Potassium Carbonate → HCID 86698823, compound

HRID 338488Notes

Reaction equation

HRID 338488 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].[CH3:15][O:16][CH:17]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)[CH3:18].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO>[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:22]1[CH:23]=[CH:24][C:19]([CH:17]([O:16][CH3:15])[CH3:18])=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 45791053[4-(1-Methoxyethyl)phenyl]boronic acidHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acid

Product 1

HCID 86698823HCID 86698823, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (40.0 mg, 0.14 mmol), 4-(1-methoxyethyl)phenylboronic acid (27.4 mg, 0.152 mmol) and 2N aqueous potassium carbonate solution (0.2 mL, 0.4 mmol) in toluene (0.3 mL) and EtOH (0.7 mL) was purged with N2, and treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) under N2. The reaction mixture was heated to 100° C. for 48 hours, cooled to room temperature 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% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 0% H2O/100% MeCN in 7.0 min, HOLD at 0% H2O/100% MeCN to 8.5 min. Flow: 25 mL/min) to afford the title compound (4.9 mg, 11% yield). MS (ES+) 331.1 (M+H)+. Retention time=2.71 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. customwas purged with N2
  2. additiontreated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) under N2
  3. temperaturecooled to room temperature
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 0% H2O/100% MeCN in 7.0 min, HOLD at 0% H2O/100% MeCN to 8.5 min. Flow: 25 mL/min)

Sources & evidence

ORD record
ord-a8056a4b03734c9395022e8c9e7f6110
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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