Potassium Carbonate → HCID 89837029, compound

HRID 1054815Notes

Reaction equation

HRID 1054815 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][N:6]=[C:5]2[C:12]([OH:14])=[O:13].CC1(C)C(C)(C)OB([C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][OH:31])=[CH:25][CH:24]=2)O1.C(=O)([O-])[O-].[K+].[K+]>CCO.C1(C)C=CC=CC=1.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]>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([C:12]([OH:14])=[O:13])=[N:6][NH:7]2)=[CH:3][C:2]=1[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][OH:31])=[CH:25][CH:24]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 597918422-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethan-1-olHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acid

Product 1

HCID 89837029HCID 89837029, compoundYield 13.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (75 mg, 0.27 mmol), 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol (75 mg, 0.30 mmol) in EtOH (0.5 mL) and toluene (0.5 mL) was added 2 N aqueous potassium carbonate solution (0.5 mL, 1.0 mmol). The reaction mixture was degassed with N2 for 5 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (11.4 mg, 0.014 mmol) and degassed with N2 for another 5 minutes. The suspension was sealed in a pressure tube and heated to 130° C. for 1 hour. As the reaction progressed, the suspension became clear, turned to orange and then dark brown. The reaction mixture was diluted with EtOAc (5 mL) and water (5 mL), and filtered through a syringe filter. The aqueous layer was acidified to pH 5 by 1 N HCl solution, and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% Formic acid in water (v/v); Mobile phase B: 0.05% Formic acid in MeCN (v/v); HOLD at 80.0% H2O/20.0% MeCN for 1.0 min. 80.0% H2O/20.0% MeCN linear to 60.0% H2O/40.0% MeCN in 6.75 min, linear to 0% H2O/100% MeCN to 7.0 min. HOLD at 0% H2O/100% MeCN from 7.0 to 8.0 min. Flow: 30 mL/min) to provide the title compound (11.5 mg, 13% yield). MS (ES+) 317.1 (M+H)+. Retention time=2.27 minutes (Column: Waters Atlantis dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Workup

  1. customThe reaction mixture was degassed with N2 for 5 minutes
  2. customdegassed with N2 for another 5 minutes
  3. customThe suspension was sealed in a pressure tube
  4. additionThe reaction mixture was diluted with EtOAc (5 mL) and water (5 mL)
  5. filtrationfiltered through a syringe
  6. filtrationfilter
  7. extractionextracted with EtOAc
  8. dry with materialThe organic layer was dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% Formic acid in water (v/v); Mobile phase B: 0.05% Formic acid in MeCN (v/v); HOLD at 80.0% H2O/20.0% MeCN for 1.0 min. 80.0% H2O/20.0% MeCN linear to 60.0% H2O/40.0% MeCN in 6.75 min, linear to 0% H2O/100% MeCN to 7.0 min. HOLD at 0% H2O/100% MeCN from 7.0 to 8.0 min. Flow: 30 mL/min)

Sources & evidence

ORD record
ord-4bc5d27567d64129998cf0edc4e7b3d9
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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