Dimethylformamide → 6-Methoxy-5-methyl-3-nitro-2-pyridineamine

HRID 505392Notes

Reaction equation

HRID 505392 reaction equation
I[C:2]1[CH:3]=[C:4]([N+:11]([O-:13])=[O:12])[C:5]([NH2:10])=[N:6][C:7]=1[O:8][CH3:9].[CH3:14]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>C(OCC)(=O)C.O.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>[CH3:9][O:8][C:7]1[N:6]=[C:5]([NH2:10])[C:4]([N+:11]([O-:13])=[O:12])=[CH:3][C:2]=1[CH3:14]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 574072Trimethylboroxine2×HCID 573549285-Iodo-6-methoxy-3-nitropyridin-2-amine

Product 1

HCID 552528376-Methoxy-5-methyl-3-nitro-2-pyridineamineYield 54.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-iodo-6-methoxy-3-nitro-2-pyridineamine (1.03 g, 3.49 mmol), trimethylboroxin (456 mg, 3.63 mmol), cesium carbonate (3.56 g, 10.9 mmol), tetrakis(triphenylphosphine)palladium(0) (412 mg, 0.357 mmol) and N,N-dimethylformamide (10 ml) was stirred at 90° C. under nitrogen atmosphere. After 2 hours and 30 minutes, trimethylboroxin (500 μl, 3.58 mmol) was added, and the reaction mixture was further stirred under the same conditions for 5 hours and 30 minutes. The reaction mixture was cooled to room temperature and then diluted with ethyl acetate and water. Insoluble substance was filtered off, the organic layer of the filtrate was washed 3 times with a saturation ammonium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (silica gel: 40 g, eluting solvent: heptane, heptane/ethyl acetate=90/10) to yield the title compound (350 mg, 1.91 mmol, 54.8%) as a yellow solid.

Workup

  1. stirringthe reaction mixture was further stirred under the same conditions for 5 hours and 30 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationInsoluble substance was filtered off
  4. washthe organic layer of the filtrate was washed 3 times with a saturation ammonium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (silica gel: 40 g, eluting solvent: heptane, heptane/ethyl acetate=90/10)

Sources & evidence

ORD record
ord-21b82de0329047d6a0fc9a8506a13f03
Source dataset
uspto-grants-2010_08
Patent number
US07781452B2

Reaction notes

Loading…