Acetonitrile → HCID 86698810, compound

HRID 338474Notes

Reaction equation

HRID 338474 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][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CC#N>C1(C)C=CC=CC=1.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]>[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:19]=[CH:18][CH:17]=[C:16]([OH:15])[CH:21]=1

Participants

8

Reactant 4

HCID 6342Acetonitrile2×HCID 11430Potassium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acid

Product 1

HCID 86698810HCID 86698810, compoundYield 4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent3×HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (100 mg, 0.36 mmol), 3-hydroxyphenylboronic acid (51.0 mg, 0.36 mmol), potassium carbonate (301 mg, 2.18 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (30.0 mg, 0.036 mmol) in toluene (1.5 mL) and water (1.1 mL) was degassed with N2 for 3 minutes and heated to 110° C. for 16 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. The brown residue was acidified to pH 4 with 1N HCl and extracted with n-butanol (3×20 mL). The combined organic layers were washed with brine (2×20 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Phenomenex Synergi C18 150×30 mm, 4 μm; 25% MeCN in water (0.225% TFA) to 45% MeCN in water (0.225% TFA) to afford the title compound (4 mg, 4% yield) as a white solid.

Workup

  1. customwas degassed with N2 for 3 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. extractionextracted with n-butanol (3×20 mL)
  5. washThe combined organic layers were washed with brine (2×20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by reverse phase HPLC (Column

Sources & evidence

ORD record
ord-1599bbb1d03e4059b72263ae36562f7f
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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