Dimethylformamide → HCID 18376026, compound

Participants

Reaction Steps

Solid t-butoxycarbonyl-O-mesitylenesulfonylhydroxylamine (3.16 g 10 mmol) was added portionwise with stirring to TFA (25 ml) over 10 min then stirred for a further 30 minutes. The solution was poured onto ice (˜250 ml) and left until the ice melted. The resulting white solid was filtered off, washed with water, and dissolved in chloroform (100 ml). The solution was dried over 4 Å mol. sieves for 1.5 hours, filtered, treated with 5-chloro-2-phenylethynylpyridine (1.94 g, 9 mmol) in chloroform (10 ml) added and stirred at ambient temperature overnight. After concentrating in vacuo, the resulting semisolid was suspended in MeCN (30 ml), DBU (1.63 ml) added and stirred for 18 h. The mixture was concentrated and partitioned between ethyl acetate and water. The combined organic phases were dried and concentrated to a brown solid which was partially purified by SPE chromatography with cyclohexane:ethyl acetate (50:1) to give an approximately 2:3 mixture of starting acetylene and desired cyclisation product (636 mg) (TLC SiO2 cyclohexane:ethyl acetate (3:1) Rf 0.66), which was taken up in DMF (10 ml) cooled to 0° and treated with NBS (540 mg) and allowed to warm to room temperature, stirred for 2 h then poured into water and extracted into ethyl acetate (2×30 ml). The resulting light brown solid was purified by SPE Si chromatography with cyclohexane:ethyl acetate (50:1) as eluant to give a light brown solid (565 mg). A portion of this material (100 mg) was purified by HPLC with an acetonitrile:water gradient elution to give pure title compound (40 mg). MH+ 308/309. Tlc SiO2 (cyclohexane:ethyl acetate 3:1) Rf 0.77; NMR CDCl3 δ 8.02 (1H, d, J 7 Hz); 7.5 (4H, m); 8.1 (2H, dd, J 7 & 2 Hz); 8.5 (1H, s).

Provenance & Evidence