Triethylamine → N-Cyclopropyl-N'-(2-fluoro-4-iodophenyl)urea

HRID 75648Notes

Reaction equation

HRID 75648 reaction equation
[CH:1]1N=C[N:3]([C:6]([N:8]2C=N[CH:10]=[CH:9]2)=[O:7])[CH:2]=1.[CH2:13](N(CC)CC)C.[F:20][C:21]1[CH:27]=[C:26]([I:28])[CH:25]=CC=1N.C1(N)CC1>CN(C)C=O.O.C1(C)C=CC=CC=1>[CH:9]1([NH:8][C:6]([NH:3][C:2]2[CH:1]=[CH:25][C:26]([I:28])=[CH:27][C:21]=2[F:20])=[O:7])[CH2:10][CH2:13]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 69828CyclopropylamineHCID 1856942-Fluoro-4-iodoaniline

Product 1

HCID 59717054N-Cyclopropyl-N'-(2-fluoro-4-iodophenyl)ureaYield 93.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 22272177Toluene waterSolvent

Procedure

Under a nitrogen atmosphere, to N,N-carbonyldiimidazole (39.9 g) were added N,N-dimethylformamide (200 ml) and triethylamine (34.3 ml) and a solution of 2-fluoro-4-iodoaniline 47 (48.5 g) in N,N-dimethylformamide (50 ml) was added dropwise with stirring under ice-cooling. After the completion of the dropwise addition, the mixture was stirred at room temperature for 18 hrs. The reaction mixture was ice-cooled, and cyclopropylamine (21.3 ml) was added dropwise. The reaction mixture was stirred at room temperature for 1 hr and added dropwise to water-toluene [2:1 (volume ratio), 750 ml] with stirring. The precipitated crystals were collected by filtration and dried to give 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)urea 48 (61.3 g, yield 93.4%) as colorless crystals.

Workup

  1. temperaturecooling
  2. additionAfter the completion of the dropwise addition
  3. stirringthe mixture was stirred at room temperature for 18 hrs
  4. temperaturecooled
  5. stirringThe reaction mixture was stirred at room temperature for 1 hr
  6. stirringwith stirring
  7. filtrationThe precipitated crystals were collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-b83af1a5c8c745d3acecb5894ea8008b
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

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