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

HRID 1640908ノート

反応式

HRID 1640908 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-f070a66297674ab3b0d16f512f3a6f97
出典データセット
uspto-grants-2012_02
特許番号
US08114872B2

反応ノート

読み込み中…