Pyrimidine-4-carbohydrazide → 7-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-3-(4-pyrimidinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HRID 1889081

Reaction equation

HRID 1889081 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH2:17][CH2:16][NH:15][C:14](=O)[CH2:13]1)=[O:11].F[B-](F)(F)F.C([O+](CC)CC)C.[N:31]1[CH:36]=[CH:35][C:34]([C:37]([NH:39][NH2:40])=O)=[N:33][CH:32]=1>ClCCl>[Cl:1][C:2]1[C:7]([F:8])=[C:6]([Cl:9])[CH:5]=[CH:4][C:3]=1[C:10]([N:12]1[CH2:17][CH2:16][N:15]2[C:37]([C:34]3[CH:35]=[CH:36][N:31]=[CH:32][N:33]=3)=[N:39][N:40]=[C:14]2[CH2:13]1)=[O:11]

Participants

5

Reactant 3

HCID 468664Pyrimidine-4-carbohydrazideHCID 2723982Triethyloxonium tetrafluoroborateHCID 665993614-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-2-piperazinone

Product 1

HCID 665991387-[(2,4-Dichloro-3-fluorophenyl)carbonyl]-3-(4-pyrimidinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[(2,4-dichloro-3-fluorophenyl)carbonyl]-2-piperazinone (I37) (0.364 g, 1.25 mmol) in Dichloromethane (DCM) (3 mL) was added triethyloxonium tetrafluoroborate (0.249 g, 1.313 mmol). The solution was then stirred, under argon, for 10 minutes before 4-pyrimidinecarbohydrazide (commercially available from e.g. Anichem, J&W PharmLab or Bepharm, 0.207 g, 1.500 mmol) was added. The solution was then stirred for a further hour before the solvent was concentrated and n-butanol (3.00 mL) was added. The solution was then stirred, under argon and reflux, for 3 hours before being cooled to room temperature. The solvent was then evaporated in vacuo and the remaining residue was purified by flash chromatography (Biotage SP4, 25M cartridge) with a gradient of 0-10% 2M NH3/MeOH in DCM. TLC confirmed product location and the solvent from the combined fractions were evaporated in vacuo. The remaining residue was then further purified by mass-direct automated HPLC, before the solvent was again evaporated in vacuo. The remaining solid was then triturated in ether before being dried in a vacuum oven to yield the product in 0.132 g.

Workup

  1. additionwas added
  2. concentrationwas concentrated
  3. additionn-butanol (3.00 mL) was added
  4. stirringThe solution was then stirred, under argon
  5. temperaturereflux, for 3 hours
  6. customThe solvent was then evaporated in vacuo
  7. customthe remaining residue was purified by flash chromatography (Biotage SP4, 25M cartridge) with a gradient of 0-10% 2M NH3/MeOH in DCM
  8. customthe solvent from the combined fractions were evaporated in vacuo
  9. customThe remaining residue was then further purified by mass-direct automated HPLC, before the solvent
  10. customwas again evaporated in vacuo
  11. customThe remaining solid was then triturated in ether
  12. custombefore being dried in a vacuum oven
  13. customto yield the product in 0.132 g

Sources & evidence

ORD record
ord-1246a69ef84944e584cc12c5a452d7f1
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Linked notes

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