Diethyl Ether → N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamine

HRID 1872055Notes

Reaction equation

HRID 1872055 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:22][CH3:23])[C:12]1[N:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[C:14]([CH3:21])[N:13]=1.C[Li].[CH3:26]COCC.C(OCC)(=O)C>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:22][CH3:23])[C:12]1[N:17]=[C:16]([C:18](=[O:20])[CH3:26])[CH:15]=[C:14]([CH3:21])[N:13]=1

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 8857Ethyl AcetateHCID 18323680N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamineHCID 178418348HCID 178418348, compound2×

Product 1

HCID 18323676N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-acetyl-6-methylpyrimidinamineYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
78 °C

Procedure

A solution of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamine (3.7 g, 9.8 mmol) in anhydrous THF (25 mL) was cooled with stirring to 31 78° C. under a nitrogen atmosphere. A solution of methyl lithium in ether (1.4M, 7 mL, 9.8 mmol) was added dropwise and the reaction mixture was stirred at -78° C. for 1 h. The CeCl3 suspension was transferred via cannula into the reaction mixture and stirring at -78° C. was continued for 5 h. A solution of methyl lithium in ether (1.4M, 7 mL, 9.8 mmol) was added dropwise and the reaction mixture was then warmed gradually to room temperature over 16 h. After cooling the reaction mixture to -78° C., the reaction was quenched with a 1N HCl solution and warmed to room temperature. The resulting mixture was extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an orange yellow oil. Column chromatography (ethyl acetate:hexanes::1:4) afforded the title product as an oil (2.5 g, 68% yield, Rf 0.5): NMR (CDCl3, 300 MHz): 7.55 (d, 1H, J=1), 7.25-7.15 (m, 2H), 6.95 (s, 1H), 4.30-4.10 (m, 1H), 3.90-3.70 (m, 1H), 3.00-2.85 (m, 1H), 2.80-2.05 (m, 6H), 1.35-1.20 (m, 9H); CI-HRMS: Calcd (C18H22BrN3O): 376.1024 (M+H), Found: 376.1042.

Workup

  1. stirringthe reaction mixture was stirred at -78° C. for 1 h
  2. stirringstirring at -78° C.
  3. temperaturethe reaction mixture was then warmed gradually to room temperature over 16 h
  4. temperatureAfter cooling the reaction mixture to -78° C.
  5. customthe reaction was quenched with a 1N HCl solution
  6. temperaturewarmed to room temperature
  7. extractionThe resulting mixture was extracted three times with ethyl acetate
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give an orange yellow oil

Sources & evidence

ORD record
ord-f2f1b322156849cf94c7cfeeb4e2fde0
Source dataset
uspto-grants-2000_08
Patent number
US06107301

Reaction notes

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