Potassium Carbonate → HCID 86698809, compound

HRID 338473Notes

Reaction equation

HRID 338473 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].[OH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.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:20]1[CH:21]=[CH:22][C:17]([CH2:16][OH:15])=[CH:18][CH:19]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acid

Product 1

HCID 86698809HCID 86698809, compoundYield 15.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

A mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (200.0 mg, 0.73 mmol), 4-(hydroxymethyl)phenylboronic acid (90.0 mg, 0.59 mmol), 2N aqueous potassium carbonate (1.1 mL, 2.2 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (60.0 mg, 0.073 mmol) in toluene (1.5 mL) and EtOH (2.3 mL) was degassed with N2 for 3 minutes and heated to 110° C. for 5 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was acidified to pH 5 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Phenomenex Synergi C18 150×30 mm, 4 μm; 28% MeCN in water (0.225% TFA) to 28% MeCN in water (0.225% TFA) for 12 min; Flow Rate: 30 mL/min) to afford the title compound (27 mg, 11% yield) as a white solid. MS (ES+) 302.9 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.11 (s, 1H), 7.76 (s, 1H), 7.45 (m, 4H), 4.69 (s, 2H).

Workup

  1. customwas degassed with N2 for 3 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by reverse phase HPLC (Column: Phenomenex Synergi C18 150×30 mm, 4 μm; 28% MeCN in water (0.225% TFA) to 28% MeCN in water (0.225% TFA) for 12 min; Flow Rate: 30 mL/min)

Sources & evidence

ORD record
ord-1f480bec000b4bfbac2d6fa9c70ff36a
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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