Pyrimidines Mercaptopyrimidines

A mixture of 2 g of 4,5-diamino-6-mercaptopyrimidine and 10 ml of 9B% formic acid was heated at 70°C for two hours and then evaporated to dryness on the steam bath to give as a residue, 7-amino-thiazolo (5,4-d) pyrimidine. 

The synthesis of 2-substituted pyrimidines from 1,3-dicarbonyl compounds and urea derivatives was first described by Evans2 and was later improved by Hunt, McOmie, and Sayer3 for the preparation of 2-mercapto-4,6-dimethylpyrimidine. Burness4 employed 3-ketobutyraldehyde acetal in this procedure to give 2-mercapto-4-methylpyrimidine. 2-Mercaptopyrimidine has been prepared from 1,1,3,3-tetraethoxypropane and thiourea by variations of this basic method 3 6 6 as well as by the reaction of 2-chloropyrimidine with thiourea 1 or sodium hydrosulfide.8... 

This preparation describes a convenient and general method of synthesis of substituted pyrimidines from compounds containing a /3-dicarbonyl group, either intact or as the corresponding ketal. The usefulness of the 2-mercaptopyrimidines is enhanced by the ease of removal of the mercapto group by desulfurization 9 or oxidation 10 and its replacement by other functional groups.1 ... 

The coordination abilities of A-heterocyclic thiols such as 2-thiopyridine, HSpy (66a), 2-mercapto-pyrimidine, Hspym (66b), or 2-mercaptothiazoline (67) with rhenium centers has already been described for oxorhenium(V) complexes is Section 5.3.2.3.L It has been outlined that ligands with five-membered rings preferably coordinate as monodentate neutral thiones whereas chelate formation is possible for mercaptopyridine or mercaptopyrimidine. Similar complex formation... 

Iron-nitrosyl complexes continue to attract attention. Complexes with mercaptopurines and mercaptopyrimidines have been examined by both NMR and ESR. (57) The mercapto group in mercaptopyrimidines is the preferred binding site for the Fe atom, provided that the pH value allows its ionization. At lower pH a pyrimidine nitrogen atom is the binding site. At biologically relevant pH values equilibrium between complexes of types I and III occurs [7]. In the... 

New types of acyclic nucleoside phosphonates (408-412) have been obtained using a multistep synthetic approach based on N-1, O- and S-alkylations of 4-and 2,4-substituted 6-hydroxy and 6-mercaptopyrimidines with diisopropyl 2-(chloroethoxy)methylphosphonate and (R) or (S) - [2-(diisopropylphos-phonyl)methoxy] propyl tosylate. Inhibitory activity against viruses of both the nucleoside phosphonates and the related phosphonic acids was investigated. It was found that the 6[2-(phosphonomethoxy)ethoxy]pyrimidines must bear an (unsubstituted) amino group concomitantly on both C-2 and C-4, or an amino on C-2 and an OH group on C-4, to display antiviral activity. Alkyl ethers are preferred over alkyl thioethers. The compounds of the 6-[2-(phos-phonomethoxy)ethoxy] and 6-[2-(phosphonomethoxy) propoxy]pyrimidine... 

The best preparative method for mercaptopyrimidines varies from position to position from thioureas and their equivalents. Thiones in any of the electrophilic positions are prepared by thiolysis of halo-pyrimidines, or commonly by thiation of pyrimidinones using phosphorus pentasulfide or, more recently, the superior Lawesson reagent 2,4-bis-/ -methoxyphenyl-l,3,2,4-dithiadiphosphetane 2,4-disulfide. Thiolysis in the 5-position requires a metal sulfide and a 5-bromide under vigorous conditions. Alternatively, pyrimidines substituted with strongly electron-donating substituents may be sulfonated, for example, by chlorosulfonic acid, in the 5-position with subsequent reduction to thiol. 

Bridgedhead thiazolo[3,2-a]pyrimidines, and their isosteres occupy a unique place in medicinal chemistry due to their wide application as drug and drug-intermediates [7-11]. Several methods are known for synthesis of thiazolo[3,2-a]pyrimidine derivatives, from 2-mercaptopyrimidines and a-halo ketones, and by cyclocondensation of a-aminothiazoles with P-diketones, P-keto aldehydes, and their acetals, P-chlorovinyl ketones and aldehydes. 

Difluorophenyl)methyl]thio -7- [(1 S,2S)-2-hydroxy-l-(hydroxymethyl)propyl] amino thiazolo [4,5 -d]pyrimidin-2(3H)-one 126 (Seheme 56) which are useful for treating a chemokine mediated diseases sueh as asthma, allergic rhinitis, COPD, inflammatory bowel disease, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis, cancer, etc., was prepared in a 7-step process, starting from 4-amino-6-hydroxy-2-mercaptopyrimidine and 2,3-difluorobenzyl bromide [82],... 

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