Potassium Carbonate → HCID 46203393, compound

HRID 1662274Notes

Reaction equation

HRID 1662274 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=3)[C:16]3[C:11](=[C:12]([F:18])[CH:13]=[C:14]([Cl:17])[CH:15]=3)[C:10]([NH2:19])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[N:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[N:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.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:17][C:14]1[CH:15]=[C:16]2[C:11]([C:10]([NH2:19])=[N:9][C:8]2([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=2)[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:31]3[CH:32]=[N:27][CH:28]=[N:29][CH:30]=3)[CH:3]=2)=[C:12]([F:18])[CH:13]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 58579493HCID 58579493, compound

Product 1

HCID 46203393HCID 46203393, compoundYield 31.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

1-(3-Bromophenyl)-6-chloro-4-fluoro-1-(2-methylpyridin-4-yl)-1H-isoindol-3-amine (1 g, 2.32 mmol), pyrimidine-5-boronic acid (0.316 g, 2.55 mmol) and [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (0.096 g, 0.12 mmol) were dissolved in DMF (10 mL) and heated to 90° C. Then aqueous potassium carbonate (3.48 mL, 6.97 mmol) was added and the resulting mixture was stirred at 120° C. for 2 h. When cooled to rt the mixture was diluted with water (50 mL) and extracted with DCM (3×50 mL). The combined organics were washed with water (75 mL), passed through a phase separator, concentrated and purified on a silica gel column eluted with 0-10% 0.1M NH3 in MeOH in DCM to afford 310 mg (31% yield) of the title compound.

Workup

  1. temperatureWhen cooled to rt the mixture
  2. extractionextracted with DCM (3×50 mL)
  3. washThe combined organics were washed with water (75 mL)
  4. concentrationconcentrated
  5. custompurified on a silica gel column
  6. washeluted with 0-10% 0.1M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-13a87e0ebd96414bad768e2617c0a12c
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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