Pyrimid-4-ones

Table 25 Synthesis of imidazo[4,5-c]pyridines and pyrido[3,2-c/ pyrimid-4-ones (Equation 45) <2003JOC4345>...

Bicyclic /3-lactams have been produced by photochemical closure of the 3,4-bond on the irradiation of pyridone (155) and related derivatives (72CB2780, 72TL3563). In the case of pyrimid-4-ones (156) in alcoholic solution, the intermediate bicyclic azetine (157) undergoes ring opening (79JOC2083, 80JOC936). 

TV-Acylation of (73) can be achieved with acyl chlorides and pyridine or triethylamine, or with ketene (75S547 p. 560). 7V-Trimethylsilylazetidin-2-ones have been reported to undergo acyldesilylation on treatment with acetyl chloride. Acylation of (73) with imidates (78) at 150-160 °C was followed by ring expansion to give the pyrimidin-4-ones (79). Pyrimid-4-ones were obtained from a similar reaction of imidates with 4-alkoxyazetidin-2-ones (74CB270). Acylation with subsequent ring expansion also occurs with dithioimidates (73CPB1305). 

However, when 36 was heated with a-amino heterocycles or with cyclic 1,3-dicarbonyl or potential 1,3-dicarbonyl compounds, 3-heteroarylp)rr-azol derivatives were obtained. In this manner 36 afforded, when heated with 2-aminopyridine and 3-amino-lH-pyrazol in acetic acid under reflux for 2 h and 5 h, respectively, 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-4H-pyrido[l,2-fl]pyrimid-4-one (38) and 6-(5-ethoxy-l-phenyl-lH-p5rrazol-3-yl)pyrazolo[l,5-fl]pyrimid-7(lH)-one (39) in 70% and 77% 5deld, respectively. Similarly, 36 afforded with cyclicjS-dicarbonyl compounds, such as 4-hydroxy-6-methyl-2H-pyran-2-one and 5,5-dimethylcyclohexane-l,3-dione by heating in acetic acid for 4 h and 8 h, respectively, the corresponding 3-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl)-7-methyl-2H,5H-pyrano[4,3- 7]pyran-2,5-dione (40) and 3-(5-ethoxy-l-phenyl-IH-pyrazol-3-yl)-7,7-dimethyl-7,8-dihydro-2H-chromene-2,5-dione (41) in 26% and 82% yield, respectively (Scheme 15). 

Tucd FC, Zhu YF, Guo Z, Gross TD, Connors PJ Jr, Struthers RS, Reinhart GJ, Wang X, Saunders J, Chen C (2002) A novel synthesis of 7-aryl-8-fluoto-pyrrolo[l,2-a]pyrimid-4-ones as potent, stable GnRH receptor antagonists. Bioorg Med Chem Lett 12 3491-3495... 

In another work, fluoromethyl group in pyrimidines 1225 acted as CH-acid in an intramolecular condensation with carbonyl compound, leading to the formation of 8-fluoro-pyrrolo[l,2-a]pyrimid-4-one derivatives 1226 (Schane 268) [358,756],... 

Scheme 268 Synthesis of 8-fluoro-pyrrolo[l, 2-a]pyrimid-4-one derivatives 1226...

Pyrido[l,2-a]pyrimidinium salts, dehydro- 14, 517 Pyrido[l,2-a]pyrimid-4-ones... 

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