Potassium Carbonate → HCID 59334627, compound

HRID 1639866Notes

Reaction equation

HRID 1639866 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:11])[N:7]=2)[C:3]=1[CH:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:19])[CH3:18].[CH2:20](B(O)O)[CH3:21].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+]>C(OCC)(=O)C.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].CN(C)C=O>[CH2:20]([C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:11])[N:7]=2)[C:3]=1[CH:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH3:21]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 521157Ethylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59334491HCID 59334491, compound

Product 1

HCID 59334627HCID 59334627, compoundYield 18.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

N-{[2-(5-Bromo-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl}acetamide (200 mg, 0.621 mmol) obtained in Example 29, ethylboronic acid (229 mg, 3.105 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (30.0 mg, 0.0621 mmol), potassium carbonate (206 mg, 1.49 mmol) and tris(dibenzylideneacetone)dipalladium(0) (29.3 mg, 0.0311 mmol) were added to N,N-dimethylformamide (3.1 mL), and the mixture was stirred under nitrogen atmosphere with heating at 120° C. for 1 day. The reaction solution was diluted with ethyl acetate, and filtered through celite. The obtained filtrate was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate=0/100→5/95), silica gel column chromatography (NH, methanol/ethyl acetate=0/100→20/80) and HPLC to give the title compound (31 mg, yield 18%).

Workup

  1. filtrationfiltered through celite
  2. washThe obtained filtrate was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate=0/100→5/95), silica gel column chromatography (NH, methanol/ethyl acetate=0/100→20/80) and HPLC

Sources & evidence

ORD record
ord-e4df7f89784f4753bcb190d243ad5c90
Source dataset
uspto-grants-2012_02
Patent number
US08110585B2

Reaction notes

Loading…