N,N-Dimethylaniline → HCID 89437205, compound

HRID 593205Notes

Reaction equation

HRID 593205 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][C:5]([Br:8])=[CH:4][N:3]=1.CN(C)C1C=CC=CC=1.[CH3:18][O:19][C:20](=[O:26])[CH2:21][CH2:22][C:23](Cl)=[O:24]>O1CCCC1>[Br:8][C:5]1[N:6]=[CH:7][C:2]([NH:1][C:23](=[O:24])[CH2:22][CH2:21][C:20]([O:19][CH3:18])=[O:26])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 5995392-Amino-5-bromopyrazine

Product 1

HCID 89437205HCID 89437205, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 2-amino-5-bromopyrazine (commercially available, 0.687 g, 1.0 eq.) was dissolved in tetrahydrofuran (10 mL). Then N,N-dimethylaniline (500 μL, 1.0 eq.) and methyl-4-chloro-4-oxo-butanoate (535 μL, 1.1 eq.) was successively added. The mixture was refluxed for 12 h. The reaction was stopped and the solution was partitioned between ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate (2×). The combined organic layer were dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography eluting with cyclohexane-ethyl acetate to give methyl 4-[(5-bromopyrazin-2-yl)amino]-4-oxo-butanoate A2 (70%). 1H NMR (400 MHz, DMSO-d6) δ 11.02 (bs, 1H), 9.12 (s, 1H), 8.62 (s, 1H), 3.60 (s, 3H), 2.74 (t, 2H), 2.62 (t, 2H) ppm. LC-MS (Method A): RT 1.28, 290 (M+H+)

Workup

  1. temperatureThe mixture was refluxed for 12 h
  2. customthe solution was partitioned between ethyl acetate and water
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×)
  5. customThe combined organic layer were dried on magnesium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by flash chromatography
  8. washeluting with cyclohexane-ethyl acetate

Sources & evidence

ORD record
ord-ffa902d8bbfa497fa4b0397b38695202
Source dataset
uspto-grants-2016_01
Patent number
US09241489B2

Reaction notes

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