反应详情

Magnesium (0.317 g, 12.03 mmol) was flame dried in a 50 mL RB flask equipped with addition funnel and magnetic stirrer under N2. When the flask had cooled, anhydrous THF (3 mL), a pinch of iodine, and a THF solution of Rieke magnesium (1 mL) were added, followed by a small portion of (3-bromopropoxy)-tert-butyldimethylsilane (3.048 g, 12.03 mmol) in THF (5 mL) with slight warming to initiate the reaction. The remainder of the bromide solution was added dropwise over 15 min. After 15 min. this Grignard solution was added to a solution of N-[(4-cyano-3-fluoro-phenyl)-(3-methyl-3H-imidazol-4-yl)-methylene]-2-methylpropanesulfinamide (Example 1, Step G) (1.00 g, 3.01 mmol) in THF (5 mL) with cooling in an ice-H2O bath. After 5 mL of Grignard solution was consumed, the reaction was complete by HPLC. The reaction mixture was quenched with H2O, diluted with saturated NaHCO3 solution and extracted with CH2Cl2 (2×20 mL). The organic layers were combined, washed with brine, dried (MgSO4), filtered and concentrated to give the crude product. Purification on an ISCO Combiflash eluting with 1-3% MeOH/CH2Cl2 w/NH4OH gave the title compound.

1. customdried in a 50 mL RB flask
2. customequipped with addition funnel and magnetic stirrer under N2
3. temperatureWhen the flask had cooled
4. additionanhydrous THF (3 mL), a pinch of iodine, and a THF solution of Rieke magnesium (1 mL) were added
5. temperaturewith slight warming
6. customthe reaction
7. temperaturewith cooling in an ice-H2O bath
8. customAfter 5 mL of Grignard solution was consumed
9. customThe reaction mixture was quenched with H2O
10. additiondiluted with saturated NaHCO3 solution
11. extractionextracted with CH2Cl2 (2×20 mL)
12. washwashed with brine
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. concentrationconcentrated
16. customto give the crude product
17. customPurification on an ISCO Combiflash
18. washeluting with 1-3% MeOH/CH2Cl2