Potassium Carbonate → HCID 89837014, compound

HRID 1054840Notes

Reaction equation

HRID 1054840 reaction equation
CC1(C)COB([C:8]2[CH:13]=[CH:12][C:11]([C:14]3([OH:18])[CH2:17][CH2:16][CH2:15]3)=[C:10]([O:19][CH3:20])[CH:9]=2)OC1.Br[C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][C:31]=1[Cl:32])[NH:28][N:27]=[C:26]2[C:33]([OH:35])=[O:34].C(=O)([O-])[O-].[K+].[K+].OS([O-])(=O)=O.[Na+]>C(OCC)(=O)C.CS(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCO.C1COCC1.C1(C)C=CC=CC=1>[Cl:32][C:31]1[CH:30]=[C:29]2[C:25]([C:26]([C:33]([OH:35])=[O:34])=[N:27][NH:28]2)=[CH:24][C:23]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2([OH:18])[CH2:15][CH2:16][CH2:17]2)=[C:10]([O:19][CH3:20])[CH:9]=1

Participants

11

Reactant 4

HCID 11430Potassium CarbonateHCID 516919Sodium BisulfateHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acidHCID 89837023HCID 89837023, compound

Product 1

HCID 89837014HCID 89837014, compoundYield 12.6%

Reagents, catalysts & solvents 6

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

A sealed tube was charged with 1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-methoxyphenyl]cyclobutanol (50 mg, 0.17 mmol), 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (47.4 mg, 0.172 mmol), toluene (0.80 mL), THF (0.40 mL), EtOH (0.40 mL), and 2 M potassium carbonate (0.40 mL, 0.80 mmol). Nitrogen was then bubbled through the mixture for 5 minutes. [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (14.6 mg, 0.017 mmol) was added and the tube sealed and heated to 115° C. for 2 hours. The reaction was cooled to room temperature, opened, neutralized with 1 M NaHSO4, and diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate (×2). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to provide the crude material (80 mg). 40 mg was dissolved in DMSO and subjected to reverse phase chromatography to provide 8 mg (10% yield) of title compound.

Workup

  1. customNitrogen was then bubbled through the mixture for 5 minutes
  2. customthe tube sealed
  3. temperatureThe reaction was cooled to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (×2)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide the crude material (80 mg)

Sources & evidence

ORD record
ord-360c8670f6724a42bed24c2fbb5ceff0
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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