1-Hydroxybenzotriazole → 3-Amino-5-methyl-pyrazin-2-carboxylic acid methoxy-methyl-amide
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
Reactant 5
Product 1
Reagents, catalysts & solvents 1
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
- concentrationThe solvent is concentrated in vacuo
- additionthe residue is diluted with EtOAc and aq. NaHCO3
- customThe phases are separated
- washthe aqueous layer washed with EtOAc
- washwashed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated in vacuo
- customPurification by flash chromatography (SiO2, 0-5% MeOH in DCM)
Sources & evidence
- ORD record
- ord-044f8219342245bb91489cac3c9b8cd8
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08268834B2
Reaction notes
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