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

HRID 2356579Notes

Reaction equation

HRID 2356579 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-ae25dc50ff2343a49f6ea456bd0616ab
Source dataset
uspto-grants-2010_07
Patent number
US07759348B2

Reaction notes

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