Trifluoroacetic acid → 1-methyl-2-(piperidin-4-yloxy)-1H-[4,4']bipyrimidinyl-6-one

HRID 1468775

반응식

HRID 1468775 반응식
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6][CH2:5]1.Cl[C:18]1[N:19]([CH3:31])[C:20](=[O:30])[CH:21]=[C:22]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][N:25]=2)[N:23]=1.FC(F)(F)C(O)=O>O1CCCC1.ClCCl>[CH3:31][N:19]1[C:20](=[O:30])[CH:21]=[C:22]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][N:25]=2)[N:23]=[C:18]1[O:3][CH:4]1[CH2:5][CH2:6][NH:7][CH2:8][CH2:9]1

참가 물질

7

반응물 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 179544602-Chloro-3-methyl-6-(pyrimidin-4-YL)pyrimidin-4-one

생성물 1

HCID 679776501-methyl-2-(piperidin-4-yloxy)-1H-[4,4']bipyrimidinyl-6-one수율 47%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of sodium hydride (60 wt % in mineral oil, 0.772 g, 19.3 mmol) in tetrahydrofuran (92 ml) was added tert-butyl 4-hydroxy-piperidine-1-carboxylate (3.70 g, 18.4 mmol) at 0° C. The mixture was stirred at room temperature for one hour, then 2-chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (4.09 g, 18.4 mmol) was added. The mixture was stirred overnight. The mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was dissolved into dichloromethane (37 ml), and trifluoroacetic acid (41.9 g, 368 mmol) was added to the solution. The mixture was stirred at room temperature for 5 hours. After concentration under reduced pressure, the residue was dissolved into water. The aqueous solution was washed with ethyl acetate and basified with potassium carbonate. Extraction with chloroform was performed three times. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford 1-methyl-2-(piperidin-4-yloxy)-1H-[4,4′]bipyrimidinyl-6-one as a pale yellow solid (2.48 g, 8.63 mmol, 47%). This compound was used for the next reaction without further purification.

후처리

  1. stirringThe mixture was stirred overnight
  2. customThe mixture was partitioned between water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. additionwas added to the solution
  7. stirringThe mixture was stirred at room temperature for 5 hours
  8. concentrationAfter concentration under reduced pressure
  9. dissolutionthe residue was dissolved into water
  10. washThe aqueous solution was washed with ethyl acetate
  11. extractionExtraction with chloroform
  12. dry with materialThe organic layer was dried over sodium sulfate
  13. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-f00d69fdc70644bc95dc5236d66b0ea7
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006232B2

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