Sodium hydride → 4-[5-(4-Methoxy-phenyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2264437노트

반응식

HRID 2264437 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:18]1[N:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[CH:20][N:19]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:18]2[N:19]=[CH:20][C:21]([C:24]3[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=3)=[CH:22][N:23]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 12682914-Amino-1-Boc-piperidineHCID 27610202-Chloro-5-(4-methoxyphenyl)pyrimidine

생성물 1

HCID 687810944-[5-(4-Methoxy-phenyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester수율 9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.0 g, 20.0 mmol, 1.3 equiv; commercially available) in dry DMF (100 mL) under Ar was added sodium hydride (1.01 g, 23.1 mmol, 1.5 equiv; 55% free-flowing powder moistened with oil) and the reaction mixture stirred at rt. After 2 h 2-chloro-5-(4-methoxy-phenyl)-pyrimidine (3.39 g, 15.4 mmol, 1.0 equiv; commercially available from Peakdale Molecular, UK) was added and the mixture stirred at rt for 48 h. The solvent was removed under reduced pressure and the crude reaction product extracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate to provide 0.55 g (9%) of the title compound. MS (ISP): 385.4 [M+H]+.

후처리

  1. additioncommercially available from Peakdale Molecular, UK) was added
  2. stirringthe mixture stirred at rt for 48 h
  3. customThe solvent was removed under reduced pressure
  4. customthe crude reaction product
  5. extractionextracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customthe crude material purified by silica column chromatography
  9. washeluting with a gradient of heptane/ethyl acetate

출처 및 근거

ORD 기록
ord-a16bd2679b724e87bd275d72c9187de1
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855194B2

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