Hydrochloric Acid → HCID 66599056, compound

HRID 1889074Notes

Reaction equation

HRID 1889074 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([N:11]1[CH2:16][CH2:15][NH:14][C:13](=O)[CH2:12]1)=[O:10].F[B-](F)(F)F.C([O+](CC)CC)C.[CH3:30][C:31]1[C:32]([C:37]([NH:39][NH2:40])=O)=[N:33][CH:34]=[CH:35][CH:36]=1.Cl>ClCCl.CO.C(OCC)C>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([N:11]1[CH2:16][CH2:15][N:14]2[C:37]([C:32]3[C:31]([CH3:30])=[CH:36][CH:35]=[CH:34][N:33]=3)=[N:39][N:40]=[C:13]2[CH2:12]1)=[O:10]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 2723982Triethyloxonium tetrafluoroborateHCID 221382343-Methylpyridine-2-carbohydrazide2×HCID 25537116HCID 25537116, compound2×

Product 1

HCID 66599056HCID 66599056, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-[(2-chloro-4-fluorophenyl)carbonyl]-2-piperazinone (0.257 g, 1 mmol, e.g. prepared as described in Intermediate 2) in dry Dichloromethane (DCM) (2 ml) was stirred at room temperature under argon. Triethyloxonium tetrafluoroborate (0.190 g, 1.000 mmol) was added and the reaction solution was stirred for 3 hours. 3-Methyl-2-pyridinecarbohydrazide (0.166 g, 1.100 mmol, e.g. prepared as described in Intermediate 22) was added to the solution and stirred for 1 h. The solvent was then evaporated in vacuo and n-butanol (2.000 ml) was added to the residue. The solution was heated at reflux for 18 hours and then allowed to cool to room temperature. The solvent was then evaporated in vacuo and the residue was partitioned between Dichloromethane and brine. The organic layer was dried over sodium sulphate, filtered and the solvent was evaporated in vacuo to give a yellow solid. The solid was then purified by flash chromatography (Biotage SP4, 25+M cartridge) using a gradient of 0 to 10% MeOH/NH3 in Dichloromethane as the eluent. The solvent was then evaporated in vacuo and the remaining residue was purified by mass-directed automated (preparative) HPLC (MDAP) to yield the crude product. The product was then dissolved in methanol (2 mL) and to this was added HCl in diethyl ether (1 mL), the solvent was then evaporated in vacuo and dried in a vacuum-oven yielding 7-[(2-chloro-4-fluorophenyl)carbonyl]-3-(3-methyl-2-pyridinyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (0.108 g).

Workup

  1. stirringstirred for 1 h
  2. customThe solvent was then evaporated in vacuo and n-butanol (2.000 ml)
  3. additionwas added to the residue
  4. temperatureThe solution was heated
  5. temperatureat reflux for 18 hours
  6. customThe solvent was then evaporated in vacuo
  7. customthe residue was partitioned between Dichloromethane and brine
  8. dry with materialThe organic layer was dried over sodium sulphate
  9. filtrationfiltered
  10. customthe solvent was evaporated in vacuo
  11. customto give a yellow solid
  12. customThe solid was then purified by flash chromatography (Biotage SP4, 25+M cartridge)
  13. customThe solvent was then evaporated in vacuo
  14. customthe remaining residue was purified
  15. customto yield the crude product
  16. customthe solvent was then evaporated in vacuo
  17. customdried in a vacuum-oven

Sources & evidence

ORD record
ord-fe22bddf37444fbf83e13b8a0430f9da
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Reaction notes

Loading…