p-Toluenesulfonic acid → 5-bromo-4-chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidine
Reaction equation
[Br:1][C:2]1[C:3]([Cl:10])=[N:4][C:5]([NH2:9])=[N:6][C:7]=1[CH3:8].[CH3:11][C:12](=O)[CH2:13][CH2:14][C:15](=O)[CH3:16].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:3]([Cl:10])=[N:4][C:5]([N:9]2[C:15]([CH3:16])=[CH:14][CH:13]=[C:12]2[CH3:11])=[N:6][C:7]=1[CH3:8]Participants
Procedure
A flask containing a mixture of 5-bromo-4-chloro-6-methylpyrimidin-2-amine (34.8 mmol), 2,5-hexanedione (6.15 mL, 52.2 mmol), and p-toluenesulfonic acid (330 mg, 1.74 mmol) in toluene (100 mL) was fitted with a Dean-stark apparatus and condenser and the mixture was heated to reflux. After refluxing overnight the solution was cooled to room temperature and concentrated. The residue was slurried in hexanes, filtered and the filtrate was concentrated. The precipitate was purified by flash chromatography eluting with hexanes/chloroform (0-50%) to afford the 5-bromo-4-chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidine (1.60 g, 15%). The concentrated filtrate was purified by flash chromatography eluting with hexanes/chloroform (10-40%) to afford 5-bromo-4-chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-methylpyrimidine (5.22 g, 50%).
Workup
- additionA flask containing
- customwas fitted with a Dean-stark apparatus and condenser
- temperaturethe mixture was heated to reflux
- temperatureAfter refluxing overnight the solution
- concentrationconcentrated
- filtrationfiltered
- concentrationthe filtrate was concentrated
- customThe precipitate was purified by flash chromatography
- washeluting with hexanes/chloroform (0-50%)
Sources & evidence
- ORD record
- ord-20eb96483ed043329aad3fb3ae6093f7
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08273755B2
Reaction notes
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