Triethylamine → 7-Chloro-2-(3-methyl-2-furyl)pyrazolo[1,5-a]pyridine

Temperature

15 °C

To a solution of 2-(6-chloro-2-pyridinyl)-1-(3-methyl-2-furyl)ethanone oxime (24.5 g, 97.7 mmol) in 1,2-dimethoxyethane (200 mL) at 0° C. was added trifluoroacetic anhydride (14.5 mL, 103 mmol), while keeping the temperature below 10° C. After the addition was complete, the reaction was warmed to 15° C. The solution was then cooled to 0–5° C. and a solution of triethylamine (28.6 mL, 205 mmol) in 1,2-dimethoxyethane (30 mL) was added over 0.5 hours. The reaction mixture was allowed to warm to room temperature and was stirred for 2 hours. To this mixture was added iron(II) chloride (0.62 g, 4.9 mmol) and the reaction was heated at 75° C. for 15 hours. The reaction was concentrated, then ethyl acetate and water were added. The organic phase was separated, washed with water, dried (magnesium sulfate), filtered and concentrated. Purification by silica gel chromatography (9:1 hexanes:ethyl acetate) gave 7-chloro-2-(3-methyl-2-furyl)pyrazolo[1,5-a]pyridine (14.6 g, 640%) as yellow oil. 1H NMR (CDCl3): δ 7.52 (d, 1H), 7.48 (d, 1H), 7.10 (t, 1H), 6.92 (d, 1H), 6.86 (s, 1H), 6.42 (d, 1H), 2.49 (s, 3H). MS m/233 (M+1).

1. customthe temperature below 10° C
2. additionAfter the addition
3. temperatureThe solution was then cooled to 0–5° C.
4. temperatureto warm to room temperature
5. temperaturethe reaction was heated at 75° C. for 15 hours
6. concentrationThe reaction was concentrated
7. additionethyl acetate and water were added
8. customThe organic phase was separated
9. washwashed with water
10. dry with materialdried (magnesium sulfate)
11. filtrationfiltered
12. concentrationconcentrated
13. customPurification by silica gel chromatography (9:1 hexanes:ethyl acetate)

ORD record

ord-3d129b2d7bc947d1b2532bad0b5e36fb

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07199120B2