Triethylamine → 5-bromo-3-fluoro-N-methoxy-N-methylpyridine-2-carboxamide

HRID 1374168Notes

Reaction equation

HRID 1374168 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([F:11])[C:5]([C:8](O)=[O:9])=[N:6][CH:7]=1.Cl.[CH3:13][O:14][NH:15][CH3:16].ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([F:11])[C:5]([C:8]([N:15]([O:14][CH3:13])[CH3:16])=[O:9])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 181649HOAtHCID 210758725-Bromo-3-fluoropyridine-2-carboxylic acid

Product 1

HCID 210758695-bromo-3-fluoro-N-methoxy-N-methylpyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of crude 5-bromo-3-fluoropyridine-2-carboxylic acid (40.65 g, 184.8 mmol), O,N-dimethylhydroxylamine hydrochloride (21.63 g, 221.7 mmol), 1-ethyl-(3-dimethyl-aminopropyl)-carbodiimide hydrochloride (70.85 g, 369.6 mmol), 1-hydroxy-7-azabenzotriazole (2.497 g, 18.48 mmol), and triethylamine (16.48 mL, 118.3 mmol) in 200 mL DMF was stirred at room temperature overnight. The solution was partially concentrated in vacuo and partitioned between ethyl acetate and 10% aqueous sodium bicarbonate. The aqueous layer was extracted 4× with ethyl acetate, and the combined organics were washed with water and brine, dried over Na2SO4, filtered and concentrated under vacuum to provide 5-bromo-3-fluoro-N-methoxy-N-methylpyridine-2-carboxamide that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 263.01 for M+H+(79Br).

Workup

  1. concentrationThe solution was partially concentrated in vacuo
  2. custompartitioned between ethyl acetate and 10% aqueous sodium bicarbonate
  3. extractionThe aqueous layer was extracted 4× with ethyl acetate
  4. washthe combined organics were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-1c16b7dd319748288a7b04a8f4712977
Source dataset
uspto-grants-2007_01
Patent number
US07163951B2

Reaction notes

Loading…