Pyrimide

There are few examples of [5 + 1] cyclizations from pyrimidine intermediates. Two of these involve the chloropropionic ester (194), which gives the 5,6,7,8-tetrahydro-7-one (195) with ammonia (59JCS1849), and the cyclization of a 4-ethynylpyrimidine-5-carboxylate with ammonia to give a pyrido[4,3-. In a recent patent, 5-ethoxycarbonylpyrimidin-4-yl-j8 -alanine derivatives are cyclized with ammonia to pipemidic acid analogues (80GEP2903850). One-carbon pyrimidine [5 +1] syntheses are included in Section 2.15.5.5.1 above. 

The antitrichomonal compound l-methyl-5-nitro-2-(2 -pyrimidyl)imida-zole (97 R = Me, R2 = pyrimid-2-yl) has been shown to be metabolized to the corresponding acetamide (118 R1 = Me, R2 = pyrimid-2-yl, R3 = Me) in both rats and humans (74JPS293). The acetamide (118 R1 = Me, R2 = pyrimid-2-yl, R3 = Me) was also produced synthetically by reduction of a solution of the nitroimidazole (97 R1 = Me, R2 = pyrimid-2-yl) in acetic acid with zinc powder and subsequent treatment of the aminoimidazole (96 R1 = Me, R2 = pyrimid-2-yl) in situ with acetic anhydride to give the acetamide (118 R = Me, R2 = pyrimid-2-yl, R3 = Me) (4%) (74JPS293). 

The reactions of4-(ethylamino)-2-(4-substituted piperazin-l-yl)pyrimid-ines and isopropylidene methoxymethylenemalonate (420) in THF at 25°C for 20 hr yielded yV-ethyl-/V-(4-pyrimidinyl)aminomethylenemalonates (430) in 71-82% yields [81JAP(K)99480, 81JAP(K)103178 83JAP(K)-46084],... 

Tab. 8.1 Overview over pyrid-2-yl- and pyrimid-2-yl-ligands used for immobilization.

Microwave technology has also been used for the Dimroth rearrangement of the aminothiazine 964 to the pyrimid-inethione 965. The optimized conditions involved heating a solution of the thiaztne 964 in toluene together with a silicon carbide heating element at 220°C for 30min to provide a 68% product yield after recrystallization <2006JOC4651>. 

Photolysis of the pyrimid-2-one (796) gives a diazabicyclohexanone which can be thermolyzed as shown in equation (97) to give quinolines (80TL2825). Another diazabicyclohexanone is invoked as an intermediate in the conversion of the zwitterions (797) into quinol-4-ones (75S247) an alternative pathway can give 4-hydroxyquinol-2-ones (79CB3424). 

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). 

Importantly, the ERCCl/XPF structure-specific nuclease has an additional role in the repair of cisplatin adducts besides its function in NER the recombinational repair of interstrand crosslinks (19). ERCCl- or XPF-deficient hamster mutant cell lines are hypersensitive to DNA crosslink agents, much more so than to ultraviolet-induced pyrimide dimers, the classical substrates for NER (20,21). Moreover, co-localization of ERCCl foci and RAD51 foci in response to cisplatin treatment has recently been found and may represent recruitment of ERCCl/XPF to sites of recombination repair (22). Previous studies have shown that BRCAl, involved in homologous recombination repair, also plays a major role in the repair of cisplatin DNA damage (23). 

The tetramer is the main polymerization product obtained (21% yield) on addition of hydroxide ion (3 days, 25°C, pH = 3.8) to solutions of the pure dimer (11, 70, 79). On acidification, the tetramer splits into [Cr(OH2)6]3+ and the trimer. Careful investigation of the tetramer showed that two rapidly interconverting species could be detected (Fig. 10). The proposed structure of TC (80), with a square pyrimidal tetraco-... 

Basal ganglia lie beneath the cortex and have effects on muscle tone and posture especially in involuntary motor movement. (This is called the extrapyrimidal motor system. The voluntary motor system is referred to as pyrimidal.)... 

Unfortunately, it is not possible to determine the maximum vibrational energy content of the methyl radicals produced in the photolysis of methyl iodide. On the basis of the arguments outlined above, strong excitation of the C-H stretching vibration would probably not be anticipated. The methyl radical is planar, however,36 so that its deformation vibration would be excited. On the other hand, the halomethyl radicals are believed to be pyrimidal,37 and unless the grouping has a planar configuration in the excited parent polyhalomethane, deformation would not make any appreciable contribution to the vibrational excitation of the radical. 

Polymer-assisted methodology has been used several times for parallel-array synthesis of libraries involving three to five synthetic steps. Scheme 11 shows a three-step solution-phase synthesis of 2-thioxo-4-dihydro-pyrimid-inones wherein the key purification step involved amine resin 1 to sequester excess aldehydes and isot,hiocyanates from upstream transformations. Thermal cyclization of the purified intermediates gave the desired 2-thioxo-4-dihydropyrimidinones in excellent yields and purities.83... 

Related metalations (n-BuLi) of 6-chloro-2,4-dimethoxypyrimidine (C-5 TMS and C-5 SnMe3 products) [88JOM(342)l] has also been done. 5-Methoxy, as well as 2,4,4,6-dimethoxy, and 2,4,6-trimethoxy pyrimides were lithiated under similar conditions (LiTMP/THF/-78°C), leading respectively to the 4- and 5-substituted derivatives in medium to high yields (90JOC3410). 

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). 

Pyrrole (1) has a pentagonal structure of C2v symmetry having all the atoms in a single plane. The orbital hydridization18 of the nitrogen atom approximates to sp2, although the possibility of a pyrimidal hybridization, i.e., sp2 sp3, was originally considered. Dipole moment studies allow the N-H bond an out-of-plane latitude of 7° (see Section... 

---