Trimethyl orthoformate → N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-2,2-dimethyl-propionamide

HRID 719926Notes

Reaction equation

HRID 719926 reaction equation
[C:1]([C:4]1[N:5]=[CH:6][C:7]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[N:8][CH:9]=1)(=[O:3])[CH3:2].O.[C:18]1(C)C=CC(S(O)(=O)=O)=CC=1.[CH:29](OC)(OC)[O:30]C>CO>[CH3:18][O:3][C:1]([C:4]1[N:5]=[CH:6][C:7]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[N:8][CH:9]=1)([O:30][CH3:29])[CH3:2]

Participants

5

Reactant 3

HCID 9005Trimethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 21897264N-(5-acetylpyrazin-2-yl)-2,2-dimethylpropanamide

Product 1

HCID 21897278N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-2,2-dimethyl-propionamideYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of N-(5-acetyl-pyrazin-2-yl)-2,2-dimethyl-propionamide (prepared as in Example 28, 2.00 g, 9.038 mmol) in trimethyl orthoformate (13.5 mL) and methanol (36 mL) was treated with p-toluenesulfonic acid monohydrate (174.5 mg, 0.904 mmol). The resulting reaction mixture was heated under reflux for 2.5 h and then concentrated in vacuo. The residue was diluted with ethyl acetate (200 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (100 mL) and a saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/4 ethyl acetate/hexanes) afforded N-[5-(1,1-dimethoxy-ethyl)-pyrazin-2-yl]-2,2-dimethyl-propionamide as a white solid (1.74 g, 72%): mp 108–109° C.; EI-HRMS m/e calcd for C13H21N3O3 (M+) 267.1583, found 267.1486.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureunder reflux for 2.5 h
  4. concentrationconcentrated in vacuo
  5. additionThe residue was diluted with ethyl acetate (200 mL)
  6. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (100 mL)
  7. dry with materiala saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a3483595a40c40acb5bd828dbfdbf871
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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