Methyl iodide → 6-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)methylamide

HRID 552169Notes

Reaction equation

HRID 552169 reaction equation
[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12]([N:15]3[CH2:20][CH2:19][CH:18]([C:21](=[O:29])[C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:17][CH2:16]3)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1.[H-].[Na+].[CH3:32]I>C1COCC1>[CH:1]1([CH2:4][CH2:5][N:6]([CH3:32])[C:7]([C:9]2[N:10]=[N:11][C:12]([N:15]3[CH2:16][CH2:17][CH:18]([C:21](=[O:29])[C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:19][CH2:20]3)=[CH:13][CH:14]=2)=[O:8])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 116253966-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide

Product 1

HCID 115460356-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)methylamideYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 6-[4-(4-fluorobenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.075 g, 0.189 mmol) and sodium hydride (0.009 g, 60% in mineral oil) in THF (15 mL) was added methyl iodide (0.134 g, 0.945 mmol) at 0° C. The reaction mixture was stirred at ambient temperature overnight, then concentrated in vacuo. The residue was diluted with water and then extracted with ethyl acetate. The organic layer was dried, concentrated and purified by column chromatography to yield the title compound in 52% yield (0.040 g). 1H NMR (300 MHz, CDCl3) δ 8.0-7.96 (m, 2H), 7.69-7.6 (m, 1H), 7.18-7.07 (m, 2H), 6.98-6.94 (m, 1H), 5.54-4.45 (m, 2H), 3.8-3.73 (m, 1H), 3.65-3.47 (m, 2H), 3.32-3.07 (m, 4H), 2.06-1.7 (m, 5H), 1.6-1.47 (m, 2H), 0.79-0.67 (m, 1H), 0.52-0.41 (m, 1H), 0.36-0.28 (m, 1H), 0.12-0.07 (m, 1H), 0.1-−0.06 (m, 1H). 13C NMR (75 MHz, CDCl3) δ 200.1, 167.5, 167.2, 166.3, 164.1, 158.8, 148.6, 148.5, 132.1, 132.07, 131.0, 130.9, 129.2, 128.9, 116.1, 115.8, 112.3, 112.2, 51.6, 49.2, 44.5, 43.2, 38.2, 34.4, 33.6, 32.0, 27.9, 8.6, 8.3, 4.3, 4.26. MS (ES+) m/z 411 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with water
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-0568e4230d1a49a0bfed37a5680f7c43
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Reaction notes

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