Methyl iodide → [4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-methyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

HRID 1966971Notes

Reaction equation

HRID 1966971 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]([N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH2:15][CH2:14]1)=[O:12].[H-].[Na+].I[CH3:31]>CN(C)C=O>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]([N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]([CH3:31])[CH2:15][CH2:14]1)=[O:12]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 53311864[4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Product 1

HCID 53311865[4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-methyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanoneYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 0.12 g (0.30 mmol) [4-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (Example 3) in 1 mL N,N-dimethylformamide was treated with 0.014 g (0.32 mmol) sodium hydride (60% suspension in mineral oil) upon which gas evolution set in and a colour change occurred. After stirring for 30 min., 0.022 mL (0.36 mmol) iodomethane were added. After stirring for 7 hours at room temperature, the reaction mixture was poured onto water and was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated to dryness. The resulting powder was purified by silica gel chromatography using a MPLC system (20 g silica gel column, CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50) to give the desired compound as an orange solid (32 mg, 26%). MS (ESI): m/z=414.077 [M+H]+.

Workup

  1. stirringAfter stirring for 7 hours at room temperature
  2. additionthe reaction mixture was poured onto water
  3. extractionwas extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. additiontreated with silica gel
  8. customevaporated to dryness
  9. customThe resulting powder was purified by silica gel chromatography
  10. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50)

Sources & evidence

ORD record
ord-52b80fdfe4d84dcca29a178b4e67ec1f
Source dataset
uspto-grants-2013_04
Patent number
US08420647B2

Reaction notes

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