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

HRID 8506

반응식

HRID 8506 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][C:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:10]O)[CH:3]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(N(CC)CC)C.O>COCCOC.[Fe](Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:8]=[C:4]2[CH:3]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 738517532-(4-Chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone oxime

생성물 1

HCID 221748455-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine수율 57%

시약·촉매·용매 2

HCID 24458Ferrous Chloride촉매HCID 80711,2-Dimethoxyethane용매2회

실험 절차

To a solution of 2-(4-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone oxime (8.0 g, 30 mmol) in 1,2-dimethoxyethane (50 mL) at 0° C. was added trifluoroacetic anhydride (6.3 g, 30 mmol), keeping the temperature below 10° C. during the addition. After the addition was complete, the reaction was warmed to room temperature. The solution was then cooled to 4° C. and a solution of triethylamine (8.4 mL, 60 mmol) in 1,2-dimethoxyethane (20 mL) was added over a period of 0.5 hours. The mixture was allowed to warm to room temperature and was stirred for 1.5 hours. To this mixture was added iron(II) chloride (40 mg) and the reaction was heated at 75° C. for 15 hours. The reaction mixture was poured into water (300 mL). The resulting suspension was extracted with ethyl acetate. The combined organics were dried (magnesium sulfate), filtered and concentrated to a solid residue. This residue was purified by flash chromatography (1:1 ethyl acetate-hexane) to give 5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine (4.2 g, 57 %) as a white solid. 1H-NMR (CDCl3): δ 8.36 (d, 1H), 7.93 (q, 2H), 7.49 (d, 1H), 7.15 (t, 2H), 6.70 (dd, 1H), 6.69 (s, 1H); 19F-NMR (CDCl3): δ −113.30; MS m/z 247 (M+1).

후처리

  1. customthe temperature below 10° C.
  2. additionduring the addition
  3. additionAfter the addition
  4. temperatureThe solution was then cooled to 4° C.
  5. temperatureto warm to room temperature
  6. temperaturethe reaction was heated at 75° C. for 15 hours
  7. extractionThe resulting suspension was extracted with ethyl acetate
  8. dry with materialThe combined organics were dried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated to a solid residue
  11. customThis residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

출처 및 근거

ORD 기록
ord-0dd7b29960b94ef1aaca212f5b05d9dd
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07087618B2

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