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

HRID 1468775

反応式

HRID 1468775 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f00d69fdc70644bc95dc5236d66b0ea7
出典データセット
uspto-grants-2015_04
特許番号
US09006232B2

関連ノート

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