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

HRID 563038Notes

Reaction equation

HRID 563038 reaction equation
FC1C=C(NC(C2(C(NC3C=CC(F)=CC=3)=O)CC2)=O)C=CC=1OC1C2C(=CC(OC)=C(OC)C=2)[N:12]=[C:11](NC)C=1.[CH3:41][O:42][C:43]1[CH:44]=[C:45]([NH:51][C:52](SC)=[C:53]2[C:58](=[O:59])[O:57][C:56]([CH3:61])([CH3:60])[O:55][C:54]2=[O:62])[CH:46]=[CH:47][C:48]=1[O:49][CH3:50].CN>C1COCC1.Cl[Hg]Cl>[CH3:41][O:42][C:43]1[CH:44]=[C:45]([NH:51][C:52]([NH:12][CH3:11])=[C:53]2[C:58](=[O:59])[O:57][C:56]([CH3:61])([CH3:60])[O:55][C:54]2=[O:62])[CH:46]=[CH:47][C:48]=1[O:49][CH3:50]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 578100945-[(3,4-Dimethoxy-phenylamino)-methylsulfanyl-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dioneHCID 57810280N-(3-fluoro-4-{[2-(methylamino)-6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 578101695-[(3,4-Dimethoxy-phenylamino)-methylamino-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dioneYield 99%

Reagents, catalysts & solvents 2

HCID 24085Mercuric ChlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Synthesis of ′N-(3-fluoro-4-{[2-(methylamino)-6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. A mixture of 5-[(3,4-dimethoxy-phenylamino)-methylsulfanyl-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dione (0.50 g, 1.4 mmol), methylamine (2 M in THF, 0.75 mL. 1.5 mmol), HgCl2 (0.38 g, 1.4 mmol) in THF (5 mL) was stirred at room temperature for 30 minutes. The mixture was extracted with DCM and water (3×) and dried with Na2SO4. Concentration in vacuo afforded 5-[(3,4-dimethoxy-phenylamino)-methylamino-methylene]-2,2-dimethyl-[1,3]dioxane-4,6-dione as a yellow solid (0.48 g, 99% yield) and this compound was used without further purification. LCMS: m/z 335 (M−H)−.

Workup

  1. extractionThe mixture was extracted with DCM and water (3×)
  2. dry with materialdried with Na2SO4
  3. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-d08a5503f6ad42f4a6397cfd285f03d0
Source dataset
uspto-grants-2011_11
Patent number
US08067436B2

Reaction notes

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