1-Methylimidazole → HCID 9933347, compound

Temperature

-78 °C

To a solution of 1-methylimidazole (53 mg) in anhydrous THF (3 mL) was added dropwise a solution of butyllithium in hexane (1.6 M, 430 μL) at about −78° C. The mixture was stirred at about −78° C. for about 15 minutes. To the solution was added dropwise a solution of chlorotriethylsilane in THF (1.0M, 660 μL). The mixture was warmed to room temperature and stirred at room temperature for 1 hour. The mixture was cooled to about −78° C. and to it was added dropwise a solution of butyllithium in hexane (1.6M, 430 μL). The solution was stirred at about −78° C. for about 1 hour and in the following 15 minutes, it was warmed to about −15° C. The solution was cooled to about −78° C. To it was added dropwise a solution of 1-methylsulfonyl-3-(3-chlorophenyl)-5-(4-chlorobenzoyl)indole (95 mg) (see preparation #7) in THF (2 mL). The mixture was warmed to room temperature and stirred for about 2 hours. The solution was cooled to about 0° C. and to it was added methanol and water. The mixture was stirred for about 2 hours. The solution was concentrated in vacuo. The residue was dissolved in dichloromethane (DCM) and washed with water once. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography, on silica, eluting with DCM/MeOH 95:5. Affording the title compound Rf=0.20 (silica, DCM/MeOH 9:1), MS (ES) 447.2; Calc. MW=447.4. 60 mg, yield: 63%.

1. temperatureThe mixture was warmed to room temperature
2. stirringstirred at room temperature for 1 hour
3. temperatureThe mixture was cooled to about −78° C. and to it
4. stirringThe solution was stirred at about −78° C. for about 1 hour and in the following 15 minutes, it
5. temperaturewas warmed to about −15° C
6. temperatureThe solution was cooled to about −78° C
7. temperatureThe mixture was warmed to room temperature
8. stirringstirred for about 2 hours
9. temperatureThe solution was cooled to about 0° C. and to it
10. stirringThe mixture was stirred for about 2 hours
11. concentrationThe solution was concentrated in vacuo
12. dissolutionThe residue was dissolved in dichloromethane (DCM)
13. washwashed with water once
14. dry with materialThe organic layer was dried over anhydrous MgSO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe crude product was purified by column chromatography, on silica
18. washeluting with DCM/MeOH 95:5

ORD record

ord-3c1b81c6f5eb4747a0a1621b384bd978

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06420555B1