1-Methylimidazole → HCID 10183987, compound

HRID 1827266Notes

Reaction equation

HRID 1827266 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.Cl[Si](CC)(CC)CC.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([C:29]2[CH:30]=[C:31]3[C:36](=[CH:37][CH:38]=2)[N:35]=[C:34]([CH3:39])[N:33]=[C:32]3[C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[CH:41]=2)=[O:28])=[CH:23][CH:22]=1>C1COCC1>[Cl:46][C:42]1[CH:41]=[C:40]([C:32]2[C:31]3[C:36](=[CH:37][CH:38]=[C:29]([C:27]([C:24]4[CH:23]=[CH:22][C:21]([Cl:20])=[CH:26][CH:25]=4)([C:11]4[N:7]([CH3:6])[CH:8]=[N:9][CH:10]=4)[OH:28])[CH:30]=3)[N:35]=[C:34]([CH3:39])[N:33]=2)[CH:45]=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 22136465HCID 22136465, compoundHCID 178418339Butyllithium2×

Product 1

HCID 10183987HCID 10183987, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

BuLi (2.9 ml;0.0046 mol) was added dropwise at −70° C. to a solution of 1-methyl-1H-imidazole (0.0046 mol) in THF (7 ml) under N2 flow. The mixture was stirred at −70° C. for 15 min. Chlorotriethyl-silane (0.0048 mol) was added. The mixture was stirred at −70° C. for 15 min. n BuLi (2.6 ml;0.0041 mol) was added dropwise. The mixture was stirred at −70° C. for 15 min. A solution of intermediate (4) (0.00264 mol) obtained in Example A2, in THF (20 ml) was added dropwise at −70° C. The mixture was stirred at −70° C. for 1 hour, poured out into ice water and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (2.1 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH; 95/5/0.2; 15–40 μm). The pure fractions were collected and the solvent was evaporated. The residue (0.59 g) was crystallized from diethylether. The precipitate was filtered off and dried, yielding 0.49 g (40%) of 4-(3-chlorophenyl)-α-(4-chlorophenyl)-2-methyl-α-(1-methyl-1H-imidazol-5-yl)-6-quinazolinemethanol, mp. 223° C.

Workup

  1. additionwas added dropwise
  2. stirringThe mixture was stirred at −70° C. for 15 min
  3. stirringThe mixture was stirred at −70° C. for 1 hour
  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 (2.1 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH; 95/5/0.2; 15–40 μm)
  10. customThe pure fractions were collected
  11. customthe solvent was evaporated
  12. customThe residue (0.59 g) was crystallized from diethylether
  13. filtrationThe precipitate was filtered off
  14. customdried

Sources & evidence

ORD record
ord-92f260d024094b71853b6319d1a6fd1c
Source dataset
uspto-grants-2006_05
Patent number
US07053105B2

Reaction notes

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