Dimethylamine → 3-[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1,1-dimethylurea

HRID 492726Notes

Reaction equation

HRID 492726 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=2[F:18])[N:5]=[CH:4][N:3]=1.[CH2:19]([N:21]([CH2:24]C)[CH2:22]C)C.ClC(OC1C=CC=CC=1)=[O:28].CNC>O1CCCC1.C(OCC)C.CO>[F:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:1][C:19](=[O:28])[N:21]([CH3:24])[CH3:22])[CH:7]=1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 8471Triethylamine3×HCID 15891Phenyl chloroformate3×HCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

Product 1

HCID 231530223-[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1,1-dimethylureaYield 59%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine (500 mg) was dissolved in tetrahydrofuran (10 ml) under a nitrogen atmosphere, and then triethylamine (0.418 ml) and phenyl chloroformate (0.376 ml) were added dropwise thereto while cooling in an ice bath, followed by stirring at room temperature for 1 hr and 10 min. Triethylamine (0.139 ml) and phenyl chloroformate (0.125 ml) were added further thereto while cooling in an ice bath, followed by stirring at room temperature for 30 min. Triethylamine (0.139 ml) and phenyl chloroformate (0.125 ml) were added further thereto, followed by stirring at room temperature for 30 min. To the reaction mixture was added 2 M dimethylamine (a methanol solution) (5.0 ml), followed by stirring at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer was washed with a saturated aqueous solution of ammonium chloride, a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then suspended in diethyl ether. The solid was filtered, and dried under aeration to provide the titled compound (378.9 mg, 59.0%) as pale yellow powder.

Workup

  1. temperaturewhile cooling in an ice bath
  2. temperaturewhile cooling in an ice bath
  3. stirringby stirring at room temperature for 30 min
  4. stirringby stirring at room temperature for 30 min
  5. stirringby stirring at room temperature overnight
  6. customThe reaction mixture was partitioned between ethyl acetate
  7. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride
  8. dry with materiala saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, and dried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under a reduced pressure
  10. customto give a residue, which
  11. filtrationThe solid was filtered
  12. customdried under aeration

Sources & evidence

ORD record
ord-6c19cc9bca0340da919fe87cca37a4e3
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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