Pyrazinecarboxylic esters

To synthesize pyrazinecarboxylic esters and pyrazinecarboxamides, chloropyrazines were subjected to Pd-catalyzed carbonylation reactions in either alcohols or dialkylamines [44, 45]. 2-Chloro-3,6-dimethylpyrazine (23) was smoothly carbonylated in methanol containing a catalytic amount of Pd(dba)2 and Ph3P to give 2-methoxycarbonyl-3,6-dimethylpyrazine (70). Somewhat lower yields were observed in the preparation of pyrazinecarboxylic diesters under the same conditions. 

The carbonylation was extended to 2-chloro-3,6-dimethylpyrazine too (7.61.). Under the same conditions as in 7.60. this compound led to the formation of the pyrazinecarboxylic ester in high yield.80... 

This section covers the preparation and reactions of nuclear or extranuclear pyrazinecarboxylic esters, pyrazinecarboximidates, and the like. Pyrazinecarboxylic esters exhibit antimycobacterial activities akin to those of pyrazinecarboxamides 651 the structure-activity relationship of such esters has been studied.656... 

Several reactions of pyrazinecarboxylic esters have been discussed already reduction to N-alkylpiperazines (Section 3.2.2.2), reduction to extranuclear hydrox-ypyrazines (Section 5.2.1), and hydrolysis to pyrazinecarboxylic acids (Section 8.1.1). Other reactions to be expected of carboxylic or carboximidic esters are typified in the following classified examples ... 

Note Reactions of the mixed-Claisen type afford a convenient route from pyrazinecarboxylic esters to some pyrazine ketones. 

Several routes to such derivatives have been covered already by primary synthesis (Chapters 1 and 2), from halogenopyrazines by displacement (Section 4.2.9), from pyrazine carboxylic acids (Section 8.1.2), from pyrazinecarboxylic esters (Section 8.2.2), and from pyrazinecarbonyl halides (Section 8.3.2). The remaining methods of preparation are illustrated in the following examples ... 

Most of the usual routes to such aldehydes have been covered already by primary synthesis in Chapters 1 and 2, by oxidation of alkylpyrazines in Section 3.2.4.1, by oxidation of hydroxymethylpyrazines, in Section 5.2.2, and by reduction of pyrazinecarboxylic esters in Section 8.2.2. 

Many carbamoylpyrazines and related compounds such as IV-hydroxyamides (hydroxamic acids), hydrazides, cyanamides, guanidinocarbonyl-, guanidino-carbamoyl-, and ureidocarbonylpyrazines have been prepared from pyrazinecarboxylic esters. The amides were usually prepared with ammonia in methanol (or other alcohols) but also under other conditions. 

To synthesize pyrazinecarboxylic esters and pyrazinecarboxamides, chloropyrazines were... 

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