Diisopropylamine → HCID 23503252, compound

Participants

Reaction Steps

A solution of butyl lithium in hexanes (2.5M, 1.3 ml) was added to a solution of diisopropylamine (0.45 ml) in tetrahydrofuran (6 ml) at 0° C. under nitrogen. After 30 minutes, 5 ml of the resulting solution was added to a solution of 5-methyl-7-(2-methylpropyl)-2-phenylmethylthieno[2,3-d]pyridazin-4(5H)-one (example 15, 0.50 g) and S-[3-{[(1,1-dimethylethyl)dimethylsilyl]oxy}propyl] 4methylbenzenesulfonothioate, (J. Med. Chem. 1995, 38, 2557., 0.85 g) in tetrahydrofuran (10 ml) at −78° C. under nitrogen. The reaction mixture was warmed to room temperature, quenched with saturated aqueous ammonium chloride solution (25 ml) and extracted with ethyl acetate (50 ml). The organic extracts were washed twice with saturated aqueous ammonium chloride solution, twice with saturated sodium hydrogen carbonate solution, then with brine, dried, filtered and evaporated. The residue was dissolved in acetonitrile (20 ml) and treated with 40% hydrofluoric acid (1 ml). After 16 hours, saturated sodium hydrogen carbonate solution (50 ml) was added and the mixture was extracted with ethyl acetate (50 ml). The organic extracts were washed with brine, dried, filtered and evaporated. The residue was purified by column chromatography, eluting with ethyl acetate:isohexane (1:2 then 1:1) to give the title compound (0.51 g) as a solid.

Provenance & Evidence