3,4-Dimethoxyaniline → 5-[(3,4-Dimethoxy-phenylamino)-methylsulfanyl-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dione

HRID 563033Notes

Reaction equation

HRID 563033 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=C(SC)C=C2OC1C=CC(NC(C2(C(NC3C=CC(F)=CC=3)=O)CC2)=O)=CC=1F.CS[C:43]([S:54][CH3:55])=[C:44]1[C:49](=[O:50])[O:48][C:47]([CH3:52])([CH3:51])[O:46][C:45]1=[O:53].COC1C=C(C=CC=1OC)N>CCO>[CH3:14][O:13][C:12]1[CH:11]=[C:10]([NH:9][C:43]([S:54][CH3:55])=[C:44]2[C:49](=[O:50])[O:48][C:47]([CH3:52])([CH3:51])[O:46][C:45]2=[O:53])[CH:5]=[CH:4][C:3]=1[O:2][CH3:1]

Participants

5

Reactant 3

HCID 227703,4-DimethoxyanilineHCID 17451285-[Bis(methylsulfanyl)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dioneHCID 57810395N-(4-{[6,7-bis(methyloxy)-2-(methylthio)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluoro-phenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 578100945-[(3,4-Dimethoxy-phenylamino)-methylsulfanyl-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dioneYield 83%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Synthesis of N-(4-{[6,7-bis(methyloxy)-2-(methylthio)quinolin-4-yl]oxy}-3-fluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Commercially available 5-(bis-methylsulfanyl-methylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione (3.5 g, 14 mmol) and 3,4-dimethoxyaniline (2.2 g, 14 mmol) were reflux in EtOH (20 mL) for 2 hours. The EtOH was removed under reduced pressure and EtOAc was added to the residue. The product was filtered and washed with cold EtOAc (3×). 5-[(3,4-dimethoxy-phenylamino)-methylsulfanyl-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dione was obtained as a white solid (1.7 g, 47% yield) and used without further purification. LCMS: m/z 352 (M−H)−.

Workup

  1. customThe EtOH was removed under reduced pressure and EtOAc
  2. additionwas added to the residue
  3. filtrationThe product was filtered
  4. washwashed with cold EtOAc (3×)

Sources & evidence

ORD record
ord-47b38e14f570414e93add3628ab1fad3
Source dataset
uspto-grants-2011_11
Patent number
US08067436B2

Reaction notes

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