2-Dimethylamino pyrazine

The ultraviolet spectra in aqueous solution (821) of the methiodides isolated from the methylation of 2-amino- and 2-dimethylaminopyrazines with methyl iodide in methanol (821) differed from those obtained by protonation of 2-amino-and 2-dimethylaminopyrazine, respectively. This methiodide of 2-aminopyrazine was rapidly decomposed by aqueous alkali but did not form l-methyl-2-oxo(or imino)-l, 2-dihydropyrazine or 2-methylaminopyrazine (821). These and other observations were consistent with protonation of 2-amino(2-methylamino or 2-dimethylamino)pyrazine at N, and with the methiodides isolated involving quater-nization at N4 (821). It has been claimed from studies of ultraviolet and infrared spectra and from reactions with cyanoguanidine that in 2-aminopyrazine p-toluenesulfonate, the amino group is protonated (1189). 

Tetrabromopyrazine with concentrated ammonium hydroxide at 120° afforded 2,3-diamino-5,6-dibromopyrazine and 2,6-diamino-3,5-dibromopyrazine (684, 970). 2,5-Dichloro-3,6-difluoropyrazine and dimethylamine gave 2,5-dichloro-3-dimethylamino-6-fluoropyrazine, and under more severe conditions 2,5-dichloro-3,6-bis(dimethylamino)pyrazine (888). 2-Bromo-3,5,6-trifluoropyrazine with dimethylamine gave 2-bromo-5-dimethylamino-3,6-difluoropyrazine (885). 

Tetracyanopyrazine has been reported to react with liquid ammonia in tetra-hydrofuran to give 2,6-diamino-3,5-dicyanopyrazine (1180, 1182), and with dimethylamine in tetrahydrofuran at 0° to give 2,3,5-tricyano-6-dimethylamino-pyrazine (97.7%) (158), and this on treatment with ammonia in tetrahydrofuran gave 2-amino-3,5-dicyano-6-dimethylaminopyrazine (89%) (158). 

Amino-pyrazines and -pyridazines have been shown to exist predominantly in the amino form by infrared spectroscopic studies (cf. Table VI). Ultraviolet spectral data have been interpreted to indicate that 4-aminocinnoline exists predominantly in the imino form 256, but this conclusion, which was based on comparison of its spectrum with those of cinnolin-4-one and 4-ethoxycinnoline, is probably incorrect. Ultraviolet spectroscopic data strongly support the predominance of amino structures for 2-aminopyrazine (257) and 2-aminoquin-oxaline how ever, the former compound was at first erroneously concluded to exist in the imino form from ultraviolet spectral evidence. Isolation of two isomers of 2-amino-8-dimethylamino-3-methylphenazine, assigned the amino and imino structures 258 and 259, respectively, has been claimed, but it is very unlikely that these assignments are correct. 

A research team at Rhone-Poulenc reported a four-component procedure for the synthesis of variously substituted heteroaromatic tetrazolo[l,5-zz]pyrazines <1998TL2735>. Thus, aldehydes, primary amines, trimethylsilyl azide, and methyl /3-(iV,iV-dimethylamino)-a-isocyanoacrylates 117 were reacted in a methanolic solution at room temperature to yield the product 119 in high yields. The reaction was rationalized to proceed via the formation of intermediate 118. The procedure proved to be efficient for combinatorial chemical applications. 

Interaction of substituted dienediamines with ethylenediamine yields im-idazo[3,2-n]pyridine derivatives (95JHC477). 3-Arylaminoindoles, with distinct enamine properties, are the starting materials for the synthesis of indolo[3,2-b]quinoline derivatives [96KFZ(7)42]. a-Carboline derivatives can be obtained from enamine-based 3-dimethylamino-2-indolinones [96KFZ(9)35, 96KFZ(10)32], The synthesis and transformation of enamines based on the pyrido[l,2-n]pyrazine ring system into imidazo[l,2-n]pyridine and imidazo[l,2-a]pyrimidine derivatives have been reported... 

Cptd Ck hn n cooh O 2-Pyrazine carboxylic acid Sj COOH 4-(Dimethylamino)phenylacetic acid v /= COOH >-o ... 

Reaction of methyl 2-( 1 -methoxycarbonyl-4-oxo-4//-pyrido[ 1,2-a]-pyrazin-3-yl)acetate (144) with ferf-butoxybis(dimethylamino)methane furnished 3-dimethylaminoacrylate 145 (96JHC639). Urea 146 was obtained from 145 with cyanamide. 

Amino-5-dimethylamino-2-pyrazinecarboxylic acid 3-Amino-6-dimethylamino-2-pyrazinecarboxylic acid 3-Amino-5-dimethylamino-2,6-pyrazinedicarbonitrile 5-Amino-6-dimethylamino-2,3-pyrazinedicarboxamide 3- Amino-6-(3,3-dimethylbut-1 -ynyl)-2-pyrazinecarbonitrile 3-Amino-/V, /V -dimethyl-2-pyrazine-carbohydrazide... 

Prnpan 2-Dimethylamino-2-(4-nitro-phenyl)- El9a, 499 (Cl -> NR2) Pyrazin-l-oxid, 3,5(or3,6)-Diisopro-pyl-2-formyl- E9b/2, 322 (H -> CHO)... 

Pyrido[3,2-b pyrazin 7-Carboxy-3-dimethylamino-5-ethyl-8-oxo-5,8-dihydro- E9c, 248 (SR NR2)... 

Chlorination of 2-methylpyrazine in acetic acid at 100° gave 2-trichloromethyl-pyrazine (685, 686), whereas 2-chloro-3-methylpyrazine under similar conditions gave 2-chloro-3-dichloromethylpyrazine (685, 687, 688). Chlorine bubbled into a stirred solution of 3-dimethylamino-2,5-dimethylpyrazine in chloroform gave the 6[Pg.80]

Dichloro-3,6dipropyl(or 3,6-diisopropyl or 3,6diisobutyl)pyrazine heated with hexamethylphosphoramide at 200° for 2-3 hours gave 81% 2-chloro-5-dimethylamino-3,6-dipropyl(or 3,6diisopropyl or 3,6-diisobutyl)pyrazine (937), but 2,6-dichloro-3,5diphenylpyrazine heated with hexamethylphosphoramide at 200° for 3 hours gave 64% 2,6-bisdimethylamino-3,5-diphenylpyrazine (937). 

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