Triethylamine → 1-(4-Bromo-2,5-difluorophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide

HRID 1895224Notes

Reaction equation

HRID 1895224 reaction equation
[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]([OH:20])=O)=[N:10]2)=[C:4]([F:21])[CH:3]=1.Cl.[CH3:23][NH:24][O:25][CH3:26].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C>CN(C=O)C.CCOC(C)=O.CCOC(C)=O.CO>[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]([N:24]([O:25][CH3:26])[CH3:23])=[O:20])=[N:10]2)=[C:4]([F:21])[CH:3]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 580723251-(4-Bromo-2,5-difluorophenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylic acid

Product 1

HCID 580723461-(4-Bromo-2,5-difluorophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideYield 32.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

A mixture of 1-(4-bromo-2,5-difluorophenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylic acid (25 g, 83 mmol), N,O-dimethylhydroxylamine hydrochloride (8.9 g, 91 mmol), HOBt (12 g, 91 mmol), triethylamine (24 mL, 174 mmol) and WSC (17 g, 91 mmol) in DMF (160 mL) was stirred at room temperature for 18 h. The mixture was diluted with AcOEt, washed with water and brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with Hexane/AcOEt (1/0 to 0/1) and then AcOEt/MeOH (10/1) to give the title compound (11 g, 31% yield) as a yellow solid: LC-MS (ESI) m/z 405 [M+H]+.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography
  5. washeluting with Hexane/AcOEt (1/0 to 0/1)

Sources & evidence

ORD record
ord-a7d2b01cd374454a814cf033fa7ca742
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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