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

Temperatur

0 °C

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)-1-cyclopropylmethyl-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-cyclopropylmethyl4-(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.

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

ORD-Eintrag

ord-a8cf6d288b6d4e3f9b626c890839b401

Quelldatensatz

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06579887B2