2.6- Diamino-3-chloro-5- pyrazine

Carbamic carboxylic anhydrides, such as 3,5-diamino-6-chloro-pyrazine-carboxylic N,N-diphenylcarbamic anhydride, and their viny-... 

N-Amidinopyrazine carboxamides. The synthesis and biological activity of a great number of compounds of this type were described in a series of papers between 1965 and 1 68 [159—162]. The first of these described the diuretic activity in adrenalectomised DOC A-treated rats of a series of A -amidino-3-amino-6-halopyrazine carboxamides. In the second paper, it was discovered that the introduction of a 5-amino group into the pyrazine ring increased the diuretic potency. One of the compounds, amiloride (A -amidino-3,5-diamino-6-chloro-pyrazine carboxamide (Figure 1.13)) later became widely used in clinical practice, particularly in combination with other diuretics. Its use in combination with diuretics acting more proximally in the nephron is related to the prevention of potassium loss which results when an excess sodium load is delivered to the distal tubule. Thus, amiloride is a potassium-sparing diuretic [163]. 

Heating of 3,4-diamino-l,2,5-oxadiazole 156 and the relatively common 2-chloro-l,5-diketone gave 1,2,5-oxadi-azolo[3,4- ]pyrrolo[l,2- ]pyrazine 164 (Equation 27) <1999CHE882>. 

Pyrazine and pyrimidine heterocycles, like pyridine, are electron deficient and need the presence of an activating/electron-releasing group to allow efficient electrophilic nitration to occur. An example of this strategy is seen during the synthesis of 2,6-diamino-3,5-dinitropyrazine (ANPz) (183) where one of the chloro groups of 2,6-dichloropyrazine (180) is substituted for a... 

Trichloropyrazine gave 2-chloro-5,6-bis(4,6-diaminopyrimidin-5-ylthio)-pyrazine (153) [4,6-diamino-5-pyrimidinethiol, KOH, AcNMe2—H20, reflux, 4 h 93% (based on the pyrimidinethiol )].1312 Also other examples,1602 including use of K-Selectride + alkanethiol.1738... 

Dimethylbut-l-enyl)-6-methylpyrazine 2-(2,3-Dimethylbutyryl)pyrazine Dimethyl 5-chloro-6-methoxy-2,3-pyrazinedicarboxylate Dimethyl 5,6-diamino-2,3-pyrazinedicarboxylate Dimethyl 5,6-dichloro-2,3-pyrazinedicarboxylate... 

Reduction of 2,6-diamino-3,5-dinitropyrazine in dimethylacetamide with hydrogen over platinum oxide (or with sodium sulfide and ammonium chloride in water at room temperature) gave 2,3,5-triamino-6-nitropyrazine (1180), but reduction with hydrogen and 10% palladium on charcoal at 50p.sJ. gave tetraamino-pyrazine (1180). 2-Amino-5hydrochloric acid at reflux gave 2-chloro-5-(3, 3 -dimethylureido)-... 

Amino-3-methoxycarbonylpyrazine with urea in the presence of sodium hydride in dimethylformamide at — 15° gave 2-amino-3-ureidocarbonylpyrazine (1152, 1322). The reaction was also applied to the following pyrazines 2-amino-5-chloro-3-methoxy carbonyl (1152) 2,6-diamino-3-chloro-5-methoxycarbonyl (1380) 2-amino-5-chloro-3-methoxycarbonyl-6-methylamino (1380) 2-amino-5-chloro-6-dimethylamino(and other dialkylamino)-3-methoxycarbonyl (1152) and 2-amino-5-chloro-3-methoxycarbonyl-6-methylthio (1152). The preparation of ureidocarbonylpyrazines from A -cyanamides has been described in Section 2C(2)(d). 

Diamino-3-chloro-5-hydrazinocarbonylpyrazine with nitrous acid at 50-55° formed 2,6-diamino-3-azidocarbonyl-5-chloropyrazine, which, refluxed with a solution of guanidine hydrochloride and sodium isopropoxide in propan-2-ol, gave 2,6-diamino-3-chloro-5-guanidinocarbonylpyrazine and many similar preparations were reported (1371). 2-Amino-5-chloro-3-hydrazinocarbonylpyrazine treated with nitrous acid gave 2-amino-3-azidocarbonyl-5-chloropyrazine, which was pyrolyzed to 5-chloro-2-hydroxyimidazo(4,5-Z)]pyrazine (1226). 

Iminoethers were also prepared from 2-amino-3-cyanopyrazine with ethanolic hydrogen chloride (792, 1218) [the product with guanidine and sodium methoxide in methanol formed 2-amino-3-(C-guanidino-C-iminomethyl)pyrazine (878, 1218)] from 2,6-diamino-3-chloro-5-cyanopyrazine with ethanolic hydrogen chloride at 0 (the product heated with ethanol gave 2,6-diamino-3-chloro-5-triethoxymethyl-pyrazine) (1432) from 2-amino-5-chloro-3-cyanopyrazine the product with... 

A -(2 -imidazolin-2 -yl)amidino]pyrazine (59) (877)) and from 2,6-diamino-3-chloro-5-cyanopyrazine [the product heated with dimethylamine in ethanol at 40° gave 2,6-diamino-3-chloro-5-(A(,A -dimethylamidino)pyrazine] (1361). 2-Chloro-... 

---