2-Methoxycarbonyl-6- pyrazine

Bei der Reduktion von 2-ChlorcarbonyI-pyrazin werden neben 20°/0 d.Th. 2-Formyl-pyrazin bereits 55% d.Th. 2-[Pyrazyl-(2)-methoxycarbonyl -pyrazin gebildet1 ... 

Amino-3-(methoxycarbonyl)pyrazine 89 is a versatile reagent for the cyclocondensation reactions leading to heterocondensed pteridines 90-93 (Scheme 6) <2001JHC1173>. 

Chlorination of 2-amino-3-methoxycarbonylpyrazine in aqueous acetic acid at about 40° has been shown to give 5-chloro-2-chloroamino-3-methoxycarbonyl-pyrazine and thence 2-amino-5-chloro-3-methoxycarbonylpyrazine (150, 378a, 432a, 778-787), but in the presence of polar aprotic solvents (such as acetonitrile and dichloroethane) at temperatures between room temperature and reflux it gave 2-amino-5,6 -dichloro-3 -me thoxycarbonyIpyrazine (788). 

Amino-3-hydroxypyrazine with phosphoryl bromide at 140-150° for 20 minutes gave 2-amino-3-bromopyrazine (807) and 2-hydroxy-6-methoxycarbonyl-pyrazine with phosphoryl bromide at 125° for 10 minutes gave 2-bromo-6-methoxycarbonylpyrazine (867). 

Hydrolysis of 2,6-diacetoxy-3,5-diphenylpyrazine (9) (from 2-hydroxy-3,5-diphenylpyrazine 1 -oxide by refluxing with acetic acid-acetic anhydride) with potassium hydrogen carbonate in methanol gave 2,6-dihydroxy-3,5-diphenylpyrazine (873), and 2-acetoxy-6-methoxycarbonylpyrazine (from 3-methoxycarbonyl-pyrazine 1-oxide with acetic anhydride) with methanolic hydrogen chloride gave 2-hydroxy-6 -methoxycarbonylpyrazine (838). 

Alkoxycarbonylpyrazines have been oxidized to alkoxycarbonylpyrazine Af-oxides as follows 2-ethoxycarbonylpyrazine with perhydrol gave 3-ethoxy-carbonylpyrazine 1-oxide (575) 2-amino-3-methoxycarbonylpyrazine refluxed with m-chloroperoxybenzoic acid in chloroform gave 2-amino-3-methoxycarbonyl-pyrazine 1-oxide (876,880,1222) the 5-bromo (808, 877,878, 1222) and 5-chloro (875, 876, 879, 1222) derivatives were prepared similarly and some 3-ethoxy-carbonylpyrazine 1-oxides have been prepared by oxidation (reagent not stated) of... 

Carbamoylpyrazine A-oxides are also prepared from the corresponding esters. 3-Methoxycarbonylpyrazine 1-oxide with ammonium hydroxide at reflux gave 3-carbamoylpyrazine 1-oxide (1266) and similarly with hydroxylamine gave 3-N-hydroxy carbamoylpyrazine 1-oxide (1266). 2-Amino-5-chloro-3-methoxycarbonyl-pyrazine 1-oxide with methylamine gave 2-amino-5-chloro-3-A-methylcarbamoyl-pyrazine 1-oxide (876). 

Formyl-pyrazin 36 25 g (0,181 mol) Methoxycarbonyl-pyrazin in 500 ml wasserfreiem THF werden auf —70° unter Stickstoff gekiihlt. Innerhalb von 30 Min. werden bei - 70° 268 ml einer 0,34 m Lithiumalanat-Ldsung in THF (0,091 mol) unter Rlihren zugetropft. 

Pyrazine, 2-amino-5-(3-indoloyl)-synthesis, 3, 180, 181 Pyrazine, 2-amino-3-methoxycarbonyl-chlorination, 3, 163... 

Methyl 2-substituted perhydropyrido[l,2-u]pyrazine-8-acetates were obtained by catalytic hydrogenation of 2-substituted 8-(methoxycarbonyl-methylene)perhydropyrido[l,2-a]pyrazines over 10% Pd/C catalysts (00JAP(K)00/86659). A side chain 4-pyridyl group was hydrogenated over Pt02 catalysts to yield a 4-piperidyl derivative. 

Cyclization of 1 -(9-fluorenylmethoxycarbonyl)-2-[(A-methoxycarbonyl-methyl)aminocarbonyl)piperidine and 2-(9-fluorenylmethoxycarbonyl) -3-[(A-methoxycarbonylmethyl)aminocarbonyl]-1,2,3,4-tetrahydroisoquino-lines on the action of piperidine in THF yielded 2-(l,4-dioxoperhydropyr-ido[ 1,2-fl]pyrazin-2-y 1)- and 2-( 1,4-dioxo-1,3,4,6,11,11 a-hexahydro-2//-pyr-azino[l,2-i]isoquinolin-2-yl)acetamides, respectively (99MIP11). 

Perhydropyrido[l,2- ]pyrazin-l-one was prepared in the reaction of methyl pipecolinate and ethylene imine in boiling EtOH <19951JSP5461047>. Cyclocondensation of ethyl 2-amino-2-(2-pyridyl)acetate with DMAD, followed by treatment of reaction mixture with NaOMe, gave the 2-(l-methoxycarbonyl)-4-oxo-47/-pyrido[l,2- ]pyrazin-3-yl)acetate <1996JHC639>. 

Dimcthoxy-2-isopropyl-5-(2-methoxycarbonyl-alky])-2,5-dihvdro-pyrazin (Michael-Addition) ailgemei-ne Arbeitsvorschrift1 ... 

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. 

Phthalimid N-[2-(Imidazol-4-yl)-ethoxy]- E16a, 238 (O-Alkyl.) Pyrazin 3-Amino-5-benzoyl-2-methoxycarbonyl- E9b/2, 324 (H - CO-Ar)... 

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