Methyl iodide → 3-Bromo-6-methoxypyridin-2-amine

HRID 1848362Notes

Reaction equation

HRID 1848362 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[Br:9].[C:10]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[Br:9][C:3]1[C:2]([NH2:1])=[N:7][C:6]([O:8][CH3:10])=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 178508959HCID 178508959, compound

Product 1

HCID 234358793-Bromo-6-methoxypyridin-2-amineYield 12.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under an argon atmosphere 6-amino-5-bromo-pyridin-2-ol (23 g, 122 mmol) was dissolved in DMF (300 mL). K2CO3 (50.6 g, 366 mmol) was added followed by the addition of methyl iodide (11.4 mL, 183 mmol). The mixture was stirred for 4 h while keeping the temperature at 20-25° C. The suspension was poured onto H2O (1 L) and the aqueous phase was extracted with EtOAc (×2). The combined organic phases washed with H2O (0.5 L) and brine (200 mL), dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography, eluent toluene:heptane 2:1->100:0 followed by toluene:EtOAc 95:5 to afford 3-bromo-6-methoxy-pyridin-2-ylamine as a solid (3 g).

Workup

  1. customat 20-25° C
  2. additionThe suspension was poured onto H2O (1 L)
  3. extractionthe aqueous phase was extracted with EtOAc (×2)
  4. washThe combined organic phases washed with H2O (0.5 L) and brine (200 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography, eluent toluene:heptane 2:1->100:0

Sources & evidence

ORD record
ord-c770a1b1092a44f2bb4fce3b0585347d
Source dataset
uspto-grants-2015_02
Patent number
US08952162B2

Reaction notes

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