2-(tert-Butyldimethylsilyl)-1-methyl-1H-imidazole → 6-[[2-(tert-Butyl-dimethyl-silanyl)-3-methyl-3H-imidazol-4-yl]-(4-chloro-phenyl)-hydroxy-methyl]-1-cyclopropylmethyl-4-(3-trimethylsilanylethynyl-phenyl)-1H-quinolin-2-one

HRID 1597481Notes

Reaction equation

HRID 1597481 reaction equation
[C:1]([Si:5]([CH3:13])([CH3:12])[C:6]1[N:7]([CH3:11])[CH:8]=[CH:9][N:10]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])(CC)C.[Cl:19][C:20]1[CH:54]=[CH:53][C:23]([C:24]([C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[N:32]([CH2:36][CH:37]2[CH2:39][CH2:38]2)[C:31](=[O:40])[CH:30]=[C:29]3[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[C:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[CH:42]=2)=[O:25])=[CH:22][CH:21]=1>C1COCC1>[C:1]([Si:5]([CH3:13])([CH3:12])[C:6]1[N:7]([CH3:11])[C:8]([C:24]([C:23]2[CH:53]=[CH:54][C:20]([Cl:19])=[CH:21][CH:22]=2)([OH:25])[C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[N:32]([CH2:36][CH:37]2[CH2:39][CH2:38]2)[C:31](=[O:40])[CH:30]=[C:29]3[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([C:47]#[C:48][Si:49]([CH3:51])([CH3:52])[CH3:50])[CH:42]=2)=[CH:9][N:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 45472442-(tert-Butyldimethylsilyl)-1-methyl-1H-imidazoleHCID 185164466-(4-Chloro-benzoyl)-1-cyclopropylmethyl-4-(3-trimethylsilanylethynyl-phenyl)-1H-quinolin-2-oneHCID 178418400CID 53628100

Product 1

HCID 185164406-[[2-(tert-Butyl-dimethyl-silanyl)-3-methyl-3H-imidazol-4-yl]-(4-chloro-phenyl)-hydroxy-methyl]-1-cyclopropylmethyl-4-(3-trimethylsilanylethynyl-phenyl)-1H-quinolin-2-oneYield 93.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-(tert-butyl-dimethyl-silanyl)-1-methyl-1H-imidazole (1.71 g, 8.7 mmol) in THF (40 mL) at −78° C. was treated with sec-butyllithium (1.3 M in cyclohexane, 8.4 mL, 10.9 mmol). The reaction mixture was warmed to 0° C., stirred for 3 hours, and cooled to −78° C. A solution of 6-(4-Chloro-benzoyl)-1cyclopropylmethyl-4-(3-trimethylsilanylethynyl-phenyl)-1H-quinolin-2-one (3.47 g, 6.8 mmol) (2.87 g, 6.4 mmol) in THF (20 mL) was cannulated into the reaction mixture, slowly warmed to room temperature, and stirred overnight. The reaction mixture was quenched with ammonium chloride (12 mL), diluted with ether (200 mL), and washed with H2O (200 mL) and brine (200 mL). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo to give 6-[[2-(tert-Butyl-dimethyl-silanyl)-3-methyl-3H-imidazol-4-yl]-(4-chloro-phenyl)-hydroxy-methyl]-1-cyclopropylmethyl-4-(3-trimethylsilanylethynyl-phenyl)-1H-quinolin-2one (4.50 g) as a yellow foam. The crude material was used in the next step without any further purification.

Workup

  1. temperaturecooled to −78° C
  2. temperatureslowly warmed to room temperature
  3. stirringstirred overnight
  4. customThe reaction mixture was quenched with ammonium chloride (12 mL)
  5. additiondiluted with ether (200 mL)
  6. washwashed with H2O (200 mL) and brine (200 mL)
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e5f9deaf9d354d07ab6eb1e0a85fd2f1
Source dataset
uspto-grants-2001_09
Patent number
US06294552B1

Reaction notes

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