4- Azido-6- pyrimidines

Base-induced ring-opening of pyrimidines, or nitrene formation (as in the pyrolysis of azido-pyrimidines) can give imidazoles (see CHEC-I). There are also a few examples of photochemical ring contraction. For example, 4-heteroaryl substituted 1,4- (or 3,4-)dihydropyrimidines give some imidazole products (Equation (76)) <83RTC364>. 

Villalgordo et al. [22, 23] as well as Gayo and Suto [25] developed a strategy to cleave pyrimidines from the solid support. After oxidation of the thioether-linkage 17, aromatic substitution of the sulfonyl unit was performed with different N-nucleophiles as amines and azides to give free amino- or azido-pyrimidines 19 (Scheme 16.5). To demonstrate the stability of the linker, the resin-bound derivatives were subjected to different reactions such as saponification, ester reduction, acid chloride formation or Mitsunobu alkylation. A similar approach was presented later on by Hwang and Gong in the SPOS of 2-aminobenzoxazoles [26]. 

Pyrimidine, 5-arylazo-reduction, 3, 88 Pyrimidine, aryloxy-hydrolysis, 3, 91 Pyrimidine, arylthio-desulfurization, 3, 95 Pyrimidine, azido-reactions, 3, 82... 

Table 30.2. Assignment of the signals from 6-n-butyl tetrazoIo[1,5-a]pyrimidine (1) and 2-azido-5-n-...

Among other bicyclic amidine catalysts, 3,4,6,7,8,9-hexahydro-2//-pyrido[l,2-n]pyrimidine was also applied in the preparation of /3-alkoxy nitriles from Q ,/3-unsaturated nitriles and alcohols (99GEP 19803515). The azido group could be smoothly converted into a trifluoroacetylamido group by treatment with (Cp3CO)2 in the presence of Ph3P and 2,3-dihydro-2//-pyrido[l,2-n]pyrimidin-2-one under Ar in THE (99HCA2380). 

Thienopyrrolopyrimidines can be prepared by a photochemical reaction. Upon heating or irradiation of 4-azido-5-(2-thienyl)pyrimidine in trifluoroacetic acid solution, the tricyclic product is formed in good yield <1989CPB2933> (Equation 1). 

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

In a similar tandem reaction, ethyl 2-azido-l-methyl-l/7-indole3-carboxylate 364 is converted to indolo[3,2- ]l,2,3-triazolo[l,5- ]pyrimidin-5-ones 366 via triazole intermediates 365 that are not separated (Scheme 58). Products 366 are obtained in 80-90% yield as potential intercalates of DNA <2003H(60)2669>. 

Thus, 5-methoxypyrimidine 103 when treated with lithium tetramethylpiperidide (LTMP) and subsequently by tosyl azide led to formation of the 2-azido derivative 104, which spontaneously undergoes ring closure to 8-methoxytetrazolo[l,5-c]pyrimidine 105. 

Purine and pyrimidine nucleosides of AZT (Zidovudine, 3 -azido-3 -deoxythymidine) with [RuO ] (from RuClj/K S O/aq. M KOH) gave l-((3-azido-2,3-dideoxy-P-D-eryf/tro-pentafuranosyl-5-uronic acid)-thymine (Fig. 2.11) [335]. 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

On treatment with polyphosphoric acid, the pyridyltetrazole (101) furnished the 3-azido-4-oxo-4//-pyrido[l,2-a]pyrimidine (102) in 6° yield.166... 

Hydrazono-4-oxo-4ff-pyrido[l,2-u]pyrimidines were transformed by sodium nitrite in hydrochloric acid at 0-5 C to the corresponding 2-azido compound (102).166-287 2-Azido-4-oxo-4//-pyrido[l,2-azide-tetrazole tautomerism.290... 

As part of their study on aza-transfer reactions, Tisler and co-work-ers289 290 reacted 2-hydrazino-4-oxo-4//-pyrido[l,2-u]pyrimidine with various diazo derivatives and obtained 2-azido- and 2-amino-4-oxo-4/f-pyrido[l,2-u]pyrimidines. From 2-azido-4-oxo-4/f-pyrido[l,2-u]pyrimi-dines various derivatives of 2-(l,2,3-triazol-l-yl)-4-oxo-4//-pyrido[1.2- ]-pyrimidine (221) were prepared by reaction with acetylene,287 1,3-dioxo compounds,166 ordiethylamine.291 For further ring transformation reactions of the 2-azido-4-oxo-4//-pyrido[l,2- ]pyrimidine (102), see Section lll.C.lO. 

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