Methyl iodide → 6-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid (2-METHOXY-3,3-DIMETHYLBUTYL)AMIDE

HRID 2056600노트

반응식

HRID 2056600 반응식
[OH:1][CH:2]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:3][NH:4][C:5]([C:7]1[N:8]=[N:9][C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:30])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])[CH2:15][CH2:14]2)=[CH:11][CH:12]=1)=[O:6].[H-].[Na+].[CH3:37]I>C1COCC1>[CH3:37][O:1][CH:2]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:3][NH:4][C:5]([C:7]1[N:8]=[N:9][C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:30])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:28])([F:29])[F:27])[CH2:15][CH2:14]2)=[CH:11][CH:12]=1)=[O:6]

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 668500126-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid (2-HYDROXY-3,3-DIMETHYLBUTYL)AMIDE

생성물 1

HCID 670122386-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid (2-METHOXY-3,3-DIMETHYLBUTYL)AMIDE수율 30.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (2-hydroxy-3,3-dimethylbutyl)amide (81.6 mg, 0.17 mmol) in THF (1.0 mL) was added sodium hydride (5.0 mg, 0.19 mmol), followed by methyl iodide (15 mL, 0.26 mmol). The reaction mixture was stirred at ambient temperature for 16 hours and then the solvent was removed. The gummy material was diluted with dichloromethane (5 mL), washed with water (2×2 mL), dried over MgSO4 and filtered off the solid. After the solvent was concentrated into dryness, the crude material was subjected to column chromatography eluted sequentially with ethyl acetate:hexane (1:1) and ethyl acetate to obtain 25.3 mg (30%) of the product as solid. m.p. 65-68° C. 1H NMR (300 MHz, CDCl3) δ 7.73-7.69, 7.62, 7.53, 7.33, 6.98-6.93, 4.18-3.59, 3.48, 3.41, 3.37-3.26, 3.18, 3.03-2.98, 1.76, 0.98, 0.75. 13C NMR (75 MHz, CDCl3) δ 167.6, 166.4, 158.9, 149.8, 149.3, 134.3, 132.4, 129.5, 129.4, 129.3, 129.1, 127.2, 126.9-126.7, 112.7, 88.1, 61.7, 61.4, 52.7, 52.0, 46.4, 44.7, 44.6, 44.5, 44.4, 41.3, 41.2, 40.5, 35.8, 35.3, 35.0, 26.0, 25.9, 25.7. MS (ES+) m/z 508 (M+1).

후처리

  1. customthe solvent was removed
  2. additionThe gummy material was diluted with dichloromethane (5 mL)
  3. washwashed with water (2×2 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered off the solid
  6. concentrationAfter the solvent was concentrated into dryness
  7. washeluted sequentially with ethyl acetate:hexane (1:1) and ethyl acetate

출처 및 근거

ORD 기록
ord-9e73233f438043c8a1ee6227965cbe83
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07335658B2

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