Sodium hydride → N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine

HRID 1045912

반응식

HRID 1045912 반응식
[H-].[Na+].[CH3:3][N:4]1[CH:8]=[C:7]([NH:9][C:10](=O)[CH3:11])[C:6]([CH3:13])=[N:5]1.ClC1C=[C:19]([I:21])[C:18]([C:22]([F:25])([F:24])[F:23])=[CH:17][N:16]=1.O.[OH-].[Li+]>C1COCC1.O>[CH3:3][N:4]1[CH:8]=[C:7]([NH:9][C:10]2[CH:11]=[C:19]([I:21])[C:18]([C:22]([F:25])([F:24])[F:23])=[CH:17][N:16]=2)[C:6]([CH3:13])=[N:5]1

참가 물질

7

반응물 4

HCID 24758Sodium hydrideHCID 168937Lithium hydroxide, monohydrateHCID 27737912-Chloro-4-iodo-5-(trifluoromethyl)pyridineHCID 19346285N-(1,3-dimethylpyrazol-4-yl)acetamide

생성물 1

HCID 56951658N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine수율 46.8%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

Sodium hydride (1.732 g, 41.13 mmol) was added to N-(1,3-dimethylpyrazol-4-yl)acetamide (6.3 g, 41.1 mmol) dissolved in THF (80 mL) under nitrogen. The resulting light suspension was stirred at room temperature for 15 minutes then at 35° C. for 15 minutes and then 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (6.02 g, 19.6 mmol) was added. The mixture was stirred at 35° C. for 20 minutes then at 45° C. for 30 minutes, giving a light purple solution. The resulting mixture was allowed to cool to room temperature, quenched with water (30 mL) and lithium hydroxide hydrate (2.466 g, 58.75 mmol) was added. The mixture was stirred at room temperature for 1.5 hours. The mixture was extracted twice with DCM. The combined organic phases were washed with water, brine, dried over magnesium sulfate and concentrated to afford the crude product. The crude product was purified by flash chromatography on silica gel eluting with 0 to 50% EtOAc in DCM. The fractions containing pure product were evaporated to dryness, sonicated in petroleum ether then collected by filtration, washed with petroleum ether and dried to a constant weight to afford N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (3.5 g, 9.16 mmol, 46.8%) as a white solid.

후처리

  1. waitat 35° C. for 15 minutes
  2. stirringThe mixture was stirred at 35° C. for 20 minutes
  3. waitat 45° C. for 30 minutes
  4. customgiving a light purple solution
  5. temperatureto cool to room temperature
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature for 1.5 hours
  8. extractionThe mixture was extracted twice with DCM
  9. washThe combined organic phases were washed with water, brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated
  12. customto afford the crude product
  13. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 50% EtOAc in DCM
  14. additionThe fractions containing pure product
  15. customwere evaporated to dryness
  16. customsonicated in petroleum ether
  17. filtrationthen collected by filtration
  18. washwashed with petroleum ether
  19. customdried to a constant weight

출처 및 근거

ORD 기록
ord-4cafc50ef4e54976a8ecab9274ae211a
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569298B2

연결된 노트

불러오는 중…