Methyl iodide → 2-Anilino-4-(1,2-diethylmethylimidazol-5-yl)pyrimidine

HRID 268588Notes

Reaction equation

HRID 268588 reaction equation
[NH:1]([C:8]1[N:13]=[C:12]([C:14]2[N:18]([CH2:19][CH3:20])[C:17]([CH3:21])=[N:16][C:15]=2[CH3:22])[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([Li])CCC.CCCCCC.IC>C1COCC1.O>[NH:1]([C:8]1[N:13]=[C:12]([C:14]2[N:18]([CH2:19][CH3:20])[C:17]([CH2:21][CH3:23])=[N:16][C:15]=2[CH3:22])[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8058Hexane2×HCID 692034322-Anilino-4-(1-ethyl-2,4dimethylimidazol-5-yl)pyrimidineHCID 178418339Butyllithium2×

Product 1

HCID 111625992-Anilino-4-(1,2-diethylmethylimidazol-5-yl)pyrimidineYield 13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

2-Anilino4-(l-ethyl-2,4dimethylimidazol-5-yl)pyrimidine (Method 11; 200 mg, 0.68 mmol) was dissolved in anhydrous THF (10 ml) under an inert atmosphere. The stirring solution was cooled using dry-ice/acetone bath to −70° C. A 1.6 M solution of n-butyl lithium in hexane (900 μl, 1.44 mmol) was added drop-wise keeping temperature <−60° C. until the dark red colour remained. At this point 1.6 M n-butyl lithium in hexane (450 μl, 0.72 mmol) was added and the solution stirred at −70° C. for 10 minutes. Iodomethane (99 μl, 1.50 mmol) was added, the temperature was maintained at −70° C. for an additional 10 minutes then allowed to rise to room temperature. The reaction was allowed to stir for 1 hr at room temperature when water (100 ml) was added. The aqueous layer extracted with EtOAc (2×20 ml). Organics were combined, dried solvent evaporated in vacuo. The residue was purified by flash silica chromatography DCM:MeOH (increasing in polarity from 100:0 to 96:4) to yield the title compound (28 mg, 13%). M/z 322.

Workup

  1. temperatureThe stirring solution was cooled
  2. customto −70° C
  3. customtemperature <−60° C.
  4. temperaturethe temperature was maintained at −70° C. for an additional 10 minutes
  5. customto rise to room temperature
  6. additionwas added
  7. extractionThe aqueous layer extracted with EtOAc (2×20 ml)
  8. customdried solvent evaporated in vacuo
  9. customThe residue was purified by flash silica chromatography DCM

Sources & evidence

ORD record
ord-58540e35fcbf4139a4e99b83c0abf106
Source dataset
uspto-grants-2008_11
Patent number
US07446105B2

Reaction notes

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