Potassium Hydroxide → 6-Fluoro-4-iodo-N-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)pyridin-3-amine

HRID 1640908노트

반응식

HRID 1640908 반응식
OC(C(F)(F)F)=O.[F:8][C:9]1[N:14]=[CH:13][C:12]([NH2:15])=[C:11]([I:16])[CH:10]=1.Br[CH2:18][CH2:19][O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1.[OH-].[K+].[F-].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[F:8][C:9]1[N:14]=[CH:13][C:12]([NH:15][CH2:18][CH2:19][O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)=[C:11]([I:16])[CH:10]=1

참가 물질

7

반응물 4

HCID 14797Potassium HydroxideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 522689Potassium FluorideHCID 866418746-fluoro-4-iodopyridin-3-amine TFA salt

생성물 1

HCID 667381816-Fluoro-4-iodo-N-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)pyridin-3-amine수율 66%

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

Mix 6-fluoro-4-iodopyridin-3-amine TFA salt (0.36 g, 1.50 mmol), 2-[(2-bromoethyl)oxy]tetrahydro-2H-pyran (1.38 g, 6.60 mmol), potassium hydroxide (0.19 g, 3.30 mmol), potassium fluoride (0.19 g, 3.30 mmol), and tetrabutylammonium iodide (0.11 g, 0.3 mmol) in 1,4-dioxane (1.5 mL) in a seal reactor. Heat the reaction mixture at 100° C. overnight. Cool the reaction mixture to RT. Quench with water. Extract with ethyl acetate, wash the organic layer with water and saturated aqueous sodium chloride. Dry over MgSO4. After filtration, concentrate and purify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2) to give the title compound (0.36 g, 66%) with 100% HPLC purity. MS (ES) m/z 367 [M+1]+.

후처리

  1. temperatureCool the reaction mixture to RT
  2. customQuench with water
  3. extractionExtract with ethyl acetate
  4. washwash the organic layer with water and saturated aqueous sodium chloride
  5. dry with materialDry over MgSO4
  6. filtrationAfter filtration
  7. concentrationconcentrate
  8. custompurify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2)

출처 및 근거

ORD 기록
ord-f070a66297674ab3b0d16f512f3a6f97
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08114872B2

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