Dimethylformamide → HCID 18376026, compound

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).

1. additionThe solution was poured onto ice (˜250 ml)
2. filtrationThe resulting white solid was filtered off
3. washwashed with water
4. dissolutiondissolved in chloroform (100 ml)
5. customThe solution was dried over 4 Å mol
6. waitsieves for 1.5 hours
7. filtrationfiltered
8. additionadded
9. stirringstirred at ambient temperature overnight
10. concentrationAfter concentrating in vacuo
11. additionDBU (1.63 ml) added
12. stirringstirred for 18 h
13. concentrationThe mixture was concentrated
14. custompartitioned between ethyl acetate and water
15. customThe combined organic phases were dried
16. concentrationconcentrated to a brown solid which
17. customwas partially purified by SPE chromatography with cyclohexane:ethyl acetate (50:1)
18. customto give
19. temperaturecooled to 0°
20. stirringstirred for 2 h
21. extractionextracted into ethyl acetate (2×30 ml)
22. customThe resulting light brown solid was purified by SPE Si chromatography with cyclohexane:ethyl acetate (50:1) as eluant

ORD record

ord-4e44b329eb274f8286234b05f66b5ce1

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06498166B1