Potassium Carbonate → HCID 58256467, compound

HRID 1967160Notes

Reaction equation

HRID 1967160 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].Br[C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[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]>[F:16][C:15]1[CH:14]=[C:13]([C:17]([OH:20])([CH3:18])[CH3:19])[CH:12]=[C:11]([F:21])[C:10]=1[C:4]1[S:3][C:2]([NH:1][C:23]2[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=2)=[C:6]([C:7]([NH2:9])=[O:8])[CH:5]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 707414-BromobenzaldehydeHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 595256192-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

Product 1

HCID 58256467HCID 58256467, 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 (750 mg, 2.401 mmol) and 4-bromobenzaldehyde (444 mg, 2.401 mmol), Pd2(dba)3 (220 mg, 0.240 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (572 mg, 1.201 mmol), and potassium carbonate (365 mg, 2.64 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed tert-amyl alcohol (8 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 and taken up in ethyl acetate. The suspension was washed in aqueous sodium bicarbonate twice and brine twice, and the organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification was performed via silica gel chromatography (0-3% methanol in ethyl acetate).

Workup

  1. additionA sealed tube was charged with a stir bar
  2. customThe tube was evacuated
  3. additionFully degassed tert-amyl alcohol (8 mL) was added to the mixture via syringe
  4. customThe solution was sealed
  5. temperatureto cool to room temperature
  6. washThe suspension was washed in aqueous sodium bicarbonate twice
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification

Sources & evidence

ORD record
ord-c0da27d8ba054babbc34cc205682459a
Source dataset
uspto-grants-2013_04
Patent number
US08420695B2

Reaction notes

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