Acetic Acid → 7-Chloro-2-methyl-6-phenyl-imidazo[1,2-a]pyrimidine

HRID 1851186Notes

Reaction equation

HRID 1851186 reaction equation
Cl[C:2]1[N:7]2[CH:8]=[C:9]([CH3:11])[N:10]=[C:6]2[N:5]=[C:4]([Cl:12])[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(O)(=O)C>CO.C1COCC1>[Cl:12][C:4]1[C:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:2][N:7]2[CH:8]=[C:9]([CH3:11])[N:10]=[C:6]2[N:5]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 866903015,7-Dichloro-2-methyl-6-phenyl-imidazo[1,2-a]pyrimidine

Product 1

HCID 866903007-Chloro-2-methyl-6-phenyl-imidazo[1,2-a]pyrimidineYield 3.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

8.3 g (30 mmol) 5,7-Dichloro-2-methyl-6-phenyl-imidazo[1,2-a]pyrimidine are dissolved in 14.5 mL methanol and 85 mL THF. After addition of 3.4 mL acetic acid 5.8 g (45 mmol) zinc/copper pair are added in portions and the mixture is stirred at rt for four and a half hours. The reaction mixture is filtered via a glass microfibre filter and washed with plenty of methanol. The solvent has been removed and the residue redissolved in ethyl acetate. After washing twice with brine and drying over Na2SO4, the solvent is evaporated and the residue purified by chromatography on silica gel (dichloromethane/methanol) yielding only 260 mg of the desired compound. 2N NaOH is added to the zinc/copper slurry of the reaction until a pH of 8. Afterwards the slurry is treated four times with 300 mL ethyl acetate/methanol (1%) each. The solvent mixture is decanted each time and the extracts are combined. After evaporation of the solvents 3.1 g of the desired product are obtained. Repetition of this process yields additional 2.32 g product. Altogether 74.4% of the desired material have been obtained.

Workup

  1. additionare added in portions
  2. filtrationThe reaction mixture is filtered via a glass microfibre
  3. filtrationfilter
  4. washwashed with plenty of methanol
  5. customThe solvent has been removed
  6. dissolutionthe residue redissolved in ethyl acetate
  7. washAfter washing twice with brine
  8. dry with materialdrying over Na2SO4
  9. customthe solvent is evaporated
  10. customthe residue purified by chromatography on silica gel (dichloromethane/methanol)

Sources & evidence

ORD record
ord-f75270499a4b468e869067ecb1b3f87e
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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