Acetic Acid → N-(4-bromophenyl)-N'-[4-ethoxy-6-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl]-N-methylurea

HRID 907418Notes

Reaction equation

HRID 907418 reaction equation
[H-].[Na+].CCO.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([CH3:35])[C:14]([NH:16][C:17]2[N:22]=[C:21]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[CH:20]=[C:19]([O:29][CH2:30][C:31](F)(F)F)[N:18]=2)=[O:15])=[CH:9][CH:8]=1.C(O)(=O)C>CN(C=O)C>[Br:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([CH3:35])[C:14]([NH:16][C:17]2[N:18]=[C:19]([O:29][CH2:30][CH3:31])[CH:20]=[C:21]([O:23][CH2:24][C:25]([F:27])([F:26])[F:28])[N:22]=2)=[O:15])=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 702EthanolHCID 24758Sodium hydrideHCID 57651736HCID 57651736, compound

Product 1

HCID 57651702N-(4-bromophenyl)-N'-[4-ethoxy-6-(2,2,2-trifluoroethoxy)-pyrimidin-2-yl]-N-methylureaYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a suspension of NaH (320 mg, 8.0 mmol, 60% dispersion in mineral oil) in anhydrous DMF (5 mL) under an N2 atmosphere was added anhydrous EtOH (583 μL, 10 mmol). To this solution was added a solution of N-(4-bromophenyl)-N′-[4,6-bis(2,2,2-trifluoroethoxy)pyrimidin-2-yl]-N-methylurea (1.0 g, 2.0 mmol), prepared in a manner similar to 7, in anhydrous DMF (3 mL). The resulting solution was heated (ca. 60° C.) for 2 h, the heat was removed and the solution cooled to room temperature. The solution was diluted with EtOAc (100 mL) and extracted with 2 N HCl (2×50 mL). The organics were dried over MgSO4, filtered and concentrated to afford a brown oil. The brown oil was eluted through a plug of silica using a mixture of hexane and EtOAc and the resulting organic solution concentrated to afford a yellow oil. The yellow oil was further purified by reverse phase chromatography (HPLC grade acetonitrile and water, both with 0.1% acetic acid) to afford 103 as a yellow tacky oil (186 mg, 41% yield): 1H NMR (CDCl3) δ 7.64 (d, 2H, J=8.8 Hz), 7.24 (d, 2H, J=8.8 Hz), 6.84 (s, 1H), 4.81-4.72 (q, 2H, J=8.5 Hz), 4.33-4.26 (q, 2H J=7.1 Hz), 1.39-1.37 (t, 3H, J=7.1 Hz); ESI/MS 449, 451 (M+H), 447, 449 (M−H).

Workup

  1. customthe heat was removed
  2. temperaturethe solution cooled to room temperature
  3. additionThe solution was diluted with EtOAc (100 mL)
  4. extractionextracted with 2 N HCl (2×50 mL)
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a brown oil
  9. washThe brown oil was eluted through a plug of silica using
  10. additiona mixture of hexane and EtOAc
  11. concentrationthe resulting organic solution concentrated
  12. customto afford a yellow oil
  13. customThe yellow oil was further purified by reverse phase chromatography (HPLC grade acetonitrile and water

Sources & evidence

ORD record
ord-e7feed81898a41e5bf688189e90e79cd
Source dataset
uspto-grants-2011_09
Patent number
US08013154B2

Reaction notes

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