2-Carboxy-6-chloropyrazine

Normal nucleophilic substitution occurred on treatment of 2-carbamoyl-3-chloropyrazine with alcoholic methylamine at 130° (423, 836) 2-chloro-3-(4 -morpholinocarbonyOpyrazine with morpholine at reflux in benzene (867) 2dimethyl sulfoxide at 65° (857) and cyclohexylamine in benzene at reflux (946) 3-chloro-2-methoxycarbonyl-5-phenylpyrazine with alcoholic methylamine at 140° (375) 2-carboxy-3-chloropyrazine with anhydrous ammonia at 100° for 5 hours (947) 2-carbamoyl-6-chloropyrazine with aqueous methylamine at reflux (940) 2-chloro-6-(4 -morpholinocarbonyl)pyrazine (and other amides) and 2-chloro-6-methoxycarbonylpyrazine with morpholine (and other amines) (870, 948, 949) and 2-chloro-6-methoxycarbonylpyrazine with liquid ammonia at 80° (870). 2-Chloro-3-methoxycarbonylpyrazine fused with guanidine carbonate gave 2-amino4-hydroxypteridine and its 7-methyl-, 7-phenyl, and 6,7-diphenyl analogues were prepared similarly (371,375). 

Alkylpyrazines with other substituents have been oxidized to carboxylic acids as follows 2-acetamido-6-methylpyrazine was oxidized in aqueous magnesium sulfate with potassium permanganate to 2-acetamido-6aqueous potassium permanganate at room temperature to 2-carboxy-3-chloropyrazine, which was also obtained by oxidation of 2-chloro-3-methylpyrazine with selenium dioxide in boiling aqueous pyridine (947). Oxidations of 2-methoxy-3-methyl-... 

Many derivatives of carboxy chloropyrazines have been prepared by the action of phosphoryl chloride on the corresponding hydroxypyrazine. In this way were prepared 2-chloro-3-methoxycarbonylpyrazine (371, 423, 836), 2-chloro-3-methoxycarbonyl-5,6-diphenylpyrazine (but the corresponding hydroxy compound did not react with phosphorus tribromide) (837), and 3-chloro-2-methoxycarbonyl-... 

Attempted preparations of the acid chloride from 2,6-diamino-3-carboxy-5-chloropyrazine under a variety of conditions were unsuccessful (1331) and in that respect it resembled anthranilic acid. 

Diamino-3-carboxy-5-chloropyrazine A, 7V-diphenylcarbamic anhydride (19), an active ester, has been prepared by addition of diphenylcarbamoyl chloride to 2,6-diamino-3-carboxy-5-chloropyrazine and triethylamine in dimethylformamide, (and other similar compounds were also prepared) (1330, 1344, 1345). This compound was better prepared from 2,6-diamino-3-carboxy-5-chloropyrazine and... 

Diamino-3-carboxy-5-chloropyrazine in dimethyl sulfoxide (a) with N,N dicyclohexylcarbodiimide gave 2,6-diamino-3-chloro-5-(2, 5 -dioxopyrrolidin-l ylcarbonyOpyrazine ( ) (962), (6) with dicyclohexylcarbodiimide (and 2-hydrazino pyrimidine) gave 2,6-diamino-3-chloro-5-(A -cyclohexyl-V-cyclohexylcarbamoyl) carbamoylpyrazine (1331), and (c) as its triethylamine salt with V-ethyl-5-phenyl... 

A comparison has been made of the reactivity of active esters (12,19,29,30) of 2,6-diamino-3-carboxy-5-chloropyrazine in reactions with various amines to give amides (1345). Compound (19) was the most reactive followed by (12) and both more reactive than the others (1345). Compound (12) with sulfurylamide in acetonitrile with triethylamine gave 2,6-diamino-3-aminosulfonylcarbamoyl-5-chloropyrazine (463). 

Dimethoxycarbonylpyrazine heated with hydrazine hydrate in ethanol gave some 5,8-dihydroxypyrazino[2,3-with hydrazines (and amines) has been described in Section 2C(2)(a) (961,1330, 1331). An analogous active ester was prepared from 2-amino-3-carboxy-5-chloro-6-methoxypyrazine and with hydrazine in tetrahydrofuran gave 2-amino-5-chloro-... 

Carboxypyrazine 1-oxide heated with phosphoryl chloride at 40-50° for 15 minutes gave 2-carboxy-6-chloropyrazine (868-870), but Novacek et al. (839) claim that 3-carboxypyrazine 1-oxide refluxed with thionyl chloride for 5.5 hours, and the product treated with ammonia, gave 2-carbamoyl-5-chloropyrazine ( ). 

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