Triethylamine → 7-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine

HRID 2214954Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:10]O)[CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(N(CC)CC)C>COCCOC.[Fe](Cl)Cl>[Cl:1][C:2]1[N:7]2[N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:8]=[C:6]2[CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 15 °C

Procedure

To a solution of 2-(6-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone oxime (109.2 g, 414 mmol) in 1,2-dimethoxyethane (500 mL) at 0° C. was added trifluoroacetic anhydride (59 mL, 414 mmol), keeping the temperature below 10° C. After the addition was complete, the reaction was warmed to 15° C. The solution was then cooled to 4° C. and a solution of triethylamine (116 mL 828 mmol) in 1,2-dimethoxyethane (60 mL) was added over 0.5 hours. After warming to room temperature, the mixture was stirred for 1.5 hours. To this was added iron(II) chloride (0.52 g, 4.1 mmol) and the reaction was heated to reflux for 3 hours. The reaction was concentrated and the resulting solid was recrystallized from ethyl acetate-hexanes to give 7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine (69.7 g, 68%) as off-white needles. 1H NMR (CDCl3): δ 8.03 (m, 2H), 7.54 (d, 1H), 7.16 (m, 3H), 6.93 (d, 1 H), 6.91 (s, 1H); MS m/z 247 (M+1); mp 156–157° C.

Workup

customthe temperature below 10° C
additionAfter the addition
temperatureThe solution was then cooled to 4° C.
temperatureAfter warming to room temperature
temperaturethe reaction was heated
temperatureto reflux for 3 hours
concentrationThe reaction was concentrated
customthe resulting solid was recrystallized from ethyl acetate-hexanes

Sources & evidence

ORD record: ord-91ca5079f8ff4b08bad32f43f5beeb5e
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07109209B2

Reaction notes

Loading…