反应详情

温度

-78 °C

To a stirred solution of 6-chloro-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (Preparative Example 3.1, Step 1) (1.2 g, 3.19 mmol) in THF (20 mL) was added 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex (Aldrich, 1M in THF/toluene) (5.11 mL, 5.11 mmol) at −78° C., and the reaction was stirred at −78° C. for 2 hours under a nitrogen atmosphere. 3-fluoropicolinaldehyde (1.1 g, 9.59 mmol) dissolved in THF (4.0 mL) was added dropwise at −78° C., and the reaction was stirred for an additional 2 hours at −78° C. The reaction was quenched with aqueous saturated NH4Cl solution (50 mL) and extracted with ethyl acetate (2×40 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated. Purification of the residue on a silica gel column (0 to 100% EtOAc/hexanes) afforded {6-chloro-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-2-yl}(3-fluoropyridin-2-yl)methanol. MS APCl calcd. for C25H24Cl2FN5O [M+H]+ 500. found 500.

1. additionwas added dropwise at −78° C.
2. stirringthe reaction was stirred for an additional 2 hours at −78° C
3. customThe reaction was quenched with aqueous saturated NH4Cl solution (50 mL)
4. extractionextracted with ethyl acetate (2×40 mL)
5. washThe combined organic extracts were washed with brine (20 mL)
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification of the residue on a silica gel column (0 to 100% EtOAc/hexanes)