2-Chloro-4-methyl-5-nitropyridine → 2-Chloro-5-nitropyridine-4-carbaldehyde
Reaction equation
[OH:1]C1C2C(=CN=C(Cl)C=2)N=CC=1.[Cl:13][C:14]1[CH:19]=[C:18]([CH3:20])[C:17]([N+:21]([O-:23])=[O:22])=[CH:16][N:15]=1>>[Cl:13][C:14]1[CH:19]=[C:18]([C:17]([N+:21]([O-:23])=[O:22])=[CH:16][N:15]=1)[CH:20]=[O:1]Participants
Procedure
A route to prepare 4-hydroxy 6-chloro 1,7 napthyridine is depicted in Scheme III. Starting with 2-chloro-4-methyl-5-nitropyridine, condensation with dimethylformamidedimethylacetal and subsequent oxidative cleavage yields 2-chloro-5-nitroisonicotinaldehyde. Chemoselective methyl addition to the aldehyde with methyllithium and titaniumtetrachloride at −50° C. followed by oxidation yields 1-(2-chloro-5-nitropyridin-4-yl)ethanone. Nitro reduction with iron in acetic acid, followed by a two step monotosylation yields N-(4-acetyl-6-chloropyridin-3-yl)-4-nitrobenzenesulfonamide. Upon heating with dimethylformamidedimethylacetal and diisopropylethylamine in DMF at 105° C. and subsequent treatment with thiophenol at room temperature, 6-chloro-1,7-naphthyridin-4-ol is obtained IV. Conversion of IV to the corresponding triflate or benzyl ether using standard conditions yields bifunctional intermediates which can be taken through the chemical transformation depicted in Schemes 1 and 2 to yield 4,6 disubstituted 1,7 naphthyridines V.
Sources & evidence
- ORD record
- ord-1d19cf9444db4925a69c663bc7bbb495
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735424B2
Reaction notes
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