Thionyl Chloride → 2-Chloronicotinic acid
Reaction equation
Br[C:2]1[CH:3]=[N:4][C:5](O)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(Cl)([Cl:14])=O>>[Cl:14][C:5]1[N:4]=[CH:3][CH:2]=[CH:10][C:6]=1[C:7]([OH:9])=[O:8]Participants
Procedure
Substituted pyridines 12 can be prepared by the procedure described in Scheme 4. A solution of sodium hypobromite is freshly prepared and added to a 2-hydroxynicotinic acid 7 and heated, such as at a temperature of about 50° C. Additional sodium hypobromide may be added to form the bromo compound 8 as needed. The 5-bromo-2-hydroxynicotinic acid 8 is reacted with thionyl chloride, at suitable temperature, such as at a temperature >RT, and preferably at about 80° C., to form the 2-chloro-nicotinic acid analog 9. The acid is coupled with an amine, preferably in the presence of a suitable coupling agent(s), such as EDC, HOBT, and DIEA, to form the corresponding substituted amide 10. Suzuki coupling with the bromo nicotinamide 10 and suitable boronic acids, provides the substituted nicotinamide 11. 2-Amino-nicotinamides 12 are prepared from the corresponding chloro compounds 11 such as by reacting with substituted amines at a suitable temperature, such as about 80° C.
Sources & evidence
- ORD record
- ord-e3f93ad66dc84c42b016b81a12837149
- Source dataset
- uspto-grants-2009_03
- Patent number
- US07507748B2
Reaction notes
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