2-Hydrazinylpyrimidine → 2-[5-(4-Fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-1-yl]pyrimidine

HRID 1032450Notes

Reaction equation

HRID 1032450 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10](=O)[CH:11]([CH3:13])[CH3:12])=[CH:4][CH:3]=1.[NH:16]([C:18]1[N:23]=[CH:22][CH:21]=[CH:20][N:19]=1)[NH2:17].C([O-])(O)=O.[Na+]>C(O)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([C:18]3[N:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[N:17]=[C:10]([CH:11]([CH3:13])[CH3:12])[CH:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 3465582-HydrazinylpyrimidineHCID 516892Sodium BicarbonateHCID 141543761-(4-Fluorophenyl)-4-methylpentane-1,3-dione

Product 1

HCID 148513212-[5-(4-Fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-1-yl]pyrimidine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-(4-fluorophenyl)-4-methyl-1,3-pentanedione (preparation disclosed in Example 1, Step A) (155 g, 0.74 mol) in 1 l glacial acetic acid was added, under a N2 atmosphere at room temperature, 90 g (0.82 mol) of 2-hydrazinopyrimidine (prepared according to J. Chesterfield et al., J. Chem. Soc., 3478, 1955). This was heated to 60° C. for one hour, cooled to room temperature and poured into 4 l saturated NaHCO3 aqueous solution. The resulting mixture was extracted with EtOAc and the organic layer was separated and washed with water and brine. This solution was dried over MgSO4, filtered and concentrated in vacuo. The crude reaction mixture was flash chromatographed on a silica gel column, eluting with 10% EtOAc-toluene yielding 16.4 g of 2-[5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-1-yl]pyrimidine and 94 g of 5(3)-4-fluorophenyl)-3(5)-(1-methylethyl)-1H-pyrazole, mp 102°-103° C.

Workup

  1. temperaturecooled to room temperature
  2. extractionThe resulting mixture was extracted with EtOAc
  3. customthe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialThis solution was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude reaction mixture
  9. customchromatographed on a silica gel column
  10. washeluting with 10% EtOAc-toluene yielding 16.4 g of 2-[5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-1-yl]pyrimidine and 94 g of 5(3)-4-fluorophenyl)-3(5)-(1-methylethyl)-1H-pyrazole, mp 102°-103° C.

Sources & evidence

ORD record
ord-ebfd8adb12cd46a398360b8333eab413
Source dataset
uspto-grants-1990_09
Patent number
US04957971

Reaction notes

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