Trifluoromethanesulfonic anhydride → 2-Benzyloxy-4-[5-(5-chloro-2-oxo-2H-[1,2']bipyridinyl-5'-ylmethyl)-imidazol-1-ylmethyl]-benzonitrile

Temperature

-78 °C

To a cooled solution (-78° C.) of 2-benzyloxy-4-hydroxymethyl-benzonitrile from step 2 (100 mg, 0.42 mmol) and 5-chloro-5'-(1-trityl-1H-imidazol-4-ylmethyl)-[1,2']bipyridinyl-2-one from Example 23, Step 5 (221 mg, 0.42 mmol) in CH2Cl2 (2.1 ml) was added DIEA (325 μl, 0.92 mmol) followed immediately by the addition of Tf2O (160 μl, 0.63 mmol). The reaction mixture was stirred at -78° C. for 1 hour and was then transferred to an ice bath and stirred at 0° C. for another hour. The solvent was removed in vacuo. The residue was then dissolved in MeOH and heated to 60° C. for several hours. The MeOH was then removed in vacuo and the residue treated with saturated NaHCO3 (5 mL) and extracted with CH2Cl2 (2×10 mL). The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography [4% MeOH(5% NH4OH)/CH2Cl2 ] to yield the final product.

1. customwas then transferred to an ice bath
2. stirringstirred at 0° C. for another hour
3. customThe solvent was removed in vacuo
4. dissolutionThe residue was then dissolved in MeOH
5. temperatureheated to 60° C. for several hours
6. customThe MeOH was then removed in vacuo
7. additionthe residue treated with saturated NaHCO3 (5 mL)
8. extractionextracted with CH2Cl2 (2×10 mL)
9. washThe organic layer was washed with brine
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue was purified by flash chromatography [4% MeOH(5% NH4OH)/CH2Cl2 ]

ORD record

ord-6a692a27f7d349c7b5a3799b2a396f3d

Source dataset

uspto-grants-2000_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06077853