Pyrimidines polymer-bound

The successfully generated chalcones could be cleaved by treatment with trifluoro-acetic acid or used for the subsequent synthesis of pyrimidines [45], Condensation of the polymer-bound chalcones with benzamidine hydrochloride under microwave irradiation for 30 min furnished the corresponding pyrimidines in good yields after TFA-induced cleavage. This new robust support/linker system for SPOT synthesis has been demonstrated to be compatible with a range of organic reactions and highly applicable for microwave conditions. 

The capture of 4,6-dichloro-2-(methylthio)pyrimidine (8) was performed in DMF with diisopropylethylamine (DIPEA, Huenig s base) as a base and tetrabutylammonium bromide as a catalyst at 90°. The substitution of the remaining chlorine atom on the polymer-bound scaffold requires harsher conditions. Thus the immobilized 6-chlorothiomethylpyrimidine (9) could be substituted with aliphatic amines in neat amine at 140°. The coupling with anilines could be afforded consistently only by using KO Bu as base and [18]crown-6. Also, the use of Pd catalysts gave positive results, but failures were observed occasionally. Finally, the substitution of the thiomethyl group in resin-bound 2-(methylthio)pyrimidine-4,6-diamines... 

A novel and versatile solid-phase synthesis of pyrimido[4,5- fJpyrimidine-2,4-diones has been reported <03S1739>. The key step is the reaction of the support-bound pyrimidine with isocyanates, involving formation of a carbamate intermediate, followed by a base-catalyzed intramolecular ring closure to give the polymer-bound pyrimidopyrimidines which are used in subsequent reactions providing 1,3-disubstituted 7-amino derivatives. 

Multicomponent reactions have been described for several syntheses of imidazoles. Highly efficient methods for the syntheses of spiroimidazolinones via microwave-assisted three-component one-pot sequential reactions or one-pot domino reactions have been described <06JOC3137>. Multicomponent reactions between 2-aminopyrimidine, aldehydes and isonitriles afforded imidazo[l,2-a]pyrimidines <06TL947>. Two novel one-step microwave mediated syntheses of arrays of 3-iminoaryl-imidazo[l,2-a]pyridines and imidazo[l,2-a]pyridyn-3-ylamino-2-acetonitriles were synthesized by multicomponent reactions under microwave condition in methanol by simply mixing a-aminopyridines, aldehydes, and trimethylsilylcyanide catalyzed by polymer-bound scandium triflate <06TL2989>. 3-Aminoimidazo[l,2-a]pyridines have been synthesized via the multicomponent reaction of aldehydes, isocyanides and 2-aminopyridines in the presence of the ionic liquid l-butyl-3-methylimidazolium bromide [bmim]Br<06TL3031>. 

Obrecht described the reaction of resin-bound thiouronium salt 111 vrith oxophe-nylbutynoic acid tert-butyl ester. Cleavage from the support was effected by S-oxidation to the sulfone followed by displacement vrith an amine [132]. The thiouronium salt pathway is illustrated in Scheme 26. Later, Masquelin et al. developed a condensation of resin-bound thiouronium salts with methylenemalononitriles to provide polymer-bound alkylthiopyrimidines 110 [133]. Pyrimidine derivatives 112... 

Marzinzik and Felder [34] used polymer-bound enones which were generated from 4-carboxybenzaldehyde immobilized on Rink amide resin for the synthesis of pyrimidines and pyrimidones.The enones were then treated with different amidines in DMA for 16 h at 100°C (Fig. 6.25). 

Synthesis of 3-substituted 6-arylbenzo[r/][l,2,3]triazin-4(3/f)-ones using polymer bound triazenes has been reported <04JCO38>. Gas-phase thermolysis of thieno[3,2-e][l,2,4]triazines yielded benzonitrile, isothiazole, pyrimidine, [ 1 benzothieno[2,3-dJpyrimidine and thieno[3,2-rf thiazole derivatives. These products were separated by HPLC and column chromatography and characterized using GCMS, LCMS, H, C-NMR and 2D NMR spectroscopy... 

In a related and more recent study a variety of solid-supported acylating agents were synthesized and used for microwave-mediated transformation of amines, alcohols, phenols, and thiophenols [123]. In a microwave-mediated procedure, Mer-rifield resin was first modified by attaching 1,4-butanediol to introduce a spacer unit. Bromination and subsequent reaction with commercially available 6-methyl-2-thiouracil then treatment with corresponding acyl chloride afforded the desired polymer-bound pyrimidines (Scheme 16.81). The acylating ability of this supported reagent has been proven by reaction with benzylamine. 

Pyrimidines are an interesting class of nitrogen-containing heterocycles which display a broad range of useful properties.Based on a novel cyclocondensation reaction between acetylenic ketones of type 339 and polymer-bound isothiourea 338, Obrecht et developed a versatile and efficient solid-phase synthesis of polymer-bound 2-(alkylthio)-4,6-disubstituted pyrimidines 340, and combined this protocol with the nucleophilic displacement reaction of the 2-sulfonyl group of pyrimidines 47 j gy dgavage reaction. In addition, simple... 

One limitation encountered so far was the well known lack of reactivity of aromatic aldehydes and isonitriles under the Ugi conditions. The scope of this method was further extended by introduction of a third substituent at the 2-position of the pyrimidines. Thus, polymer-bound sulfones 348 were subjected to multidirectional cleavage with one equivalent of different nucleophiles affording compounds 350 in good yields and high puritiesl (Scheme 4.6.7). 

A similar approach towards the synthesis of pyrimidines was recently described by Suto et a/.i starting from polymer-bound thiol 351 as decribed in Scheme 4.6.8. 

Masquelin et took advantage of a similar strategy (Scheme 4.6.9). Thus, polymer-bound isothiourea 338 (Scheme 4.6.5) was treated with the commercially available bis-acceptor building block 361 to yield cleanly polymer-bound 6-amino-5-cyano-pyrimidine 362. This versatile building block was cleaved after oxidation with wi-CPBA with amines to yield diamino-pyrimidines of type 363. 

Other bases such as pyridine, lutidine, Et3N, polymer-bound 2,6-di-t-butyl-4-methylpyridine, and 2,4,6-trialkyl-substituted pyrimidines were also used. The commercially available IV,iV-diisobutyl-2,4-dimethyl-3-pentylamine is a very convenient base to prepare the vinyl triflates. In the case of nonfunc-tionaUzed ketones, anhydrous Na2C03 has been proved to be very successful. ... 

Combinatorial synthesis of substituted pyrimidines using the polymer-bound thiour-onium salt 1 has also been described by Srivastava et al. (Scheme 12.5c). The reaction... 

Treatment of polymer-bound methyl 2-acetylamino-3-(dimethylamino)prop-2-enoate 68 with excess 2-aminothiazole in a mixture of toluene, DMF, and acetic acid at 60°C (Scheme 32) yielded the corresponding thiazolo[3,2-a]pyrimidin-6-yl)acetamide 69 [57],... 

Huang X, Liu Z. Solid-phase synthesis of 4(lH)-quinolone and pyrimidine derivatives based on a new scaffold-polymer-bound cyclic malonic acid ester. J. Org. Chem. 2002 67 6731-6737. 

Scheme 9.10 Bis(pyrimidine)-based Pd-bound polymer 30 active in the Sonogashira reaction obtained by ring-opening metathesis polymerization (ROMP) of the norbornene 31 with the diene 32 and subsequent treatment with PdClj [110].

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