2- -5-phenylpyrimidine

Ethoxy-6-methylpyrimidine 1-oxide (499) reacts with phenyl isocyanate to eliminate carbon dioxide and give a mixture of 4-ethoxy-6-methyl-N-phenylpyrimidin-2-amine (SOO) and (the derived) 7V-(4-ethoxy-6-methylpyrimidin-2-yl)-7V,7V -diphenylurea (SOI) phenyl isothiocyanate reacts quite differently (79CPB2642). 

The type of synthesis in which the two-atom fragment supplies C-5 + C-6 is uncommon but useful in preparing pyrimidine- and 5,6,7,8-tetrahydroquinazoline-2,4-diamines. Thus, dicyandiamide (S78) with benzyl methyl ketone (S77) yields 6-methyl-5-phenylpyrimidine-2,4-diamine (S79), or with acetophenone it yields 6-phenylpyrimidine-2,4-diamine (62JOC2708). Likewise, with cyclohexanone it yields the tetrahydroquinazolinediamine (SSO) and by using N- substituted dicyandiamides, 2- and/or 4-alkylamino groups may be introduced (65JOC1837). 

Several triazinyl ketones isomerize to 4-acetamidopyrimidines. TTiis is seen in the C-acylation of 2,4,6-trimethyl-l,3,5-triazine (708) with benzoyl chloride in the presence of sodium amide to give the ketone (709) which undergoes a Dimroth-like rearrangement in boiling water to afford A-(2-methyl-6-phenylpyrimidin-4-yl)acetamide (710) it can be seen that the acylating agent determines the identity of the 6-substituent 64JHC145). 

Phenylpyrido[4,3-d]pyrimidin-o(677)-ones (145) have been prepared from 7-phenylpyrano[4,3-d]pyrimidin-5(6/7)-ones (144) by treatment with ammonia, hydroxylamine, or hydrazine at room temperature. The utility of the route lies in the rapid preparation of 4-methyl-2-phenylpyrimidine-5-carboxylic acid (143) from cheap... 

Cyanine dyes have been prepared from the salts obtained by the quatemization of 4,6-dimethyl-2-phenylpyrimidine and 2-alkyl- or 2-aryl-4,6-dimethylthiopyrimidines, but there can be no ambiguity in the structure of these quaternary salts. 

Other examples of CN/CC replacement are observed in reactions of l-phenyl-pyrimidin-2(l//)-one with active methylene compounds, such as diethyl malonate and benzoylacetate, giving in good yield 2-oxo-l,2-dihydro-3-pyridinecarboxylate and 3-benzoylpyridin-2(l H)-one, respectively (84CPB2942, 87H2223) (Scheme 8). In a similar way 4,6-dimethyl-1-phenylpyrimidin-2( 1 //)-one, 4,6-dimethyl-1 -phenylpyrimidine-2( 1 //)-thione and 4,6-dimethyl-1 -phenyl-2-phenylimino-1,2-dihydropyrimidine yield with malonitrile 2-amino-4,6-dimethyl-3-pyridinecarbonitrile. In a similar way 2,3-diarylpyrimidin-4(3//)-thiones give with malonitrile CN/CC replacement (84H763) (Scheme 8). The reaction takes a similar course as described in Scheme 7. 

Benzyl-9-phenyl-3,4-dihydro-27/,677-pyrimido[6,l-A [l,3]thiazine-6,8-(7//)-dione was prepared from 3-benzyl-6-chloro-l-(3-chloropropyl)-5-phenylpyrimidine-2,4-(17/,3//)-dione and NaSH hydrate in DMF in 27% yield <1995W035296>. 

This was later extended to the synthesis of novel pyrimido-[l,3-a]-pyrimidines under solvent-free conditions ethyl-2-armno-4-aryl-l,4-dihydro-6-phenylpyrimidine-5-car-boxylates react regioselectively with 3-formyl chromone or diethyl (ethoxymethylene) malonate, without solvent, to afford pyrimido-[l,3-a]-pyrimidines [92] (Scheme 8.66). 

Abstract. The direct scale-up of a solid-phase synthesis has been demonstrated with 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide and an arylsulfonamido-substituted hydroxamic acid derivative as examples. These compounds were obtained through combinatorial chemistry and solution-phase synthesis was used in parallel to provide a comparison. By applying highly loaded polystyrene-derived resins as the solid support, a good ratio between the product and the starting resin is achieved. We have demonstrated that the synthesis can be scaled up directly on the solid support, successfully providing the desired compounds easily and quickly in sufficient quantities for early development demands. 

The above-described formalism is applied to the typical calamitic (rodshaped) mesogen PYP 906 (2-[4-(hexyloxy)phenyl]-5-nonylpyrimidine, 1) in Figure 8.3. PYP 906, the prototype of the class of phenylpyrimidine LCs, which form the foundation of most commercial SmC materials, possesses the phase sequence on heating X-SmC-SmA-N-I, where X is a crystalline... 

Pyrimidinylzinc chloride 22 was generated in situ by halogen-metal exchange of 5-bromo-4,6-dimethoxypyrimidine (21) with n-BuLi followed by treatment with ZnCl2 [15]. The subsequent Negishi coupling of 22 with 3,4-dinitrobromobenzene gave phenylpyrimidine 23. 

The amino-debromination of 6-bromo-4-phenylpyrimidine (Scheme 1.3). The reaction has been proved to occur by the formation of an initial ct-adduct at C-2, which subsequently rearranges into the 6-amino product [Sn(ANRORC) mechanism]. 

Similar experiments were carried out with 6-bromo-5-deuterio-4-phenylpyrimidine. When subjected to treatment of potassium amide/liquid ammonia, it was observed that the 6-aminopyrimidine did not contain deu-... 

However, when 6-bromo-4-phenylpyrimidine reacts with lithium piperi-dide/piperidine instead of potassium amide/liquid ammonia, it was surprisingly found that the corresponding 4-phenyl-6-piperidinopyrimidine was not obtained. Rather, the product was a compound whose structure was established to be a Z/E mixture of 2-aza-4-cyano-3-phenyl-l-piperidino-1,3-butadiene (2) (70RTC129). The presence of a cyano group in structure... 

As we have seen in Section II,A, 6-bromo-4-phenylpyrimidine reacts on treatment with potassium amide in liquid ammonia at -75°C into the corresponding 6-amino compound nearly quantitatively according to the Sn(ANRORC) mechanism (71RTC1239). Extensive investigations have been carried out on the scope and limitations of this mechanism and on the several factors that influence the occurrence of the Sn(ANRORC) mechanism in the aminodehalogenation of 4-substituted-6-halogenopyrimidines. 

The nature of the leaving halogeno atom. It has been observed that reaction of mono-labeled 6-fluoro-, 6-chloro-, and 6-iodo-4-phenyl[l(3)- Njpyrimidine with potassium amide/liquid ammonia leads to 6-amino-4-phenylpyrimidine in which the exocyclic amino group is N-labeled the percentages, however, strongly depend on the nature of the halogen atom, i.e., F (73 5%), Cl (93 5%), Br (83 5%), I (13 5%) (Scheme 11.12) (72RTC1414). 

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