Pteridine, amination

Other types of dimer are formed from pteridin-6-one by the action of ammonia and hydrogen sulfide, giving rise to the corresponding dipteridinyl amine (55JCS2690) and sulfide (65JCS27) respectively. Two pteridine nuclei may be connected directly on base treatment... 

A great variety of differently substituted pteridine derivatives have been synthesized starting from (109) or the 2,4,6,7-tetrabromo compound (60USP2940972), which shows a corresponding reactivity pattern. Amines at low temperature substitute only the 6- and... 

Methyl 3-(triphenylphosphoranylideneamino)pyrazine-2-carboxylate 33 has been synthesised and used to obtain pteridines 34, 35 by reaction with isocyanates followed by adding alcohols or amines (Scheme 5)<96JCS(P1)247>. 

Nitropyridine yields a mixture of 2-, 4- and 6-amino-3-nitropyridines by this method142. An amino group is introduced into the 2-position of l,n-dinitronaphthalenes (.n = 3-8)143 and various 5- and 8-nitroquinolines, such as 8-methyl-5-nitroquinoline and 6-chloro-8-nitroquinoline, have been aminated adjacent to the nitro group144. Pteridines are converted into alkylarnino derivatives by the action of a solution of potassium permanganate in an alkylamine, e.g. equation 51145. 

Annelida Oligochaeta Mar. ALKAL. amines, pteridines pyrrole. Land Land... 

O -Benzylfolates, such as 230, have been investigated as inhibitors of DNA allyltransferase with some promise <2004JME3887> they can readily be prepared from 2,5,6-triamino-4-0-benzylpyrimidine by standard ring-forming condensation via the pteridine 6-aldehyde and reductive amination to insert the 4-aminobenzoyl glutamate. 

The investigations on the pyrido[2,3-6]pyrazine ring were inspired by the related pteridine ring, of importance in natural products. Pteridines are very reactive systems with both liquid ammonia and KNH2 in liquid ammonia, but in neither medium have anionic (j-adducts ever been detected. Such adducts presumably form initially and rapidly evolve toward covalent amination and ring contraction products.119,121... 

Of all the aza-heterocycles, pyridine possesses the least electron deficiency. Because of this, pyridine itself does not form a a-complex in liquid ammonia and cannot be aminated under these conditions. By the contrast, highly ir-deficient polyaza-heterocycles (diazines, triazines, tetrazines, pteridines, etc.) undergo oxidative amination, sometimes even by liquid ammonia itself. Sodamide converts 4-methylpyrimidine successively into the 2-mono- and 2,6-di-amino derivatives, and pyrazine gives... 

Pteridine and 2-chloropteridine were aminated by liquid ammonia (—40 °C) and potassium permanganate into the corresponding 4-aminopter-idines (86JHC473). Under these conditions no amino-dechlorination at C-2 was found. The regiospecificity of adduct formation is temperature dependent. At — 33 °C the C-4 adducts, i.e., the 4-amino-3,4-dihydro-2-R-pteridines (R = H, Cl), were formed as identified by NMR spectroscopy (Scheme 31). However, at temperatures up to 25 °C addition of ammonia takes place at positions C-6 and C-7, yielding the 2 1 a-adducts 6,7-diamino-5,6,7,8-tetrahydropteridines. Attempts to oxidize the C-6/C-7 diadduct into a 6,7-diaminopteridine were not successful (Scheme 31). 

Pteridine synthesis from pyrazine precursors are usually applied in such cases where the formation of special derivatives cannot be achieved easily by the pyrimidine approach. Methyl 3-amino-2-pyrazinecarboxylate (362) reacts with thiophosgene to give the corresponding 3-isothiocyanato derivative (363) which cyclizes with primary amines, arylalkylamines, aminoalcohols, amino acids,... 

Another key intermediate for pteridine synthesis was also seen in 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide which reacts with various amines to form the corresponding amides followed by cyclization with triethyl orthoformate giving 3-alkyl-6-phenyl-4(3/7)pteridinone 8-oxides <87JHC1109>. The synthesis of 2,4-diamino-6-methylpteridine 5-oxide (371) was achieved from 5-methyl-pyrazine-2-carboxamide (366) via the 4-oxide (367), a Hofmann degradation (368), bro-mination (369), and cyanation (370) followed by cyclization with guanidine to give (371) (Scheme 60) <93JHC841>. 

B-89MI 718-01 R. A. Levine, S. Milstien, D. M. Kuhn and H. C. Curtius Pteridines and Biogenic Amines... 

B-92MI 718-03 S. Muranishi and W. Pfleiderer in Pteridines and Related Biogenic Amines and Folates, ... 

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