Hexane → 3-[6-(4-Amino-2-fluorophenoxy)pyrimidin-4-yl]-1,1-dimethylurea

HRID 492727Notes

Reaction equation

HRID 492727 reaction equation
[F:1][C:2]1[CH:20]=[C:19]([N+:21]([O-])=O)[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:16])[N:13]([CH3:15])[CH3:14])[CH:6]=1.[Cl-].[NH4+].C(OCC)(=O)C.O1CCCC1.CCCCCC>C(O)C.O.C(OCC)C.[Fe]>[NH2:21][C:19]1[CH:18]=[CH:17][C:3]([O:4][C:5]2[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:16])[N:13]([CH3:15])[CH3:14])[CH:6]=2)=[C:2]([F:1])[CH:20]=1

Participants

9

Reactant 4

HCID 8058HexaneHCID 25517Ammonium ChlorideHCID 21939870Tetrahydrofuran ethyl acetateHCID 231530223-[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1,1-dimethylurea

Product 1

HCID 231531933-[6-(4-Amino-2-fluorophenoxy)pyrimidin-4-yl]-1,1-dimethylureaYield 83.6%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

3-[6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl]-1,1-dimethylurea (227 mg) was dissolved in ethanol (15 ml)-water (3 ml), and then electrolytic iron powder (230 mg) and ammonium chloride (460 mg) were added thereto, followed by heating under reflux for 30 min. The reaction mixture was cooled down to room temperature, and ethyl acetate-tetrahydrofuran (1:1) was then added thereto, followed by stirring. The reaction mixture was filtered through celite to remove an insoluble portion, which was washed with ethyl acetate and water. The organic layer of the filtrate was washed with 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=1:3). Fractions containing the target compound were concentrated under a reduced pressure to give a residue, which was suspended in diethyl ether (4 ml)-hexane (4 ml). The solid was filtered and dried under aeration to provide the titled compound (172 mg, 83.4%) as a pale yellow solid.

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 30 min
  3. filtrationThe reaction mixture was filtered through celite
  4. customto remove an insoluble portion, which
  5. washwas washed with ethyl acetate and water
  6. washThe organic layer of the filtrate was washed with 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; hexane:ethyl acetate=1:3)
  11. additionFractions containing the target compound
  12. concentrationwere concentrated under a reduced pressure
  13. customto give a residue, which
  14. filtrationThe solid was filtered
  15. customdried under aeration

Sources & evidence

ORD record
ord-ad12e3f281134431bad25b4c3e258c8a
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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