6-Pyrimidones ring synthesis

A synthesis of sildenafil, which contains a bicyclic system (a l//-pyrazolo[4,3- f pyrimidine) isomeric with that of a purine, starts with a routine synthesis of a pyrazole (cf. 25.12.1.1) followed by M-methylation and ring nitration. Functional group manipulation provides a pyrazole equivalent to AICA (27.11.1.2) from which the pyrimidone ring is formed via reaction with an aromatic acid chloride. 

Representative of recent applications of the reaction to the synthesis of heterocycles are the photodehydrochlorination of chlorobenzo[b]thiophen (347) to give the fused pyrimidone 348,287 the photoelimination of HI from iodobenzene derivatives 349 to give the benzazepines 350,288 and the synthesis of the medium ring aza-heterocycle 351 by irradiation of the chloro precursor 352.289 Included among the many other examples of... 

Synthesis of primidolol (65) can be carried out by a convergent scheme. One branch consists in application of the usual scheme to o-cresol (62) ring opening of the intermediate oxirane with ammonia leads to the primary amine (63). The side chain fragment (64) can be prepared by alkylation of pyrimidone (63) with ethylene dibromide to afford Alkylation of ami noalcohol with halide ... 

Intramolecular addition to aromatic systems also occurs and De Keukeleire and coworkers have described a fascinating example of such a process. In their example the pyrimidone unit adds to the 1,2-positions of a benzene ring. This reaction takes place in the molecule (170) and occurs with full chemo-, stereo-and regio-selectivity affording the single stable adduct identified as (171). Intramolecular addition is also reported for the pyrimidine derivative (172) which on irradiation at 300 nm in acetone/acetonitrile yields two adducts in a ratio of 4 1 of the general structure (173). The major isomer was isolated by transesterification and was identified as (174). This result is claimed to be the first synthesis of a cis-jy/i-furanoside (2+2)-cycloadduct. ... 

In the synthesis of lipoprotein-associated phospholipase A2 inhibitors reported by Smith and coworkers, the pyrimidonc rings of 24 originated from the condensation of amines with acylisothiocyanate 23 <01BMCL701>. No yields were reported in these transformations. Using similar chemistry, it was also reported that vinylogous carbamate 25 cyclized to fused pyrimidones 26 upon reaction with an isocyanate, isothiocyanate, or dilhioketal <01H115>. 

Hydroxyl groups substituted at positions 2- and 4-(6-) of the pyrimidine nucleus exist mainly in the pyrimidone form [1-4]. The only true hydroxyl position on this ring system is position 5. This hydroxyl group is of phenolic character and all 5-hydroxypyrimidines give a positive (blue-violet coloration) test with ferric chloride. Because of the relative difficulty in synthesis of all but a few compounds, most 5-hydroxypyrimidines have not been extensively studied. 

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