Ethylacetate methanol → Methyl 1-(4-bromo-2,5-difluorophenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylate

HRID 2089881Notes

Reaction equation

HRID 2089881 reaction equation
[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([NH:9][N:10]=[C:11]([C:16](=[O:20])[CH2:17][O:18][CH3:19])[C:12]([O:14][CH3:15])=[O:13])=[C:4]([F:21])[CH:3]=1.[CH3:22]COC(C)=O.CO>COC(OC)N(C)C>[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([N:9]2[CH:22]=[C:17]([O:18][CH3:19])[C:16](=[O:20])[C:11]([C:12]([O:14][CH3:15])=[O:13])=[N:10]2)=[C:4]([F:21])[CH:3]=1

Participants

4

Reactant 2

HCID 21584119Ethylacetate methanolHCID 178496284methyl 2-[(4-bromo-2,5-difluorophenyl)hydrazinylidene]-4-methoxy-3-oxobutanoate

Product 1

HCID 58072213Methyl 1-(4-bromo-2,5-difluorophenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylateYield 83%

Reagents, catalysts & solvents 1

HCID 78373Dimethylformamide dimethyl acetalSolvent

Procedure

A solution of methyl 2-[(4-bromo-2,5-difluorophenyl)hydrazono]-4-methoxy-3-oxobutanoate (33 g, 90 mmol) in N,N-dimethylformamide dimethyl acetal (72 mL) was stirred at 110° C. for 3 h. After cooling to room temperature, the mixture was concentrated under reduce pressure. To the residue were added MeOH and silica gel. The mixture was evaporated and purified by silica gel column chromatography eluting with hexane/AcOEt (1/0 to 0/1) and then AcOEt/MeOH (4/1) to give the title compound (27.9 g, 83% yield) as a brown gum: NMR (300 MHz, DMSO-d5): δ ppm 3.80 (3H, s), 3.83 (3H, s), 8.01 (1H, dd, J=8.7, 6.8 Hz), 8.15 (1H, dd, J=9.8, 6.0 Hz), 8.55 (1H, d, J=1.5 Hz). LC-MS (ESI) m/z 376 [M+H]+.

Workup

  1. concentrationthe mixture was concentrated
  2. additionTo the residue were added MeOH and silica gel
  3. customThe mixture was evaporated
  4. custompurified by silica gel column chromatography
  5. washeluting with hexane/AcOEt (1/0 to 0/1)

Sources & evidence

ORD record
ord-c4002249177943109fc12040ee5943e4
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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