4-Iodopyridine → HCID 57978151, compound

Participants

Reaction Conditions

Reaction Steps

tert-Butyllithium (1.5 M solution in pentane, 2.15 mL) was diluted with anhydrous THF (10 mL) at −100° C. under an atmosphere of argon. To this was added dropwise a solution of 4-iodopyridine (330 mg, 1.773 mmol) in anhydrous THF (8 ml,), the mixture was stirred at −100° C. for 5 min and then a solution of N-[(1E)-(3-bromophenyl)(2-cyanopyridin-3-yl)methylene]-2-methylpropane-2-sulfinamide (Example 2, 629 mg, 1.612 mmol) in THF (10 mL) was added dropwise while maintaining the temperature at or below −100° C. The mixture was stirred for 1.5 h during which time it was allowed to warm up to −75° C. The reaction was quenched by the addition of water and the mixture was diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium hydrogen carbonate and brine, then dried over magnesium sulfate and evaporated. The residue was dissolved in methanol (10 mL) and treated with 2 M hydrochloric acid in diethyl ether overnight at room temperature. The solvents were evaporated and the residue was taken up with saturated aqueous hydrogen carbonate and dichloromethane. The phases were separated, the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated. Purification by column chromatography using a gradient of increasing concentration of 2 M methanolic ammonia in dichloromethane (from 0 to 5%) gave 406 mg (69% yield) of the title compound. 1H NMR (CDCl3) δ 8.67 (dd, 1H), 8.53 (m, 2H), 7.90 (dd, 1H), 7.41 (m, 3H), 7.23 (m, 3H), 7.18 (m, 1H); MS (ESI) m/z 365, 367 [M+1]+.

Provenance & Evidence