3H-1,2,4-Triazole-3-thione, 2,4-dihydro-4-methyl- → HCID 178481706, compound

HRID 2217749Notes

Reaction equation

HRID 2217749 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[N:10][NH:9][C:8]1=[S:12].[Cl:13][C:14]1[CH:42]=[CH:41][C:17]([C:18]([C:20]2[CH:32]=[C:30]3[C:31]4[N:26]([CH2:27][CH2:28][CH2:29]3)[C:25](=[O:33])[CH:24]=[C:23]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=3)[C:22]=4[CH:21]=2)=[O:19])=[CH:16][CH:15]=1>C1COCC1>[OH2:19].[Cl:40][C:36]1[CH:35]=[C:34]([C:23]2[C:22]3[CH:21]=[C:20]([C:18]([C:17]4[CH:16]=[CH:15][C:14]([Cl:13])=[CH:42][CH:41]=4)([OH:19])[C:11]4[N:7]([CH3:6])[C:8]([SH:12])=[N:9][N:10]=4)[CH:32]=[C:30]4[CH2:29][CH2:28][CH2:27][N:26]([C:25](=[O:33])[CH:24]=2)[C:31]=34)[CH:39]=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 12561623H-1,2,4-Triazole-3-thione, 2,4-dihydro-4-methyl-HCID 690401099-(4-chlorobenzoyl)-7-(3-chlorophenyl)-2,3-dihydro-1H,5H-benzo[ij]quinolizin-5-oneHCID 178418339Butyllithium

Product 1

HCID 178481706HCID 178481706, compoundYield 39.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

n-BuLi (0.0166 mol) was added slowly at −78° C. to a solution of 2,4-dihydro-4-methyl-3H-1,2,4-triazole-3-thione (0.0082 mol) in THF (50 ml) under N2 flow. The mixture was stirred at 0° C. for 1 hour, then cooled to −78° C. 9-(4-chlorobenzoyl)-7-(3-chlorophenyl)-2,3-dihydro-1H,5H-benzo[ij]quinolizin-5-one (described in International Application WO98/40383) (0.0046 mol) was added portionwise. The mixture was stirred at room temperature for 4 hours, poured out on ice and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (2.32 g) was purified by column chromatography over silica gel (15-40 μm) (eluent: CH2Cl2/CH3OH/NH4OH 98/2/0.1 to 96/4/0.1). The pure fractions were collected and the solvent was evaporated. The residue (1 g, 40%). was crystallized from acetonitril. The precipitate was filtered off and dried, yielding 0.52 g (21%) of 7-(3-chlorophenyl)-9-[(4-chlorophenyl)hydroxy(5-mercapto-4-methyl-4H-1,2,4-triazol-3-yl)methyl]-2,3-dihydro-1H,5H-benzo[ij]quinolizin-5-one hydrate (1:1), melting point 160° C. (intermediate 7).

Workup

  1. temperaturecooled to −78° C
  2. stirringThe mixture was stirred at room temperature for 4 hours
  3. additionpoured out on ice
  4. extractionextracted with EtOAc
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue (2.32 g) was purified by column chromatography over silica gel (15-40 μm) (eluent: CH2Cl2/CH3OH/NH4OH 98/2/0.1 to 96/4/0.1)
  10. customThe pure fractions were collected
  11. customthe solvent was evaporated
  12. customwas crystallized from acetonitril
  13. filtrationThe precipitate was filtered off
  14. customdried

Sources & evidence

ORD record
ord-8e27e67ff87c4732847983b7c18c6096
Source dataset
uspto-grants-2008_08
Patent number
US07408063B2

Reaction notes

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