Pyrimido pyrazines

The fused system, pyrimido[4,5-h]pyrazine (219), is more commonly known as pteridine, a ring system which is present in such biologically important molecules as alloxazine, riboflavin, leucopterin, xanthopterin, and the coenzyme, flavin-adenine dinucleotide. 

A test library with three novel p38a inhibitory activity has been prepared, among them pyrazolo[3,4-c/]pyrimidine and pyrazolo[3,4-h]pyrazine with potent in vivo activity <06BMCL262>. A convenient route for the synthesis of pyrazolo[3,4-<7]pyrimidine involving Friedlander condensation of 5-aminopyrazole-4-carbaldehyde with formamide or benzamide has been reported <06JHC1169>. A facile synthesis of pyrazolo[3,4-<7]pyrimidines and pyrimido[4,5-<7]pyrimidin-4-one derivatives has been published <06SC2963>. 

Selective reduction of the 7-oxo group in pyrido[23-synthetic approach to 5,10-dideazatetrahydrofolic acid <00H(53)1207>. Cycloaddition of pyrimido[4,5-c][l,2,5]oxadiazine 96 with 2,3-dihydrofuran affords a new synthesis of dimethyllumazine derivative 97 which undergoes a ring-opening reaction to give pyrazine derivative 98 <00JHC419>. 

The one-step synthesis of further tri- and tetracyclic pteridine derivatives from 2-aminopyrazine 153 has also been described <2001JHC1173>. Cyclic analogues of A -[bis(methylthio)methylene]amino reagents such as 2-(methylthio)-2-thiazoline, 5,6-dihydro-2-(methylthio)-4//-l,3-thiazine, 2-(methylthio)-2-imidazoline, 2-(methylthio)-l,4,5,6-tetrahydro-pyrimidine, 2-(methylthio)-2-pyrazine, and 2-chloropyrimidine reacted with aminopyrazine 153 to afford thiazolo/thia-zino[2,3-3]- 159 ( = 1 (53%), n = 2 (42%)), imidazo/pyrimidino[2,l-/ ]- 160 ( = 1 (53%), = 2 (57%)), pyrazino[2,l-/ ]-161 (21%), and pyrimido[2,l-/ ]-pteridine 162 (42%) derivatives, respectively. 

Pyrimido[5,4-c]-l,2,5-oxadiazinones (417) are suitable starting materials to construct annulated pyrazines. Reaction with carbanions derived from CH-acidic compounds, activated by two different electron-withdrawing functions, proceed in a regioselective manner by initial attack at the N—O bond. Triethyl phosphonoacetate, /f-ketophosphonates, nitro ketones, nitro esters, sulfonylacetates, and JV-acetoacetylglycine have been applied to form 6,7-disubstituted lumazines (418) (Equation (18)) <91H(32)79>. 

Thirteen diazinodiazines without bridged heteroatom are theoretically possible. All of these have been reported in the literature. There are (i) four pyridazinopyridazines, namely pyridazino-[4,3-c]pyridazine (A), pyridazino[3,4-c]pyridazine (B), pyridazino[4,5-c]pyridazine (C), and pyridazino[4,5-[Pg.738]

Pyrazin 3-Amino-2-cyan-5-(2-furyi)-E9b/2, 31 If. (N-Oxid-Red.) lH-Pyrazol 4-Diazo-5-oxo-3-phenyl-4,5-dihydro- X/4, 525/ El4b, 1114 (Amin 4- NaN02) lH-(Pyrimido 5,4-f]indazol) 5(bzw. 9)-Hydroxy- E8b, 849 (Pyrimidin-Ringschl.)... 

The aminouracil derivative (259) condenses with dimethylformamide diethyl-acetal to the dimethylaminomethyleneamino compound (260) the thermolysis of which leads to the pyrimido(4,5-b)pyrazine (26/)104 ... 

The methods most frequently used to synthesize these compounds are [6 + 0(a)] cyclizations. Ring closures may take place via intramolecular alkylation, condensation, or nucleophilic substitution. The starting materials for the cyclizations in the case of pyrazino-oxazines are always pyrazine derivatives. Only a few representatives of these systems have been prepared. Pyrimido-oxazines are the most explored group of compounds. In the bicyclic series, cyclizations have been carried out in most cases from pyrimidine intermediates and only rarely from morpholino intermediates. For the preparation of benzo-fused derivatives, both benzoxazine and quinazoline intermediates have been used. Pyrazino-oxazines represent a small group of compounds. For cyclizations, both pyrazino and oxazino intermediates have been used. There are many lactone structures among these compounds. For their preparation, the usual methods of lactone formation have been applied. 

The ring fused onto the parent has the suffix o common names are used (with modification) where possible to simplify the name. Some examples are pyrido for pyridine, pyrrolo for pyrrole, thieno for thiophene, furo for furan, imidazo for imidazole, pyrimido for pyrimidine, pyrazino for pyrazine, among others. 

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