1,3,4-Thiadiazole, 2-amino-5-methyl- → 2-(2-Methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetic acid
Reaction equation
[CH3:1][C:2]1[S:6][C:5]([NH2:7])=[N:4][N:3]=1.C([O:10][C:11](=[O:17])[CH2:12][C:13](=O)[CH2:14]Br)C>CO>[CH3:1][C:2]1[S:6][C:5]2=[N:7][C:13]([CH2:12][C:11]([OH:17])=[O:10])=[CH:14][N:4]2[N:3]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
A mixture of 5-methyl-[1,3,4]thiadiazol-2-ylamine (300 mg, 2.6 mmol), 4-bromo-3-oxo-butyric acid ethyl ester (908 mg, 2.6 mmol) and 5 mL of MeOH was combined in a sealed tube and was heated to 80° C. for 3 hours. The reaction was cooled and the MeOH was removed in vacuo. The residue was dissolved in dichloromethane and the organic solution was washed with saturated aqueous NaHCO3 solution (2×). The organic solution was dried over sodium sulfate, filtered and concentrated. The crude product was purified by Combiflash (Teledyne ISCO, Lincoln, Nebr.) chromatography using 0-100% EtOAc/heptanes. Both the desired product and (2-methyl-imidazo[2,1-b][1,3,4]thiadiazol-6-ylyacetic acid methyl ester (formed by trans esterification with solvent MeOH) were obtained with a total mass of 333 mg (54%). The crude mixture was used directly in the next step
Workup
- customwas combined in a sealed tube
- temperatureThe reaction was cooled
- customthe MeOH was removed in vacuo
- dissolutionThe residue was dissolved in dichloromethane
- washthe organic solution was washed with saturated aqueous NaHCO3 solution (2×)
- dry with materialThe organic solution was dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by Combiflash (Teledyne ISCO, Lincoln, Nebr.) chromatography
Sources & evidence
- ORD record
- ord-4a6e6b1b609147f5aaffe93ae728c1a2
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08609680B2
Reaction notes
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