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

HRID 75655Notes

Reaction equation

HRID 75655 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 95.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 22272177Toluene waterSolvent

Procedure

Under a nitrogen atmosphere, to N,N-carbonyldiimidazole (82.1 g) were added N,N-dimethylformamide (400 ml) and triethylamine (70.5 ml), and a solution of 2-fluoro-4-iodoaniline 47 (100 g) in N,N-dimethylformamide (100 ml) was added dropwise 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 cyclopropylamine (44.0 ml) 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), 1500 ml] with stirring. The precipitated crystals were collected by filtration and dried to give 1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-urea 48 (129 g, yield 95.5%) as colorless crystals.

Workup

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

Sources & evidence

ORD record
ord-b9f36db25f2444b0bb2ef0e5d1361928
Source dataset
uspto-grants-2014_09
Patent number
US08835443B2

Reaction notes

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