Potassium Carbonate → HCID 44465600, compound

HRID 241606Notes

Reaction equation

HRID 241606 reaction equation
Br[C:2]1[N:3]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[C:4]2[C:9]([C:10]=1[C:11]#[N:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.[S:20]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21]1.C(=O)([O-])[O-].[K+].[K+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1COCC1.CCO.O>[OH:19][C:16]1[CH:17]=[CH:18][C:13]([N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]([C:11]#[N:12])=[C:2]2[C:22]2[CH:23]=[CH:24][S:20][CH:21]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 581760Thiophene-3-boronic acidHCID 44241532HCID 44241532, compound

Product 1

HCID 44465600HCID 44465600, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 18504229Ethanol tetrahydrofuran waterSolvent

Conditions

Temperature
100 °C

Procedure

To 2-bromo-1-(4-hydroxy-phenyl)-1H-indole-3-carbonitrile (Example 1) was added 2 eq 3-thiopheneboronic acid, 2.1 eq potassium carbonate and 10 mol % tetrakis(triphenylphosphine) palladium. THF:EtOH:H2O (4:1:0.5) was added and the vial was flushed with nitrogen, sealed and stirred at 100° C. for 48 hours. The reaction mixture was cooled to rt, diluted with H2O, extracted with EtOAc and filtered through silica. The organic phase was evaporated to dryness and the crude product was subjected to reversed phase preparative HPLC. Appropriate fractions were combined, evaporated, and identified by 1H-NMR and LC/MS. Purity was determined by analytical HPLC. ES/MS m/z: 317.9 (M+H), 314.8 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.73 (m, 1H), 7.62 (dd, 1H, J=1.3, 2.9 Hz), 7.54 (dd, 1H, J=2.9, 5.0 Hz), 7.37-7.30 (m, 2H), 7.26 (m, 2H), 7.18 (m, 1H), 7.15 (dd, 1H, J=1.3, 5.0 Hz) and 7.03 (m, 2H).

Workup

  1. customthe vial was flushed with nitrogen
  2. customsealed
  3. temperatureThe reaction mixture was cooled to rt
  4. additiondiluted with H2O
  5. extractionextracted with EtOAc
  6. filtrationfiltered through silica
  7. customThe organic phase was evaporated to dryness
  8. customevaporated

Sources & evidence

ORD record
ord-47dc6e348adb4bca9a956f987934c930
Source dataset
uspto-grants-2014_02
Patent number
US08653072B2

Reaction notes

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