1-(1H-Imidazol-1-yl)-N,N-dimethylmethanamine → [4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl](1H-imidazol-2-yl)methanone

HRID 2082035Notes

Reaction equation

HRID 2082035 reaction equation
CN(C[N:5]1[CH:9]=[CH:8][N:7]=[CH:6]1)C.C([Li])CCC.[CH3:15][C:16]([C:19]1[C:24]([OH:25])=[C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])[N:22]=[C:21]([C:30](N(OC)C)=[O:31])[N:20]=1)([CH3:18])[CH3:17]>O1CCCC1>[CH3:18][C:16]([C:19]1[C:24]([OH:25])=[C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])[N:22]=[C:21]([C:30]([C:6]2[NH:5][CH:9]=[CH:8][N:7]=2)=[O:31])[N:20]=1)([CH3:15])[CH3:17]

Participants

5

Reactant 3

HCID 38320731-(1H-Imidazol-1-yl)-N,N-dimethylmethanamineHCID 100401704,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamideHCID 178418339Butyllithium

Product 1

HCID 19779331[4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl](1H-imidazol-2-yl)methanoneYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-[(dimethylamino)methyl]-imidazole (0.70 g, 5.6 mmol) (See Katritzky, A. R.; Rewcastle, G. W.; Fan, W-Q; J. Org. Chem. 1988, 53, 5688) in tetrahydrofuran (10 mL) at -78° C. under nitrogen atmosphere is added a 1.58M solution of n-butyllithium (3.60 mL, 5.69 mmol) in hexanes dropwise. The resulting mixture is stirred 1 hour at -78° C., warmed to ~0° C., and stirred 0.5 hours. After cooling to -78° C., 4,6-bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide (0.50 g, 1.7 mmol) in tetrahydrofuran (5 mL) is added. This mixture is warmed to room temperature, stirred for 16 hours, and quenched by addition of aqueous 2N hydrochloric acid solution. After extraction with ethyl acetate, the combined extracts are washed with water and brine solution. Concentration of the organic phase under vacuum followed by recrystallization of the organic residue from methanol and water gives 0.43 g (84%) of the title compound, mp 217°-220° C.

Workup

  1. temperaturewarmed to ~0° C.
  2. stirringstirred 0.5 hours
  3. temperatureAfter cooling to -78° C.
  4. temperatureThis mixture is warmed to room temperature
  5. stirringstirred for 16 hours
  6. customquenched by addition of aqueous 2N hydrochloric acid solution
  7. extractionAfter extraction with ethyl acetate
  8. washthe combined extracts are washed with water and brine solution
  9. customConcentration of the organic phase under vacuum followed by recrystallization of the organic residue from methanol and water

Sources & evidence

ORD record
ord-8a21f3db03b84472bd8ad950252abf16
Source dataset
uspto-grants-1993_02
Patent number
US05187175

Reaction notes

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