Water → 5-Chloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine

HRID 1851168Notes

Reaction equation

HRID 1851168 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[C:6](Cl)[N:5]2[N:16]=[C:17]([CH:19]3[CH2:21][CH2:20]3)[N:18]=[C:4]2[N:3]=1.O.C1COCC1.[NH4+].[Cl-]>C(O)C.[Zn]>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][N:5]2[N:16]=[C:17]([CH:19]3[CH2:21][CH2:20]3)[N:18]=[C:4]2[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 867030295,7-Dichloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine

Product 1

HCID 867030285-Chloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidineYield 10.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 702EthanolSolvent

Procedure

7.78 g (24.1 mmol) 5,7-Dichloro-2-cyclopropyl-6-(4-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine are given in 612 mL ethanol, 435 mL water and 234 mL THF. After addition of 6.1 g (114 mmol) NH4Cl, 10.1 g (154 mmol) zinc powder are added and the mixture is stirred at room temperature for 3 h. Stirring is continued over night. The reaction mixture is filtered via a glass microfibre filter and the filter is washed with plenty of methanol. The zinc slurry is stirred twice with ethylacetate/methanol (250 mL each) and the combined organic filtrates are evaporated. The residue is extracted with ethyl acetate (1 L). The organic phase is washed twice with brine and dried over Na2SO4. After evaporation of the solvent, the residue is purified by chromatography on silicagel (eluents dichloromethane/methanol) yielding 0.76 g (10.4%) of the desired product. Additionally 3.57 g are obtained which are a mixture of the desired product and the bis deschloro derivate (ratio 6:4).

Workup

  1. additionare added
  2. stirringStirring
  3. waitis continued over night
  4. filtrationThe reaction mixture is filtered via a glass microfibre
  5. filtrationfilter
  6. washthe filter is washed with plenty of methanol
  7. stirringThe zinc slurry is stirred twice with ethylacetate/methanol (250 mL each)
  8. customthe combined organic filtrates are evaporated
  9. extractionThe residue is extracted with ethyl acetate (1 L)
  10. washThe organic phase is washed twice with brine
  11. dry with materialdried over Na2SO4
  12. customAfter evaporation of the solvent
  13. customthe residue is purified by chromatography on silicagel (eluents dichloromethane/methanol)

Sources & evidence

ORD record
ord-40456d9a54df4764ab5d7ab8b8c3111d
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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