Trifluoroacetic acid → 6-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine

Solid t-butoxycarbonyl-O-mesitylenesulfonylhydroxylamine (8.45 g 26.8 mmol) was added portionwise with stirring to TFA (100 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 (200 ml). The solution was dried over 4 Å mol. sieves for 1.5 hours, filtered and 2-(5-chloropyridin-2-yl)-1-(4-fluorophenyl)ethanone oxime (3.56 g 13.4 mmol) in chloroform (100 ml) was added. The reaction was stirred at room temperature for 18 hours, washed with water (2×50 ml) and dried. Removal of solvent gave a brown solid which was purified by Biotage chromatography. Elution with cyclohexanelethyl acetate (35/1) gave the title compound as a yellow solid (2.476 g 75%). NMR (CDCl3) δ 6.76 (1H, s, H-3); 7.08 (1H, dd, J 9 & 2 Hz, H-5); 7.13 (2H, t, J 9 Hz, H-3′); 7.45 (1H, d, J 9 Hz, H-4); 7.9 (2H, dd, J 9 & 5 Hz, H-2′); 8.5 (1H, d, J 2 Hz, H-7);

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 (200 ml)
5. customThe solution was dried over 4 Å mol
6. waitsieves for 1.5 hours
7. filtrationfiltered
8. stirringThe reaction was stirred at room temperature for 18 hours
9. washwashed with water (2×50 ml)
10. customdried
11. customRemoval of solvent
12. customgave a brown solid which
13. customwas purified by Biotage chromatography
14. washElution with cyclohexanelethyl acetate (35/1)

ORD record

ord-52d79e2295884f1cb9663fa731a8d6d9

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06498166B1