Methyl iodide → HCID 45110495, compound

HRID 386904Notes

Reaction equation

HRID 386904 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:10][C:11]([NH:14][C:15](=[O:28])[C:16]([CH3:27])([S:18]([CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)(=[O:20])=[O:19])[CH3:17])=[N:12][N:13]=2)=[CH:5][CH:4]=1.[H-].[Na+].[CH3:31]I>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([NH:14][C:15](=[O:28])[C:16]([CH3:17])([S:18]([CH:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)(=[O:20])=[O:19])[CH3:27])[N:12]([CH3:31])[N:13]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178489123HCID 178489123, compound

Product 1

HCID 45110495HCID 45110495, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 238 mg (0.58 mmol) of N-[5-(4-methoxy-phenyl)-4H[1,2,4]triazol-3-yl]-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide (prepared according to Amide Method A) in anhydrous THF (2 mL) at room temperature are added 94 mg (2.32 mmol) of sodium hydride (60% dispersion in mineral oil). The reaction mixture is stirred for 1 h and then 145 μL (2.32 mmol) of methyl iodide are added. The reaction is stirred at room temperature for 1 h. The reaction mixture is quenched with saturated aqueous NH4Cl solution (5 mL) and extracted with ethyl acetate (3×10 mL). The combined organic extracts are dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure. The residue is triturated with methanol and the resulting precipitate is purified by mass-directed preparative HPLC (neutral method) to afford 90 mg of N-[5-(4-methoxy-phenyl)-2-methyl-2H-[1,2,4]triazol-3-yl]-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide. Yield: 97%, ES-MS: m/z 423 [M+H].

Workup

  1. stirringThe reaction is stirred at room temperature for 1 h
  2. customThe reaction mixture is quenched with saturated aqueous NH4Cl solution (5 mL)
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts are dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated under reduced pressure
  7. customThe residue is triturated with methanol
  8. customthe resulting precipitate is purified by mass-directed preparative HPLC (neutral method)

Sources & evidence

ORD record
ord-ca98e2e764614c699936c09f433552ae
Source dataset
uspto-grants-2013_02
Patent number
US08372874B2

Reaction notes

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