Methylamine → 1-(2-Fluoro-4-iodophenyl)-3-methylurea

HRID 75665Notes

Reaction equation

HRID 75665 reaction equation
C1N=[CH:4][N:3]([C:6]([N:8]2C=N[CH:10]=[CH:9]2)=[O:7])C=1.C(N(CC)CC)C.[F:20][C:21]1[CH:27]=[C:26]([I:28])[CH:25]=CC=1N.CN>CN(C)C=O.CO.O.C1(C)C=CC=CC=1>[F:20][C:21]1[CH:27]=[C:26]([I:28])[CH:25]=[CH:10][C:9]=1[NH:8][C:6]([NH:3][CH3:4])=[O:7]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 1856942-Fluoro-4-iodoaniline

Product 1

HCID 597173511-(2-Fluoro-4-iodophenyl)-3-methylureaYield 94.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 22272177Toluene waterSolvent

Procedure

Under a nitrogen atmosphere, to N,N-carbonyldiimidazole (61.4 g) were added N,N-dimethylformamide (300 ml) and triethylamine (52.8 ml) and a solution of 2-fluoro-4-iodoaniline 47 (74.8 g) in N,N-dimethylformamide (75 ml) was added dropwise with stirring under ice-cooling. After the completion of the dropwise addition, the mixture was stirred at room temperature for 5 hrs. The reaction mixture was ice-cooled, and a solution (60 ml) of 40% methylamine in methanol was added dropwise. The mixture was stirred at room temperature for 1 hr, and the reaction mixture was added dropwise to water-toluene [2:1 (volume ratio), 1125 ml] under stirring. The precipitated crystals were collected by filtration and dried to give 1-(2-fluoro-4-iodophenyl)-3-methylurea 63 (87.9 g, yield 94.8%) as colorless crystals.

Workup

  1. temperaturecooling
  2. additionAfter the completion of the dropwise addition
  3. stirringthe mixture was stirred at room temperature for 5 hrs
  4. temperaturecooled
  5. stirringThe mixture was stirred at room temperature for 1 hr
  6. stirringunder stirring
  7. filtrationThe precipitated crystals were collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-9f5faabee287429ebdb6145a23e54304
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

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