Triethylamine → 3-[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1-(3-diethylaminopropyl)-1-methylurea

HRID 492762Notes

Reaction equation

HRID 492762 reaction equation
[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1.[CH2:19]([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH3:20].ClC([O:29][C:30]1C=CC=CC=1)=O.[CH2:36]([N:38](CC)[CH2:39]CCNC)C>O1CCCC1.CN(C)C=O>[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:30](=[O:29])[N:38]([CH2:39][CH2:20][CH2:19][N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH3:36])[CH:6]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 79577N,N-Diethyl-N'-methyl-1,3-propanediamineHCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

Product 1

HCID 231532583-[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1-(3-diethylaminopropyl)-1-methylureaYield 66.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-ylamine (50 mg) was dissolved in tetrahydrofuran (2 ml) under a nitrogen atmosphere, and then triethylamine (0.0697 ml) and phenyl chloroformate (0.0627 ml) were added thereto while cooling in an ice bath, followed by stirring at room temperature for 30 min. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (2 ml) and N,N-diethyl-N′-methylpropane-1,3-diamine (115 mg) were added, followed by stirring at room temperature for 2 hrs. 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, 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 purified by silica gel column chromatography (eluent; hexane:ethyl acetate=2:1 to 1:1, then ethyl acetate:ethanol=19:1). Fractions containing the target compound were concentrated under a reduced pressure to give a residue, which was then dried in vacuum to provide the titled compound (55.7 mg, 66.2%) as a yellow solid.

Workup

  1. temperaturewhile cooling in an ice bath
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring at room temperature for 2 hrs
  5. customThe reaction mixture was partitioned between ethyl acetate
  6. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride, water and brine in this order
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under a reduced pressure
  9. customto give a residue, which
  10. customwas then purified by silica gel column chromatography (eluent
  11. additionFractions containing the target compound
  12. concentrationwere concentrated under a reduced pressure
  13. customto give a residue, which
  14. customwas then dried in vacuum

Sources & evidence

ORD record
ord-7aef298a46a24e3db31e7f7578cb8d90
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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