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

HRID 2089883Notes

Reaction equation

HRID 2089883 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 31%

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-0573391d63234b828874db2286406c9a
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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