Bromine → 9-bromo-4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-1,4-a,7-triaza-benzocycloheptene-7-carboxylic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][C:10]2=[N:13][C:14]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][N:19]=3)=[CH:15][C:16](=[O:17])[N:9]2[CH2:8][CH2:7]1)=[O:5])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:34]Br>O1CCCC1>[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH:11]([Br:34])[C:10]2=[N:13][C:14]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][N:19]=3)=[CH:15][C:16](=[O:17])[N:9]2[CH2:8][CH2:7]1)=[O:5])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -30 °C
Procedure
To a solution of 4.5 g (14.27 mmol) of 4-oxo-2-pyrimidin-4-yl-5,6,8,9-tetrahydro-4H-1,4a,7-triaza-benzocycloheptene-7-carboxylic acid ethyl ester in dry tetrahydrofuran (140 mL) under argon at −30° C. was added 15.70 mL (15.70 mmol) of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran). The solution was stirred at −30° C. for 5 min and 0.77 mL (14.98 mmol) of bromine was added. The reaction was stirred at −30° C. to room temperature during 3 hours. The mixture was quenched with the addition of a saturated solution of ammonium chloride and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (dichloromethane with 1 to 3% of methanol) to afford 2.6 g (46%) of product.
Workup
- stirringThe reaction was stirred at −30° C. to room temperature during 3 hours
- customThe mixture was quenched with the addition of a saturated solution of ammonium chloride
- extractionextracted with ethyl acetate
- dry with materialThe organic phase was dried over sodium sulfate
- concentrationconcentrated
- customThe residue was purified by flash chromatography (dichloromethane with 1 to 3% of methanol)
Sources & evidence
- ORD record
- ord-4fb80ace0e1440c08109ac2b91b1ba8f
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08507476B2
Reaction notes
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