Sodium Carbonate → 5-(2-(4-Fluorophenyl)-5-(pyridin-4-yl)oxazol-4-yl)-3-methoxypyridin-2-amine

HRID 538419Notes

Reaction equation

HRID 538419 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.Br[C:11]1[O:15][C:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:13][C:12]=1[C:23]1[CH:24]=[C:25]([O:30][CH3:31])[C:26]([NH2:29])=[N:27][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:14]2[O:15][C:11]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)=[C:12]([C:23]3[CH:24]=[C:25]([O:30][CH3:31])[C:26]([NH2:29])=[N:27][CH:28]=3)[N:13]=2)=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 665911705-(5-Bromo-2-(4-fluorophenyl)oxazol-4-yl)-3-methoxypyridin-2-amine

Product 1

HCID 591372935-(2-(4-Fluorophenyl)-5-(pyridin-4-yl)oxazol-4-yl)-3-methoxypyridin-2-amineYield 56.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 4-pyridineboronic acid (113 mg, 0.9 mmol) and 5-(5-bromo-2-(4-fluorophenyl)oxazol-4-yl)-3-methoxypyridin-2-amine (135 mg, 0.4 mmol), and in DME (1.0 mL) and 2.0 M aqueous Na2CO3 (1.0 mL, 2.0 mmol) was sparged with Ar. Tetrakis(triphenylphosphine)palladium(0) (21 mg, 0.018 mmol) was added and the mixture was again sparged with Ar. The reaction was irradiated at 120° C. for 15 min in a microwave reactor. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography over (SiO2, 100:0-0:100 hexanes-EtOAc). Enriched fractions were concentrated in vacuo and further purified by column chromatography (SiO2, 100:0-80:20 DCM-MeOH) to afford 82 mg of the title compound: LC/MS (m/z): 362.9 (MH+), tR=0.54 min.

Workup

  1. customthe mixture was again sparged with Ar
  2. customThe reaction was irradiated at 120° C. for 15 min in a microwave reactor
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography over (SiO2, 100:0-0:100 hexanes-EtOAc)
  9. concentrationEnriched fractions were concentrated in vacuo
  10. customfurther purified by column chromatography (SiO2, 100:0-80:20 DCM-MeOH)

Sources & evidence

ORD record
ord-8453313e9225479283b551328cf2741f
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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