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

HRID 2354812ノート

反応式

HRID 2354812 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7b5e3d5aed244d1fa8e90227b4df3c52
出典データセット
uspto-grants-2010_07
特許番号
US07754711B2

反応ノート

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