Hexane → HCID 178481707, compound

HRID 2217750Notes

Reaction equation

HRID 2217750 reaction equation
[Li]CCCC.CCCCCC.[CH3:12][N:13]1[CH:17]=[N:16][NH:15][C:14]1=[S:18].[Cl:19][C:20]1[CH:47]=[CH:46][C:23]([C:24]([C:26]2[CH:27]=[C:28]3[C:33]4=[C:34]([O:36][CH2:37][N:32]4[C:31](=[O:38])[CH:30]=[C:29]3[C:39]3[CH:44]=[CH:43][CH:42]=[C:41]([Cl:45])[CH:40]=3)[CH:35]=2)=[O:25])=[CH:22][CH:21]=1>C1COCC1>[Cl:45][C:41]1[CH:40]=[C:39]([C:29]2[C:28]3[C:33]4=[C:34]([O:36][CH2:37][N:32]4[C:31](=[O:38])[CH:30]=2)[CH:35]=[C:26]([C:24]([C:23]2[CH:46]=[CH:47][C:20]([Cl:19])=[CH:21][CH:22]=2)([OH:25])[C:17]2[N:13]([CH3:12])[C:14]([SH:18])=[N:15][N:16]=2)[CH:27]=3)[CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 12561623H-1,2,4-Triazole-3-thione, 2,4-dihydro-4-methyl-HCID 690419068-(4-chlorobenzoyl)-6-(3-chlorophenyl)-2H,4H-oxazolo[5,4,3-ij]quinolin-4-oneHCID 178418339Butyllithium

Product 1

HCID 178481707HCID 178481707, compoundYield 1.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

nBuLi 1.6M in hexane (0.0086 mol) was added at −78° C. to a solution of 2,4-dihydro-4-methyl-3H-1,2,4-triazole-3-thione (0.0043 mol) in THF (25 ml) under N2 flow. The mixture was stirred at 0° C. for 1 hour, then cooled to −78° C. 8-(4-chlorobenzoyl)-6-(3-chlorophenyl)-2H,4H-oxazolo[5,4,3-ij]quinolin-4-one (0.0024 mol) described in International Publication WO98/40383, was added portionwise. The mixture was stirred at room temperature for 4 hours, poured out into ice water and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (1.38 g) was purified by column chromatography over silica gel (15-40 μm) (eluent: CH2Cl2/CH3OH/NH4OH97/3/0.1). The pure fractions were collected and the solvent was evaporated. A part of the residue (0.049 g) was purified by column chromatography over silica gel (10 μm) (eluent: CH2Cl2/CH3OH 98/2). The pure fractions were collected and the solvent was evaporated, yielding 0.018 g (1%) of 6-(3-chlorophenyl)-8-[(4-chlorophenyl)hydroxy(5-mercapto-4-methyl-4H-1,2,4-triazol-3-yl)methyl]-2H,4H-oxazolo[5,4,3-ij]quinolin-4-one, melting point: 193° C. (intermediate 13).

Workup

  1. temperaturecooled to −78° C
  2. additionwas added portionwise
  3. stirringThe mixture was stirred at room temperature for 4 hours
  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 (1.38 g) was purified by column chromatography over silica gel (15-40 μm) (eluent: CH2Cl2/CH3OH/NH4OH97/3/0.1)
  10. customThe pure fractions were collected
  11. customthe solvent was evaporated
  12. customA part of the residue (0.049 g) was purified by column chromatography over silica gel (10 μm) (eluent: CH2Cl2/CH3OH 98/2)
  13. customThe pure fractions were collected
  14. customthe solvent was evaporated

Sources & evidence

ORD record
ord-4e5eaaa8ff634b9a802f73eb6b3f363e
Source dataset
uspto-grants-2008_08
Patent number
US07408063B2

Reaction notes

Loading…