Dimethylformamide → 3,4-dihydro-2,2-dimethyl-4-(2-methoxy-3-pyrazinyl)carbonyl-6-nitro-2H-1,4-benzoxazine

HRID 37114Notes

Reaction equation

HRID 37114 reaction equation
[CH3:1][C:2]1([CH3:15])[CH2:7][NH:6][C:5]2[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=[CH:11][C:4]=2[O:3]1.[H-].[Na+].Cl[C:19]1[C:24]([C:25]([O:27]C)=O)=[N:23][CH:22]=[CH:21][N:20]=1.CN(C)[CH:31]=[O:32]>>[CH3:1][C:2]1([CH3:15])[CH2:7][N:6]([C:25]([C:24]2[C:19]([O:32][CH3:31])=[N:20][CH:21]=[CH:22][N:23]=2)=[O:27])[C:5]2[CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=[CH:11][C:4]=2[O:3]1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 1519497Methyl 3-chloropyrazine-2-carboxylateHCID 107270572,2-Dimethyl-6-nitro-3,4-dihydro-2H-benzo[B][1,4]oxazine

Product 1

HCID 152917763,4-dihydro-2,2-dimethyl-4-(2-methoxy-3-pyrazinyl)carbonyl-6-nitro-2H-1,4-benzoxazine

Procedure

In 40 ml of N,N-dimethylformamide was dissolved 3.33 g of 3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazine followed by addition of 0.77 g of sodium hydride. The mixture was stirred at room temperature for 30 minutes and ice-cooled. Then, 6 ml of a solution of 2.76 g of methyl 2-chloropyrazine-3-carboxylate in N,N-dimethylformamide was added dropwise at a temperature not exceeding 5° C. The reaction mixture was then stirred at room temperature for 3.5 hours, at the end of which time it was poured in ice-water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure and the residue was purified by silica gel column chromatography. The resulting crude crystals were recrystallized from ethanol to give 1.27 g of 3,4-dihydro-2,2-dimethyl-4-(2-methoxy-3-pyrazinyl)carbonyl-6-nitro-2H-1,4-benzoxazine. This compound was found to have the following physicochemical properties.

Workup

  1. temperatureice-cooled
  2. customexceeding 5° C
  3. stirringThe reaction mixture was then stirred at room temperature for 3.5 hours, at the end of which time it
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationThe solvent was then distilled off under reduced pressure
  8. customthe residue was purified by silica gel column chromatography
  9. customThe resulting crude crystals were recrystallized from ethanol

Sources & evidence

ORD record
ord-3627bc27fd834ac3b94f84a9bae14186
Source dataset
uspto-grants-1995_05
Patent number
US05420126

Reaction notes

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