThe solution was sealed
  5. temperatureto cool to room temperature
  6. washwashed with aqueous sodium bicarbonate and brine
  7. customThe organic layers were collected
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification
  12. additionFractions containing product
  13. concentrationwere concentrated under reduced pressure
  14. custommethanol, and recrystallized out

Sources & evidence

ORD record
ord-f03fec0f40f141369261ae6a7113a1a0
Source dataset
uspto-grants-2013_04
Patent number
US08420695B2

Reaction notes

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