Pyrimidinone derivative

Kistler KA, Matsika S (2007) Cytosine in context a theoretical study of substituent effects on the excitation energies of 2-pyrimidinone derivatives. J Phys Chem A 111 8708-8716... 

The hydroxymethyl derivatives 194 undergo one-pot intramolecular cyclization to form pyrimidinone derivatives 195 in excellent yields (Equation 18) <2006T1433>. 

While all of the above examples have involved pyrimidinone derivatives, pyrimidines themselves can also be reduced to dihydro derivatives using triethylsilane and trifluoroacetic acid <2004TL2107>. Thus, a variety of 2-aminopyrimidines 390 were reduced to their 1,6-dihydro derivatives 391 in good yield by treatment with trifluoroacetic acid (TEA) and triethylsilane at room temperature, while 5-bromopyrimidine 392 similarly gave the dihydro derivative 393 in 81% yield under the same conditions <2004TL2107>. 

The addition of organometaiiics to unactivated pyrimidines normally produces unstable dihydro derivatives which readily oxidize back to the pyrimidine oxidation level, although successful conjugate addition to pyrimidinone derivatives can occur. Thus, the addition of lithium trimethylsilyldiazomethane [TMSC(Li)N2] to 1,3-dimethyluracil 418 occurred at the 6-position to produce a mixture of the two pyrazolo[4,3-rf]pyrimidine-5,7-diones 419 and 420, where the initial addition had been accompanied by cyclization <1997T7045>. 

Other important pyrimidinone derivatives include temelastine 1123, an antihistaminic agent, urapidil 1124, an antihypertensive, and 5-hydroxymethyl-6-methyluracil (pentoxyl) 1125 which is used as a leukopoietic stimulant in wound healing. 

Invention Significance Pyrimidinone derivatives have been found... 

Table 1 Selected pyrimidinone derivatives and their corresponding mass spectral data. H NMR product characterization supplied by author...

In earlier, (I), and subsequent investigations, (II), by the authors (1,2), respectively, additional pyrimidinone derivatives were prepared, which were effective as serine protease inhibitors, and used in the treatment of thrombotic disorders. 

Fig. 1 Supramolecular polymer of bifunctional ureido pyrimidinone derivative reported by Lehn...

In addition to those of other monocyclic and bicyclic pyrimidinone derivatives, photolysis of hexahydropyrimido[l,2-a]azepin-4-ones was... 

Modica, M., Santagati, M., Russo, F., Parotti, L., Degioia, L., Selvaggini, C., Salmona, M. and Mennini, T. (1997). [[(Arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone Derivatives as High-Affinity, Selective 5-HTla Receptor Ligands. J.Med.Chem.,40,574-585. 

SKF 93479) is a pyrimidinone derivative, a HISTAMINE Hj-RECEPTOR ANTAGONIST. GASTRIC SECRETION INHIBITOR and ANTIULCEROGENIC AGENT. It has experimental antinociceptive activity. 

The X-ray crystal structures of a series of Dewar pyrimidones (151), obtained by the irradiation of the pyrimidones (152), have been determined. The photochemical reactivity of l-methyl-4,6-diaryl-2(///)pyrimidinone derivatives in the presence of various thiols has been studied. ... 

An electron impact mass spectrometric study of a tetrazolo[l,5-c]pyrimidinone derivative has been published <930MS643>. The fragmentation results are shown in Figure 1. These results revealed... 

A convenient catch and release methodology based on the PS-BEMP mediated sequestration was explored for the synthesis of 2-alkylthio-pyrimidinone derivatives... 

More recently, to find more effective methods to construct bis(heterocycle)s containing a pyrimidine ring from MBH derivatives, the solid-phase parallel synthesis of new annulated pyrimidinone derivatives was disclosed (Scheme 4.219). " The resin-bound allyl amine derivatives 742 were treated with cyanogen bromide to yield the pyrazole derivatives 743 in good yields under standard conditions. The subsequent lactonization with cleavage of the resin afforded the pyrimidinone derivative 744 in good yields in the presence of 20% triethylamine in chloroform under reflux. 

Later, the authors extended the scope of this reaction by utilizing MgO as an effective mediator in refluxing acetonitrile [74]. The reaction times could be reduced to 45-120min, while the yield was improved. The application of ethyl 2-cyanoac-etate 175 instead of malonodinitrile 21 led to pyrimidinone derivatives 177. Using phenylhydrazonopropane-2-one 179,... 

H. Sheibani, M. Seifi, A. Bazgir, Synth. Commun. 2009, 39, 1055-1064. Three-component synthesis of pyrimidine and pyrimidinone derivatives in the presence of high-surface-area MgO, a highly effective heterogeneous base catalyst. 

Example 6.2 Using parallel synthesis, a series of 4(3H)-pyrimidinone derivatives IV was prepared. According to previous knowledge from these compounds, anti-HIV activity was expected [15]. 

In the late 1990s de Mendoza et al. designed hybrids between calix[4]arene compounds and two cytosine-like amino-pyrimidinone derivatives (27 and 28) which are attached to the scaffold at the 1,3-positions. The resulting hybrids adopt a 1,3-alternate conformation and form non-covalent dimers with two sets of four intermolecular DDAA hydrogen bonds (Fig. 24.13). The dimeric complexes... 

Braun T, Foxon SP, Perutz RN, Walton PH (1999) Nickel-assisted carbon-fluorine bond activation of 2,4,6-trifluoropyrimidine synthesis of new pyrimidine and pyrimidinone derivatives. Angew Chem Int M 38 3326-3329... 

Arigon J, BroUo M, Clement J, Combet R, Durand F, El Ahmad Y, Labrosse J-R, Letallec J-P, Ronan B (2013) Pyrimidinone derivatives, preparation thereof and phrumaceutical use thereof. US2013/289031 (Al)... 

SCHEME 27 DAHP-catalyzed synthesis of substituted pyrano[2,3-d]pyrimidinone derivatives 18 in ethanol-water media [132]. DAHP, diammonium hydrogen phosphate. 

M. Ghashang, S. Sheik Mansoor, K. As win, Pentafluorophenylammonium triflate (PFPAT) catalyzed facile construction of substituted chromeno[2,3-d]pyrimidinone derivatives and their antimicrobial activity, J. Adv. Res. 5 (2014) 209-218. 

S. Balalaie, S. Abdolmohammadi, H. RezaBijanzadeh, A. Mohammad Amani, Diammonium hydrogen phosphate as a versatile and efficient catalyst for the one-pot synthesis of pyrano[2,3-d]pyrimidinone derivatives in aqueous media, MoL Divers. 12 (2008) 85-91. 

Hajipour et al. [251] prepared pyrimidinone derivatives 160 in good yield by reaction of aromatic aldehydes with cyclopentanone and urea or thiourea in the presence of [TEBSA][HS04 as the Bronsted acidic IL under thermal and solvent-free conditions (Scheme 86). The methodology was claimed to be advantageous in terms of short reaction times, straightforward workup, and reusability of the catalyst. Reaction of benzaldehyde, cyclopentanone, urea, and acidic IL when carried out in a molecular ratio of 1 1 1.2 0.15, respectively furnished good yield of products in the short reaction time. 

SCHEME 86 Synthesis of pyrimidinone derivatives using [TEBSAJPSOJ. 

A.R. Hajipour, Y. Ghayeb, N. Sheikhan, A.E. Ruoho, Bronsted acidic ionic liquid as an efficient and reusable catalyst for one-pot three-component synthesis of pyrimidinone derivatives via BiginelH-type reaction under solvent-free conditions, Syn. Commrm. 41 (2011) 2226-2233. 

Chloro-3,4-dihydronaphthalene-2-yl)methylene]amino -1 -phenyl-2-thioxo-1,6- dihydro[l,3]thiazolo[5,4-d]pyrimidin-7(2H)-one, which considered as a 7-thia analogue of the natural purine bases, adenine and guanine, was prepared in an excellent yield by condensing 189 with cyanoacetic acid hydrazide followed by Gewald reaction, by reaction of 190 with suhar and phenyl isothiocyanate in the presence of triethylamine as a basic catalyst to give 191(Scheme 84). Thiazolo[5,4-d]pyrimidinone derivative 192 was prepared by heating 191 with a mixture of triethylorthoformate and acetic anhydride (1 1) [117],... 

Intramolecular photocycloaddition is also reported to occur in the thiothymidine thymidinyl phosphates (80, R = H) and this gives the thietane (81) and the ring-opened thiol (82) (Scheme lO). The importance of this process is related to lesion in DNA. Irradiation of (80, R = Me) gives a new type of photoproduct (83) in the nucleic acid series that involves attack of the thiocarbonyl across the propene moiety of the thymidine ring. Irradiation at 366 nm in aqueous solution of the thiothymine (84) in the presence of adenine derivative (85) results in the formation of the adduct (86) this is formed presumably by way of the (2-l-2)-cycloaddition reaction between the C=S and the C=N bonds. Inter-molecular (2-i-2)-cycloaddition is also reported in the photoreaction of (84) with pyrimidinone derivative. Intramolecular photocycloaddition also occurs between thymine and 6-thioinosine derivatives tethered with ribose-phosphate-ribose and thietanes are obtained. ... 

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