Methanamine, N-methoxy-, hydrochloride (1:1) → 5-Bromo-N-methoxy-N-methylpicolinamide

HRID 510989Notes

Reaction equation

HRID 510989 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[Br:39][C:40]1[CH:41]=[CH:42][C:43]([C:46]([OH:48])=O)=[N:44][CH:45]=1>CN(C=O)C>[Br:39][C:40]1[CH:41]=[CH:42][C:43]([C:46]([N:3]([O:4][CH3:5])[CH3:2])=[O:48])=[N:44][CH:45]=1

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 6085445-Bromopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 629527015-Bromo-N-methoxy-N-methylpicolinamideYield 102%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,O-dimethylhydroxylamine hydrochloride (500 mg, 5 mmol) was added to a mixture of N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (1400 mg, 3.7 mmol), DIPEA (1000 μL, 7 mmol) and 5-bromopyridine-2-carboxylic acid (500 mg, 2 mmol, Frontier Scientific catalog# B1704) in DMF (10 mL) at room temperature. The reaction was stirred overnight and was partitioned between water and EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give the crude product. The product was purified by chromatography on silica gel eluting with a hexane:EtOAc gradient to give 5-bromo-N-methoxy-N-methylpyridine-2-carboxamide as a clear oil (0.5 g, 60%). LCMS calculated for C8H10BrN2O2(M+H)+: m/z=244.9, 246.9. found: 244.9, 246.9.

Workup

  1. customwas partitioned between water and EtOAc
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customThe product was purified by chromatography on silica gel eluting with a hexane

Sources & evidence

ORD record
ord-8c634effbfbb4e7584709a87af167c5b
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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