HCID 22721256, compound → HCID 178481121, compound

HRID 1582403Notes

Reaction equation

HRID 1582403 reaction equation
[SH:1][C:2]1[N:3]([CH3:7])[CH:4]=[CH:5][N:6]=1.C([Li])(C)(C)C.[Cl:13][C:14]1[CH:45]=[CH:44][C:17]([C:18]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]([CH3:30])[C:25](=[O:31])[CH:24]=[C:23]3[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Si:38]([CH3:41])([CH3:40])[CH3:39])[C:33]=2[C:42]#[CH:43])=[O:19])=[CH:16][CH:15]=1>C1COCC1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]([OH:19])([C:4]2[N:3]([CH3:7])[C:2]([SH:1])=[N:6][CH:5]=2)[C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]([CH3:30])[C:25](=[O:31])[CH:24]=[C:23]3[C:32]2[CH:33]=[CH:42][CH:43]=[C:36]([C:35]#[C:34][Si:38]([CH3:41])([CH3:39])[CH3:40])[CH:37]=2)=[CH:44][CH:45]=1

Participants

5

Reactant 3

HCID 22721256HCID 22721256, compoundHCID 178418306HCID 178418306, compoundHCID 178480602HCID 178480602, compound

Product 1

HCID 178481121HCID 178481121, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-Mercapto-1-methylimidazole (2.08 g, 18.2 mMol) was dissolved in anhydrous THF (200 mL) under an atmosphere of dry N2. The solution was cooled to −78° C. and a solution of tert-butyl lithium (1.7 M in pentane, 22 mL, 37 mMol) was added. The solution was then warmed to 0° C. After a yellow precipitate formed, the solution was cooled to −78° C. and a solution of 6-(4-chloro-benzoyl)-1-methyl-4-(3-trimethylsilanyl ethynyl-phenyl)-1H-quinolin-2-one (8.55 g, 18.2 mMol) in anhydrous THF (25 mL) was added. After 30 minutes, the solution was warmed to 0° C. and stirred at this temperature for 1 hour. The reaction mixture was then warmed to ambient temperature and stirred overnight. The reaction was quenched with 20 mL of saturated aqueous ammonium chloride (NH4Cl) and then partitioned between DCM and water. The DCM layer was dried over sodium sulfate (Na2SO4), filtered and concentrated under vacuum. The residue was chromatographed on flash silica gel eluting with a gradient from DCM to MeOH/DCM (3:97) to give 5.0 g of the titled compound as a solid.

Workup

  1. temperatureThe solution was then warmed to 0° C
  2. customAfter a yellow precipitate formed
  3. temperaturethe solution was cooled to −78° C.
  4. temperaturethe solution was warmed to 0° C.
  5. temperatureThe reaction mixture was then warmed to ambient temperature
  6. stirringstirred overnight
  7. customThe reaction was quenched with 20 mL of saturated aqueous ammonium chloride (NH4Cl)
  8. custompartitioned between DCM and water
  9. dry with materialThe DCM layer was dried over sodium sulfate (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customThe residue was chromatographed on flash silica gel eluting with a gradient from DCM to MeOH/DCM (3:97)

Sources & evidence

ORD record
ord-4887586b1b1f4c6b91c9e8a2e03c5184
Source dataset
uspto-grants-2004_05
Patent number
US06734308B2

Reaction notes

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