Pyrimido pyrimidinones

Guo T, Hunter RC et al (2007) Microwave assisted synthesis of isothiazolo-, thiazolo-, imidazo-, and pyrimido-pyrimidinones as novel MCHIR antagonists. Tetrahedron Lett 48 613-615... 

Diamino-4(3/f)pyrimidinones on reaction with a-diketones give (84JHC1537 85JHC1317) pyrimido[l,2- ][l,2,4]triazines 240. Similarly, the condensation of 2,3-diamino-4(3i/)pyrimidinones with cyclohexandi-one, 1,2-naphthoquinone, acenaphthenequinone, and phenanthraquinone gives the respective condensed pyrimidotriazines of general structure 241 (85JHC1317). 

Rearangement of furoxans leads to the formation of new heterocyclic systems derivatives of triazoles, diazoles, isoxazoles, and pyrimidinones. For example, on the basis of the experimental results using labeled compound 52-15N , the formation of 8-phenyltheophylline 53, the 1,3-dimethylalloxazines (54 n = 0, 1), and l,3,7,9-tetramethyl-l//,9//-pyrimido[5,4-g]-pteridine-2,4,6,8-tetraone 55 in the thermal reaction of the iV-oxide 52 with benzylamine, aniline, or piperidine and the generation of NO or NO-related species in the reaction with iV-acetylcysteamine were reasonably explained by... 

The preparation of pyrimido[4,5-f][l,2]oxazines by intramolecular displacement of a triazole from position 4 of a 2-pyrimidinone was described in CHEC-II(1996) <1996CHECTI(7)768>. This approach has since been used for the preparation of a number of nucleoside analogues containing this ring system <1997W097/28177, 2001NN1049>. 

Phenyl-2//-pyrimido[ 1,2-b]pyridazin-2-one (71) is cleaved by reaction with potassium isopropoxide in refluxing isopropyl alcohol to give the pyrimidinone (72) (72M1591). 

Reaction of 2-amino-4-pyrimidinone (229) with an excess of acrylonitrile gives the intermediate (230). This intermediate can be cyclized to the product (231) in excellent yield by heating in glacial acetic acid (6UOC1891). Similarly, 3,4-dihydro-6,8-dimethyl-pyrimido[ 1,2-a ]pyrimidin-2-one hydrobromide (233) is prepared by the reaction of 2-amino-4,6-dimethylpyrimidine (232) with 3-bromopropionic acid. This reaction also proceeds via a pyrimidinylpropionic acid intermediate (61JOC1891). 

Heating a well-mixed mixture of l-(2-hydroxyethyl)-2-ethoxycarbo-nyl-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline and solid NaOMe at 130 °C for 45 min followed by extraction of the reaction mixture with EtOAc provided 9,10-dimethoxy-1,6,7,11 b-tetrahydro-2H,4H-[l, 3]oxa-zino[4,3- ]isoquinolin-4-one in 52% yield (09T8021). 1,3,4,6,7,11b-Hexahydro-2H-pyrimido[6,l-fl]isoquinolin-4-one 53 was obtained from pyrimidinone 91 by a Pictet-Spengler reaction in CH2C12 in the action of TFA at ambient temperature (09OL1559). 

Matyus et al. reported the synthesis and cardiotonic activity of pyrimido[5,4-6][l,4]oxazinones <90JHC151>. The synthesis started from 6-amino-2,3-dimethyl-4(3//)-pyrimidinone. Also 4-sub-stituted pyrimido[5,4-6][l,4]oxazinones were transformed into pharmaceutically interesting products. Several compounds were prepared some showed an ionotropic effect, for example (208) and (209). 

These compounds are also known as thiapteridines. Most syntheses of pyrimido[5,4-/>] [l,4]thiazines were developed for pteridines and then adapted for the thio analogues. Thus, the cyclization of polyfunctionalized pyrimidinones (e.g. (268) - (269)) is a well-known method (Equation (41)) <92H(34)729>. 

Pyrimido[3, 2 4,5]thieno[3,2-(/]pyrimidinones reacted with hydrazonoyl halides in dioxane and triethylamine to give the corresponding tetracyclic fused tetrazines <06JHC935>. 

Amino-4-carboxamidopyridazine can be obtained in high yield by aqueous base hydrolysis of 4(3//)-pyrimido[4,5-c]pyridazinone (Equation (43)). The pyrimido[4,5-c]pyridazinone, which is readily prepared from 6-hydrazino-4(3/ -pyrimidinone by condensation with glyoxal sodium bisulfite followed by treatment with trifluoroacetic acid, is even hydrolyzed in boiling water. This lability is shared by some derivatives <85JOC346>. 

An analogous reaction of the pyrimidinone (156) with triethyl orthoformate in trifluoroacetic acid gave the pyrimido[4,3-d]pyridazine (158) (78JOC2536). 

A crystalline inclusion complex of 10-(4-f-butylphenyl)-3-(2-ethyl-phenyl)-pyrimido[4,5-fc]quinoline-2,4(3H,10H)-dione/urea/EtOH obtained. X-ray analysis showed that the urea is doubly H-bonded to the pyrimidinone (96TL8905). The proximity of the chiral axis might give interesting applications in chiral recognition. The enantiomers were involved in an enantioselective hydride transfer reaction (Figure 25). 

Pyrimidinone ring from o-aminocarboxylic acid amides via o-acylaminocarboxylic acid amides Pyrimido[4,5-b][l,8]naphthyrid-4(3Il)-ones... 

Ferraritii PL, Mori C, Primofiore G, Calzolari L (1990) One step synthesis of pyrimido[l,2-rj] [l,8]naphthyridinones, pyrido[l,2-a]pyrimidinones and 1,8-naphthyridinones. Antihypertensive agents. V. J Heterocycl Chem 27 881-886... 

Tetrahydro-2H-6H-pyrimido[2,l-b]-l,3-oxazine-2,4-diones from tetr ahy dro-1 -malonyl-2 (IH) -pyrimidinones... 

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