4-Bromo-3-(4-fluoro-phenyl)-7-hydroxy-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester → 4-Cyano-3-(4-fluoro-phenyl)-7-hydroxy-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester
Reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9](Br)[C:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[CH:13][S:14][C:7]=2[C:6]=1[OH:22])=[O:4].[Cu][C:24]#[N:25]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9]([C:24]#[N:25])[C:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[CH:13][S:14][C:7]=2[C:6]=1[OH:22])=[O:4]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 150 °C
Procedure
A mixture of 4-bromo-3-(4-fluoro-phenyl)-7-hydroxy-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester (58.5 mg, 0.153 mmol), example 32-a, and copper(I) cyanide (27.4 mg, 0.306 mmol) suspended in 1.5 mL of DMF was heated at 150° C. for 30 minutes. The resultant mixture was partitioned between ethyl acetate and water, and the organic fraction was washed with brine, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-20% methanol in methylene chloride to produce 15.1 mg of a white solid. MS: (+) m/z 329.0 (M+1).
Workup
- customThe resultant mixture was partitioned between ethyl acetate and water
- washthe organic fraction was washed with brine
- dry with materialdried over anhydrous sodium sulfate
- concentrationconcentrated
- customThe crude product was purified by flash chromatography
- washeluting from silica gel with a gradient of 0-20% methanol in methylene chloride
Sources & evidence
- ORD record
- ord-f859f667f078464ebba9e7327f5e456c
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08703795B2
Reaction notes
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