Methyl iodide → HCID 56602953, compound

HRID 1809435Notes

Reaction equation

HRID 1809435 reaction equation
[OH:1][CH2:2][C:3]([C:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:26])[C:13]([CH3:25])([S:15]([CH2:18][CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)(=[O:17])=[O:16])[CH3:14])[O:8][N:7]=1)([CH3:5])[CH3:4].[H-].[Na+].[CH3:29]I>C1COCC1>[CH3:29][O:1][CH2:2][C:3]([C:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:26])[C:13]([CH3:14])([S:15]([CH2:18][CH:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)(=[O:17])=[O:16])[CH3:25])[O:8][N:7]=1)([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 45256132HCID 45256132, compound

Product 1

HCID 56602953HCID 56602953, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of 70 mg (0.18 mmol) of N-[3-(2-hydroxy-1,1-dimethyl-ethyl)-isoxazol-5-yl]-2-methyl-2-(tetrahydro-pyran-4-ylmethanesulfonyl)-propionamide in anhydrous THF (2 mL) at 5° C. are added 9 mg (0.36 mmol) of sodium hydride (60% dispersion in mineral oil). The reaction mixture is stirred for 0.5 h and then 32 μL (0.54 mmol) of methyl iodide are added. The reaction is stirred at room temperature for 18 h and is then warmed to 35° C. for 6 h. The reaction is quenched by addition of methanol and concentrated under reduced pressure. The residue is dissolved in DCM and washed with water, saturated aqueous NaHCO3 solution and brine. The organic layer is dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography (silica, eluent: DCM, 10% ethyl acetate) followed by preparative HPLC (neutral conditions) to afford 20 mg of N-[3-(2-methoxy-1,1-dimethyl-ethyl)-isoxazol-5-yl]-2-methyl-2-(tetrahydro-pyran-4-ylmethanesulfonyl)-propionamide. Yield: 28%, ES-MS: m/z 403 [M+H]

Workup

  1. stirringThe reaction is stirred at room temperature for 18 h
  2. customThe reaction is quenched by addition of methanol
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue is dissolved in DCM
  5. washwashed with water, saturated aqueous NaHCO3 solution and brine
  6. dry with materialThe organic layer is dried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate is concentrated under reduced pressure
  9. customThe residue is purified by column chromatography (silica, eluent: DCM, 10% ethyl acetate)

Sources & evidence

ORD record
ord-8e6bab8ab5504e07998555a2cb871c75
Source dataset
uspto-grants-2013_01
Patent number
US08362039B2

Reaction notes

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