Sodium Hydroxide → (+/-)-2-[3-chloro-4-[(4-chlorophenyl)(2-pyridinyl-thio)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione

HRID 984044Notes

Reaction equation

HRID 984044 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:17]2[C:22](=[O:23])[NH:21][C:20](=[O:24])[CH:19]=[N:18]2)[CH:5]=[CH:6][C:7]=1[CH:8](Cl)[C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1.[SH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1.N12CCCN=C1CCCCC2.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:17]2[C:22](=[O:23])[NH:21][C:20](=[O:24])[CH:19]=[N:18]2)[CH:5]=[CH:6][C:7]=1[CH:8]([C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1)[S:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 225573573-chloro-4-[chloro(4-chlorophenyl)methyl]phenyl-1,2,4-triazine-3,5(2H,4H)-dioneHCID 178418616HCID 178418616, compound

Product 1

HCID 22557352(+/-)-2-[3-chloro-4-[(4-chlorophenyl)(2-pyridinyl-thio)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dioneYield 43.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-[3-chloro-4-[chloro(4-chlorophenyl)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione (0.015 mol) and 2-mercaptopyridine (0.04 mol) in THF (100 ml) was stirred overnight at RT. 1,8-diazabicyclo[5.4.0]undec-7-ene (0.03 mol) was added and the resulting reaction mixture was stirred for 3 hours. NaOH (1 N; 50 ml) was added. The mixture was stirred for 5 minutes, then extracted with EtOAc. The separated organic layer was washed with water, dried, filtered and the solvent evaporated. The aqueous layers were combined, then acidified (pH=6) with HCl (1 N). This mixture was extracted with CH2Cl2. The separated organic layer was dried, filtered, and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/THF/CH3OH 94/5/1). The pure fractions were collected and the solvent was evaporated. The residue was stirred overnight in diethyl ether. The solvent was evaporated. The residue was dried, yielding 2.98 g (43%) (±)-2-[3-chloro-4-[(4-chlorophenyl)(2-pyridinyl-thio)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione (compound 93).

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred for 3 hours
  3. stirringThe mixture was stirred for 5 minutes
  4. extractionextracted with EtOAc
  5. washThe separated organic layer was washed with water
  6. customdried
  7. filtrationfiltered
  8. customthe solvent evaporated
  9. extractionThis mixture was extracted with CH2Cl2
  10. customThe separated organic layer was dried
  11. filtrationfiltered
  12. customthe solvent was evaporated
  13. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/THF/CH3OH 94/5/1)
  14. customThe pure fractions were collected
  15. customthe solvent was evaporated
  16. stirringThe residue was stirred overnight in diethyl ether
  17. customThe solvent was evaporated
  18. customThe residue was dried

Sources & evidence

ORD record
ord-9eec077eb8ad4df9977c096e9181a153
Source dataset
uspto-grants-2005_03
Patent number
US06867207B2

Reaction notes

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