Imidazole → (+/-)-4-(3-chlorophenyl)-6-[hydroxy[4-(1H-imidazol-1-ylmethyl)phenyl](1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone

HRID 346998Notes

Reaction equation

HRID 346998 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([OH:35])([C:29]2[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=2)[C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH3:20])[C:15](=[O:21])[CH:14]=[C:13]3[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)=[CH:5][CH:4]=1.[NH:36]1[CH:40]=[CH:39][N:38]=[CH:37]1.C([O-])([O-])=O.[K+].[K+].O>CC#N>[Cl:28][C:24]1[CH:23]=[C:22]([C:13]2[C:12]3[C:17](=[CH:18][CH:19]=[C:10]([C:9]([OH:35])([C:6]4[CH:7]=[CH:8][C:3]([CH2:2][N:36]5[CH:40]=[CH:39][N:38]=[CH:37]5)=[CH:4][CH:5]=4)[C:29]4[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=4)[CH:11]=3)[N:16]([CH3:20])[C:15](=[O:21])[CH:14]=2)[CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 11430Potassium CarbonateHCID 21082106(+/-)-6-[[4-(chloromethyl)phenyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4(3-chlorophenyl)-1-methyl-2(1H)-quinolinone

Product 1

HCID 21082092(+/-)-4-(3-chlorophenyl)-6-[hydroxy[4-(1H-imidazol-1-ylmethyl)phenyl](1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinoneYield 13.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (±)-6-[[4-(chloromethyl)phenyl]hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone (described in Example B14) (0.00039 mol), 1-H-imidazole (0.00079 mol) and K2CO3 (0.0016 mol) in CH3CN (2 ml) was stirred and refluxed for 4 hours, poured out into H2O and extracted with CH2Cl2. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (0.2 g) was purified twice by column chromatography over kromasil (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.5 then CH3OH/H2O 60/40; 10 μm). The pure fractions were collected and the solvent was evaporated, yielding 0.028 g (13%) of (±)-4-(3-chlorophenyl)-6-[hydroxy[4-(1H-imidazol-1-ylmethyl)phenyl](1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone, as a white foam, MS (ESI) m/z:536, 538 (MH+).

Workup

  1. temperaturerefluxed for 4 hours
  2. extractionextracted with CH2Cl2
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue (0.2 g) was purified twice by column chromatography over kromasil (eluent
  8. customThe pure fractions were collected
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-0b551b369105498ca8ab688e8659989d
Source dataset
uspto-grants-2007_02
Patent number
US07173040B2

Reaction notes

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