Pyridine 2-methoxy-3-chloro

The order NO2 > Cl, which is known for the reactions of nitro-activated aromatic compounds, is also found for pyridine and quinoline derivatives. In the reaction of 2-chloro-4-nitroquinoline with methoxide ion, only the 4-methoxide derivative is formed, as shown by gas-chromatography, whereas 2,4-dichloroquinoline yields a mixture of the isomeric chloro-methoxy derivatives in comparable amounts. ... 

When the 4-position is substituted, Grignard addition occurs at the 2-position, to eventually give a 2,4,6-trisubstituted pyridine via the 6-lithiated species (Scheme 145) (88TL1751). Alternatively, if the 4-substituent is a chloro (88TL1751) or methoxy group (89TL5053), the initial product can be hydrolyzed to an enone rather than being aromatized to a pyridine. 

The acylation of a series of pyrazolo[3,4-c]pyridines has been studied.110 Acetic anhydride in refluxing benzene converted S-substituted derivatives to 1-acyl compounds (101 R2 = H), whereas the 7-methoxy derivative afforded the 2-substituted product 102 (R1 = H, R2 = OMe), attributed to peri interaction. In the absence of solvent, however, the latter reaction gave the 1-acyl isomer as the major product. Furthermore, benzoylation of the 5-chloro bicycle furnished a mixture of 101 and 102 (R1 = Cl, R2 = H). However, products benzoylated mainly at N-6 were obtained following introduction of a nitro group into the pyrazole ring. 

The methoxy group in 7-methoxy,2 7-methoxy-6-methyl,41 and 7-methoxy-4-methylisatin41 has been cleaved to the corresponding hydroxy group with pyridine hydrochloride, while treatment with sodium hydroxide cleaves the 6-methoxy group of 5-chloro-6,7-dimethoxy-l-methylisatin.48 5-Acetamidoisatins have been hydrolyzed to 5-aminoisatins.30 Isatin carboxylic acids have been converted to amides and esters by means of standard procedures.52,53... 

Omeprazole is obtained [15] by the reaction of acetyl ethyl propionate 1 with ammonia to give ethyl -3-amino-2,3-dimethyl acrylate 2. Compound 2 was converted to to 2,4-dihydroxy-3,5,6-trimethyl pyridine 3 by treatment with methyl diethylmalonate. Treatment of compound 3 with phosphorous oxychloride produced 2,4-dichloro-3,5/6-trimethyl pyridine 4. 4-Chloro-3/5,6-trimethyl pyridine 5 was obtained by treatment of compound 4 with hydrogen. On treatment of compound 5 with hydrogen peroxide and acetic acid, 4-chloro-3,5,6-trimethyl-pyridine-N-oxide 6 was produced. Treatment of compound 6 with acetic anhydride gave 4-chloro-2-hydroxymethyl-3,5-dimethyl pyridine 7 which was converted to 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine 8 by treatment with sodium methoxide. Compound 8 was treated with thionyl chloride to produce 2-chloromethyl-3,5-dimethyl-4-methoxypyridinc 9. Compound 9 interacts with 5-methoxy-2-mercaptobenzimidazole to give 5-methoxy 2-[((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)thio]-lH-bcnzimidazole 10 which is oxidized to omeprazole 11. 

Methyl-l-penten-3-one-l-ol 1 and glacial acetic acid in benzene was added to pyrrolidine to give 2-methyl-l-pen ten-1-[N-pyrrolidinyl]-3-one 2. Compound 2 when treated with oxalyl chloride and methanol was added, 3,5-dimethyl-2-methoxycarbonyl-4-pyrone 3 was produced. Treatment of compound 3 with sodium borohydride in methanol gives 3,5-dimethyl-2-hydroxymethyl-4-pyrone 4. Compound 4 was converted to 3,5-dimethyl-2-hydroxymethyl-4-pyridone 5 by heating compound 4 with aqueous ammonia in a sealed flask. Compound 5 was converted to 4-chloro-2-chloromethyl-3,5-dimethyl pyridine 6 by treatment with phosphorous oxychloride. Treatment of compound 6 with 5-methoxy-2-mer-captobenzimidazole in tetrahydrofuran gave 2-[2-(4-chloro-3,5-dimethyl pyridinyl)methylthio]-5-methoxy benzimidazole 7. When compound 7 was treated with potassium hydroxide in dimethyl sulfoxide containing methanol, 2-[2-(3,5-dimethyl-4-methoxypyridinyl)methylthio]-5-methoxy... 

All these amination reactions show exclusive SNH substitution. There is hardly any indication for the formation of 3-nitropyridines, in which the chloro or methoxy group was replaced by an amino group, even when these leaving groups are present at the reactive a-position of the pyridine ring. It seems to be a characteristic feature of the oxidative amination... 

Methylation of 6-chloro-4-hydroxy-3-methylisothiazolo[5,4-6]pyridine (200) with ethereal diazomethane for 13 h gave the 4-methoxy derivative (201) (93%) <90JCS(P1)1477>. None of the 7-methyl derivative was observed in the reaction, indicating that compound (200) exists almost exclusively as the 4-hydroxy tautomer and that the tautomeric 6-chloro-3-methylisothiazolo[5,4-6]pyridin-4-one (202) does not contribute significantly to the equilibrium. 

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