2-Methoxypyrimidine-5-boronic acid → HCID 59569599, compound

HRID 217592

Reaction equation

HRID 217592 reaction equation
[NH2:1][C:2]1[C:3]([F:21])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17](I)[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1.[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27](B(O)O)=[CH:26][N:25]=1>C(=O)([O-])[O-].[K+].[K+].O.C(#N)C.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]>[NH2:1][C:2]1[C:3]([F:21])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:27]4[CH:26]=[N:25][C:24]([O:23][CH3:22])=[N:29][CH:28]=4)[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1

Participants

7

Reactant 2

HCID 27367782-Methoxypyrimidine-5-boronic acidHCID 58368852HCID 58368852, compound

Product 1

HCID 59569599HCID 59569599, compoundYield 43.6%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
160 °C

Procedure

In a microwave vial, (3-amino-2,6-difluoro-phenyl)-(5-iodo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (19, 1.36 g, 3.41 mmol), 2-methoxy-pyrimidine-5-boronic acid (20, 1.05 g, 6.81 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.25 g, 0.34 mmol) were mixed in 22 mL of 1.00 M potassium carbonate in water and 18 mL of acetonitrile. The resulting mixture was heated at 160° C. in the microwave for 15 minutes. The resulting mixture was filtered through a thin layer of celite, and the celite bed was washed with a mixture of water and ethyl acetate. The two layers of the filtrate were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and the filtrate concentrated under vacuum. The residue was purified by flash silica gel chromatography eluting with ethyl acetate and dichloromethane to provide the desired compound (21, 0.567 g). MS (ESI) [M+H+]+=382.1.

Workup

  1. filtrationThe resulting mixture was filtered through a thin layer of celite, and the celite bed
  2. washwas washed with a mixture of water and ethyl acetate
  3. customThe two layers of the filtrate were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under vacuum
  9. customThe residue was purified by flash silica gel chromatography
  10. washeluting with ethyl acetate and dichloromethane

Sources & evidence

ORD record
ord-0fe67580fcf141079f561e1207acb3e2
Source dataset
uspto-grants-2012_06
Patent number
US08198273B2

Linked notes

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