1-Hydroxybenzotriazole → 3-Amino-5-methyl-pyrazin-2-carboxylic acid methoxy-methyl-amide

HRID 81491Notes

Reaction equation

HRID 81491 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([OH:11])=O)=[N:4][CH:5]=[C:6]([CH3:8])[N:7]=1.C([N:15]([CH:18](C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:44][O:45]NOOC>CN(C=O)C>[CH3:44][O:45][N:15]([CH3:18])[C:9]([C:3]1[C:2]([NH2:1])=[N:7][C:6]([CH3:8])=[CH:5][N:4]=1)=[O:11]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2792333-Amino-5-methylpyrazine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22015712N,O-dimethoxyhydroxylamine hydrochloride

Product 1

HCID 866697723-Amino-5-methyl-pyrazin-2-carboxylic acid methoxy-methyl-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

3-Amino-5-methyl-pyrazin-2-carboxylic acid (0.48 g, 3.12 mmol) is dissolved in anhydrous DMF (10 ml) under N2. The brown solution is cooled to 0° C., and diisopropylethylamine (1.48 ml, 7.9 mmol), EDC.HCl (0.75 g, 3.8 mmol), HOBt (0.58 g, 3.8 mmol) and N,O-dimethoxyhydroxylamine hydrochloride (0.37 g, 3.8 mmol) are added and the reaction is stirred at 0° C. for 1 hour and at room temperature for 4 hours. The solvent is concentrated in vacuo, and the residue is diluted with EtOAc and aq. NaHCO3. The phases are separated and the aqueous layer washed with EtOAc. The organic layers are combined, washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by flash chromatography (SiO2, 0-5% MeOH in DCM) yields 3-amino-5-methyl-pyrazin-2-carboylic acid methoxy-methyl-amide as a pale yellow solid. [M+H]+ 197.

Workup

  1. concentrationThe solvent is concentrated in vacuo
  2. additionthe residue is diluted with EtOAc and aq. NaHCO3
  3. customThe phases are separated
  4. washthe aqueous layer washed with EtOAc
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography (SiO2, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-f78b54efc47940d9b0ae99b22287dd82
Source dataset
uspto-grants-2014_09
Patent number
US08846687B2

Reaction notes

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