HCID 3811668, compound → HCID 178441736, compound

HRID 2082036Notes

Reaction equation

HRID 2082036 reaction equation
N1(C[N:7]2[CH:11]=[CH:10][CH:9]=[N:8]2)CCCC1.C([Li])CCC.[CH3:17][C:18]([C:21]1[C:26]([OH:27])=[C:25]([C:28]([CH3:31])([CH3:30])[CH3:29])[N:24]=[C:23]([C:32](N(OC)C)=[O:33])[N:22]=1)([CH3:20])[CH3:19]>O1CCCC1.C1CCCCC1>[CH3:20][C:18]([C:21]1[C:26]([OH:27])=[C:25]([C:28]([CH3:31])([CH3:30])[CH3:29])[N:24]=[C:23]([C:32]([C:11]2[CH:10]=[CH:9][NH:8][N:7]=2)=[O:33])[N:22]=1)([CH3:17])[CH3:19]

Participants

6

Reactant 3

HCID 3811668HCID 3811668, compoundHCID 100401704,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamideHCID 178418339Butyllithium

Product 1

HCID 178441736HCID 178441736, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-(1-pyrrolidinomethyl)pyrazole (0.64 g, 4.2 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 2.1M solution of n-butyllithium (2.0 mL, 4.20 mmol) in cyclohexane. The resulting mixture is stirred 1 hour at -78° C. and warmed to ~0° C. After stirring 0.5 hours at 0° C., this mixture is cannula transferred to a solution of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide in tetrahydrofuran (10 mL) at ~0° C. This reaction mixture is warmed to room temperature and stirred 16 hours. After quenching with aqueous saturated ammonium chloride solution, the mixture is extracted with ethyl acetate and the combined extracts washed with brine. The organic phase is dried over magnesium sulfate and concentrated under vacuum. The organic residue is purified by flash chromatography (SiO2, 10% methanol/hexane) followed by recrystallization from isopropanol and water to give 0.22 g (43%) of title compound as a mixture of tautomers, mp 156°-161° C.

Workup

  1. temperaturewarmed to ~0° C
  2. stirringAfter stirring 0.5 hours at 0° C.
  3. temperatureThis reaction mixture is warmed to room temperature
  4. stirringstirred 16 hours
  5. customAfter quenching with aqueous saturated ammonium chloride solution
  6. extractionthe mixture is extracted with ethyl acetate
  7. washthe combined extracts washed with brine
  8. dry with materialThe organic phase is dried over magnesium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe organic residue is purified by flash chromatography (SiO2, 10% methanol/hexane)
  11. customfollowed by recrystallization from isopropanol and water

Sources & evidence

ORD record
ord-a6b8da13f5374feb8753e3aeb252c8a3
Source dataset
uspto-grants-1993_02
Patent number
US05187175

Reaction notes

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