Pyrano 2,3- / pyrimidines

Thiazolonaphthyridinium salts 331 can be produced either by bromination of the 2-alkenylpyridine precursor, or by thermal cyclization of the 2-(bromoacetyl)pyridine (Scheme 81) <1997CL1203>, and reaction of the pyrano-pyrimidine 332 with o-aminothiophenol gives the benzothiazole-fused pyridopyrimidinedione 333 (Equation 118) <2003JCCS887>. 

The pyrano[2,3-thio analogue may be made similarly (64JOC219). 

The one-pot MCR of methylene active nitriles 47 has been used in the synthesis of both pyrano- and pyrido[2,3-d]pyrimidine-2,4-diones in a single-mode microwave reactor [90]. Microwave irradiation of either barbituric acids 61 or 6-amino- or 6-(hydroxyamino)uracils 62 with triethyl-orthoformate and nitriles 47 (Z = CN, C02Et) with acetic anhydride at 75 °C for 2-8 min gave pyrano- and pyrido[2,3-d]pyrimidines in excellent yield and also provided a direct route to pyrido[2,3-d]pyrimidine N-oxides (Scheme 27). 

Scheme27 Synthesis of pyrano- and pyrido[2,3-d]pyrimidin-2,4-diones...

The hydrazine 70 reacts with triethyl orthoformate, sodium nitrite in acetic acid, or pyruvic acid, to yield l,2,4-triazolo[4,3-c]-, tetrazolo[l,5-c]- and l,2,4-triazino[5,6-c]pyrano [4 ,3 4,5]pyrrolo[3,2-e]pyrimidine derivatives 71(X= CH), 71(X= N) and 72 respectively <95KGS700 96CA(124)176023>. 

The synthesis of 4//-pyrano[2,3-d]pyrimidines, a class of compounds important in crop protection, is presented in Scheme 91. Dichlorotriphenyl-phosphorane affords iminophosphorane 247 with ethyl 2-amino-4//-pyran-3-carboxylate (246). Phenyl isocyanate cyclizes under alkoxide migration to afford pyrano[2,3-d]pyrimidines (248) (90LA995). 

In another approach (Scheme 92) enamino nitriles 249 serve as starting materials for pyrimidine syntheses. After transformation with triethyl orthoformate to 2-ethoxymethylenimino-3-carbonitriles (250), these are cyclized with semicarbazide to pyrano[2,3-d]pyrimidin-3-yl ureas (251). Dichlorotri-phenylphosphorane reacts in a second cyclization to give l,2,4-triazolo[l,5-... 

Prajapati D, Gohain M (2006) An efficient synthesis of novel pyrano 2,3-d - and furopyrano 2,3-d pyrimidines via indium-catalyzed multi-component domino reaction. Beilstein J Org Chem 2. Doi 10.1186/1860-5397-2-11... 

Attempts to obtain pyrano[3,2-d]pyrimidine 272 from guanidine and the corresponding pyrans failed. The products were diaminopyrimidines 273, products of recyclization (86JPR35) (Scheme 110). 

Dave and Shah have reported a Gould-Jacod type reaction for the microwave-assisted synthesis of thieno[3,2-e]pyrimido[ 1,2-c]pyrimidines via intermediate thieno[2,3-d ] pyrimidines (Scheme 3.46)73. A one-pot synthesis of pyrano [2,3-d]pyrimidines was also described by Kidwai and co-workers starting from thiobarbituric acids. The thio-barbituric acid intermediates were also prepared by microwave heating, using basic alumina as the solid support (Scheme 3.46)74. 

With triethylamine in methanol, 1,3-dimethylbarbituric acid (217) adds DMAD in Michael fashion to give 218, which, after heating to 170° or treatment with boron trifluoride etherate at 120° to 130° gave pyrano[2,3-[Pg.384]

A new, simple, synthesis of 2,4-diaryl-l, 3,5-triazines is shown in Scheme 1. It arose from an attempt to obtain the pyrano[4,3-rf]pyrimidine system by reacting aryl amidines with the 3-methoxymethylenedihydropyran-2,4-dione (1 X= CH2). As well as the desired products, diaryl-I,2,3-triazines were obtained in 30-40% yield. The use of 5-methoxymethylene-2,2-dimethyl-l,3-dioxan-4,6-dione (1 X= 0)(derived from Meldrum s acid) gives the triazines in better yield (> 50%). It was also observed that 3-methoxymethylenefuran-2,4-dione reacted with 5-methylisothiouronium bromide to yield 2,4-bismethylthio-l,3,5-triazine [95M99]. 

This synthesis involves Michael cycloaddition reaction of the readily available 4-hydroxycoumarine 1 with a cyanocrotonitrile 2 in ethanolic piperidine to afforded 2-amino-3-cyano-4-methyl-4H, 5H-pyrano-benzopyran-5-one (3). Treatment of 3 with acetic anhydride for 0.5 h and/or 3 h under reflux afforded N-acetyl and [l]benzopyrano[3/,4/ 5,6]pyrano(2,3-d) pyrimidine-6,8-dione derivatives (4) and (5a), respectively. Also, interaction of 3 with benzoyl chloride or formic acid gave the corresponding pyrimidine derivatives (5b,c) while its treatment with formamide afforded the aminopyrimi-dine derivative (6). 

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