5-Bromo-4,6-dimethylpyridin-3-amine → 4-bromo-5-methyl-1H-pyrazolo[3,4-c]pyridine

HRID 468834Notes

Reaction equation

HRID 468834 reaction equation
[Br:1][C:2]1[C:3]([CH3:10])=[C:4]([NH2:9])[CH:5]=[N:6][C:7]=1[CH3:8].[N:11]([O-])=O.[Na+]>C(O)(=O)C>[Br:1][C:2]1[C:7]([CH3:8])=[N:6][CH:5]=[C:4]2[NH:9][N:11]=[CH:10][C:3]=12

Participants

4

Reactant 2

HCID 70606665-Bromo-4,6-dimethylpyridin-3-amineHCID 23668193Sodium Nitrite

Product 1

HCID 679764014-bromo-5-methyl-1H-pyrazolo[3,4-c]pyridineYield 53%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-bromo-4,6-dimethylpyridin-3-amine (1.00 g, 4.98 mmol) in acetic acid (12 mL) at ambient temperature was added sodium nitrite (364 mg, 5.28 mmol) and the mixture heated to 60° C. for 1.5 hr. The cooled reaction mixture was concentrated in vacuo, the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate and the biphasic mixture filtered through a celite pad. The separated aqueous phase was extracted with ethyl acetate, and the combined organic phases washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica, ISCO, 10-100% ethyl acetate in heptane) to afford the title compound as a pale brown solid (554 mg, 53%). 1H NMR (300 MHz, DMSO) δ 13.91 (s, 1H), 8.95 (s, 1H), 8.14 (s, 1H), 2.67 (s, 3H). LCMS: M+H+=212 & 214.

Workup

  1. customThe cooled reaction mixture
  2. concentrationwas concentrated in vacuo
  3. customthe residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  4. filtrationthe biphasic mixture filtered through a celite pad
  5. extractionThe separated aqueous phase was extracted with ethyl acetate
  6. washthe combined organic phases washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (silica, ISCO, 10-100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-91e9980f10d642c886f5588c0a7115ff
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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