Hydrochloric Acid → (+/-)-2-[3-chloro-4-[(4-chlorophenyl)hydroxy(4-phenyl-2-thiazolyl)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione

HRID 984041Notes

Reaction equation

HRID 984041 reaction equation
C([Li])CCC.[C:6]1([C:12]2[N:13]=[CH:14][S:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[Cl:17][C:18]1[CH:19]=[C:20]([N:33]2[C:38](=[O:39])[NH:37][C:36](=[O:40])[CH:35]=[N:34]2)[CH:21]=[CH:22][C:23]=1[C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1.Cl>C(OCC)C.C1COCC1>[Cl:17][C:18]1[CH:19]=[C:20]([N:33]2[C:38](=[O:39])[NH:37][C:36](=[O:40])[CH:35]=[N:34]2)[CH:21]=[CH:22][C:23]=1[C:24]([C:25]1[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=1)([OH:32])[C:14]1[S:15][CH:16]=[C:12]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:13]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 74581Thiazole, 4-phenyl-HCID 161969CP 25415HCID 178418339Butyllithium

Product 1

HCID 22557363(+/-)-2-[3-chloro-4-[(4-chlorophenyl)hydroxy(4-phenyl-2-thiazolyl)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dioneYield 11%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

n-Butyl lithium (0.045 mol) was added at −70° C. under N2 flow to a solution of 4-phenyl-thiazole (0.045 mol) in diethyl ether (50 ml). The mixture was stirred at −70° C. for 90 minutes. A solution of 2-[3-chloro-4-(4-chlorobenzoyl)phenyl]-1,2,4-triazine-3,5-(2H,4H)-dione (0.015 mol) in THF (10 ml) was added at −70° C. The mixture was stirred at −70° C. for 1 hour, then poured out into ice water, neutralized with HCl 3N and extracted with EtOAc. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography oversilica gel (eluent: CH2Cl2/CH3OH 98/2). The desired fraction was repurified by HPLC (eluent: CH3OH/(NH4OAc 1% in H2O) 80/20). The pure fractions were collected and the solvent was evaporated, yielding 0.83 g (11%) of (±)-2-[3-chloro-4-[(4-chlorophenyl)hydroxy(4-phenyl-2-thiazolyl)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione (interm. 71).

Workup

  1. stirringThe mixture was stirred at −70° C. for 1 hour
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified by column chromatography oversilica gel (eluent: CH2Cl2/CH3OH 98/2)
  8. customThe desired fraction was repurified by HPLC (eluent: CH3OH/(NH4OAc 1% in H2O) 80/20)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated

Sources & evidence

ORD record
ord-f46a8188ef6d49a0b31f05004db37238
Source dataset
uspto-grants-2005_03
Patent number
US06867207B2

Reaction notes

Loading…