1-Hydroxybenzotriazole → 2-Bromo-N-methoxy-N-methylisonicotinamide

HRID 1667615Notes

Reaction equation

HRID 1667615 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][N:3]=1.C1C=CC2N(O)N=NC=2C=1.CN([C:24]([O:28][N:29]1N=NC2C=CC=C[C:30]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.CNOC.C(N(C(C)C)CC)(C)C>CS(C)=O.O>[Br:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][N:3]=1)[C:8]([N:29]([O:28][CH3:24])[CH3:30])=[O:10]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 2227012-Bromoisonicotinic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 448186542-Bromo-N-methoxy-N-methylisonicotinamideYield 86.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 2-bromo-pyridine-4-carboxylic acid (11.83 g, 58.56 mmol) in DMSO (100 mL) are added HOBt (9.49 g, 70.30 mmol) and HBTU (26.70 g, 70.30 mmol). The mixture is stirred at room temperature for 20 min, then N,O-dimethylhydroxylamine HCl (6.28 g, 64.41 mmol) and diisopropylethylamine (22.72 g, 175.68 mmol) are added to the mixture. After stirring at room temperature for 3 h, the reaction mixture is diluted with water and extracted with EtOAc. The combined organic layers are washed with water, sat. NaHCO3, brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 10%˜40%) to give 2-Bromo-N-methoxy-N-methyl-isonicotinamide (12.4 g, 86%) as a white solid. M/Z=245.0

Workup

  1. stirringAfter stirring at room temperature for 3 h
  2. extractionextracted with EtOAc
  3. washThe combined organic layers are washed with water, sat. NaHCO3, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated down
  7. customThe crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 10%˜40%)

Sources & evidence

ORD record
ord-e5e378ea00c64b4ca1008cbdc0e4d3ca
Source dataset
uspto-grants-2011_10
Patent number
US08044209B2

Reaction notes

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