Methyl iodide → HCID 21934287, compound

HRID 381973Notes

Reaction equation

HRID 381973 reaction equation
[OH:1][CH:2]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[C:7]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[CH:6]=[N:5]1.I[CH3:35].[H-].[Na+]>CN(C=O)C>[CH3:35][O:1][CH:2]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[CH2:3][N:4]1[C:9](=[O:10])[C:8]([C:11]2[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=2)=[C:7]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[CH:6]=[N:5]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 21933843HCID 21933843, compound

Product 1

HCID 21934287HCID 21934287, compoundYield 34.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the product from Example 441, 2-(2-hydroxy-2-phenylethyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (210 mg, 0.45 mmol), iodomethane (56 μL, 0.90 mmol), and an 80% oil dispersion of sodium hydride (18 mg, 0.59 mmol) in anhydrous DMF (16 mL) was stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and 2 N aqueous hydrochloric acid. The organic layer was washed with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to provide a yellow oil which was purified by column lo chromatography (silica gel, 70:30 hexanes/ethyl acetate). Fractions containing product were combined and concentrated in vacuo , and the residue was triturated with hexanes to provide the title compound (yield: 75 mg, 34.7%). mp 135-137° C. 1H NMR (300 MHz, CDCl3) δ 3.07 (s, 3H), 3.26 (s, 3H), 4.33-4.52 (m, 2H), 4.91 (dd, J=9 Hz, 3 Hz, 1H), 6.99 (t, J=9 Hz, 2H), 7.20 (dd, J=9 Hz, 3 Hz, 2H), 7.31-7.50 (m, 7H), 7.87 (s, 1H), 7.89 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 479 (M+H)+. Anal. calc. for C26H23FN2O4S: C, 65.25; H, 4.84; N, 5.85. Found: C, 64.98; H, 4.83; N, 5.81.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and 2 N aqueous hydrochloric acid
  2. washThe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto provide a yellow oil which
  7. customwas purified by column lo chromatography (silica gel, 70:30 hexanes/ethyl acetate)
  8. additionFractions containing product
  9. concentrationconcentrated in vacuo
  10. customthe residue was triturated with hexanes

Sources & evidence

ORD record
ord-2cc0c1375709446bb26db9ca3c9f9df1
Source dataset
uspto-grants-2001_10
Patent number
US06307047B1

Reaction notes

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