2- imidazo pyrimidine

The parent compound is a moderately weak base (pK 3.59), comparable with substituted aminopyrazines. The 2,3-dihydro compound 5, however, is very much stronger (pK 9.32). The base-weakening effect of the nitrogen in the 7-position is clearly demonstrated by comparison with the dihydroimidazopyridine (7). The latter compound has a pKa of 12.51 units. Similar effects are found in the imidazopyridazine and imidazo-pyrimidine series. No evidence has been found for covalent hydration in any of the triazaindenes studied. ... 

Imidazo[l,2-c]pyrimidine, 2,5,7-trichloro-nucleophilic displacement reactions, 5, 627 Imi dazo[ 1,2-a]pyrimidines pK, 3, 338 reactivity, 5, 627 synthesis, 5, 647 Imidazo[ 1,2-c]pyrimidines reactions, 5, 627 structure, 5, 610 synthesis, 5, 648-649 lmidazo[ 1,5-a]pyrimidines reactions, 5, 628 synthesis, 5, 649 lmidazo[l,5-6]pyrimidines synthesis, 5, 649-650 Imidazopyrrolopyridines bromination, 4, 506 lmidazo[4,5-6]quinoxaline nomenclature, 1, 22... 

Completely trivial names continue in use for good reasons, of which an important one is the need for a simple name for frequent communication concerning a commonly encountered compound or structure. For obscure compounds there is surely neither need nor desirability to perpetuate trivial names, and coining new trivial names is almost never justified. Let us, however, consider purine , the trivial name for what might more systematically be named imidazo[5,4-ring system is so important in biochemistry that exclusive use of one of the systematic names would be intolerable. If the name purine were not available, another short trivial name would inevitably be coined, or even an acronym ( IP or TAP ). It is better to retain the name sanctioned by roughly a century of use, and benefit from a link in comprehension with the past. 

The formal derivation of the analogs, described in the foregoing, represents, from the point of view of systematic organic chemistry, a shift to the derivatives of other heterocyclic systems. In the case of pyrimidine aza analogs we arc dealing with derivatives of symmetrical or asymmetrical triazine in the case of purine aza analogs, the derivatives produced are those of imidazo[4,5]-i -triazine and z -triazolo [4,5-d] pyrimidine. 

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

The tautomeric equilibrium in variously substituted imidazo- 53 (93KGS1353) and triazolo-fused pyrimidines 54 (88KGS1489 91KGS1539 93KGS1353 93KGS1357) has been comprehensively studied by Desenko and colleagues, whose results were summarized in a special review (95KGS147). 

Theoretical calculations have predicted that imidazo[l,2-a]pyrimidine (160) should be attacked at C-3 by electrophiles, although reactivity will be lower than in the corresponding imidazo[l,2-a]pyridines (see D,l,e) (74JHC1013). The 3-bromo derivative of 160 was formed when the parent was treated with NBS in chloroform (66JOC809). The usual transformation of oxo to chloro was responsible for the preparation of 5-chloroimidazo[ 1,2-a]pyrimidine [66LA(699) 127]. 

The isomeric imidazo[l,5-a]pyrimidine (161) gave the 1,3-dibromo derivative when exposed to bromine or NBS (72BSF2481). Iodination of benzimidazo[2,l- >]quinazolin-12(5 or 6//)-ones was accomplished by boiling them with bromine in the presence of sodium or potassium iodide. Substitution took place at the 9-position in the benzimidazo moiety (91MI3). 

Paudler and Helmick515 have measured half-lives for deuteration of some heterocycles by deuterated sulphuric acid at 100 °C. The equivalent first-order rate coefficients (lO ) are as follows imidazo[l, 2-a]pyridine, 427(3-H) imidazo[l,2-a]pyridine-N-methiodide, 62(3-H) imidazo[l,2-a]pyrimidine, 123-(3-H) imidazo[l,2-a]pyrimidine-N-methiodide, < 6.4 (3-H, 5-H) 1,2,4-tri-azolo [1,5-a]pyridimidine, 128(5-H) 1,2,4-triazolo [1,5-a]pyrimidine-N-methiodide, 11.7 (5-H). The lower reactivity in each case of the corresponding methiodides shows that the bases react as such and not as the conjugate acids. 

Kinetic studies of base-catalysed hydrogen exchange of heterocyclic compounds have been carried out. Paudler and Helmick515 measured second-order rate coefficients for deuteration of derivatives of imidazo[l,2-a]pyridine(XXXIII), imidazo[l,2-a]pyrimidine(XXXIV), and 1,2,4-triazolo[1,5-a]pyrimidine(XXXV)... 

Imidazo[l,2-c]thieno[3,2-e]pyrimidines were investigated as possible broncho dilatators. A facile microwave-assisted route for the synthesis of these tricyclic thieno derivatives was reported in quantitative yields via intermediate 4-chlorothieno[2,3-d]pyrimidines themselves synthesized under one-pot reaction conditions. The last step was performed for only 1 min... 

Almost accidentally, Bienayme and Bouzid discovered that heterocyclic amidines 9-76 as 2-amino-pyridines and 2-amino-pyrimidines can participate in an acid-catalyzed three-component reachon with aldehydes and isocyanides, providing 3-amino-imidazo[l,2-a]pyridines as well as the corresponding pyrimidines and related compounds 9-78 (Scheme 9.15) [55]. In this reachon, electron-rich or -poor (hetero)aromatic and even sterically hindered aliphatic aldehydes can be used with good results. A reasonable rahonale for the formation of 9-78 involves a non-con-certed [4+1] cycloaddition between the isocyanide and the intermediate iminium ion 9-77, followed by a [1,3] hydride shift. 

Reaction of pyrido[ 1,2- pyrazin-4-one 304 with methyl cyanoacetate, cyanamide, and JI-oxo nitriles in AcOH at 70 °C gave imidazo[ l,2- ] pyridine 331, imidazo[l,2- ]-pyrimidine 332, and tetracyclic heterocycles 333, respectively <1996JHC639>. 

The pyrimido[2,l+][l,3]oxazine 322 rearranged into the imidazo[l,2- ]pyrimidine 323 on heating in DMF in the presence of benzoic acid (Equation 35) <2000NN1381>. 

Pyrido[2, 3 4,5]imidazo[l,2- Pyrido[3, 2 4,5]imidazo[l,2-A]pyridazine <2004CC2466>... 

A microwave-assisted, one-pot, two-step protocol was developed for the construction of polysubstituted 2-aminoimidazoles 101 via the sequential formation of imidazo[l,2-a]pyrimidinium salts from readily available 2-aminopyrimidines 99 and a-bromocarbonyl compounds 100, followed by opening of the pyrimidine ring with hydrazine <06OL5781>. A... 

Aldehydes and the corresponding 2-aminopyridine, pyrazine, or pyrimidine are admixed in presence of a catalytic amount of clay (50 mg) to generate iminium intermediate. Isocyanides are subsequently added to the same container and the reactants are further exposed to MW to afford the corresponding imidazo[l,2-a]pyridines, imi-dazo[l,2-a]pyrazines and imidazo[l,2-a]pyrimidines (Scheme 6.48). The process is general for all the three components, e. g. aldehydes (aliphatic, aromatic and vinylic), isocyanides (aliphatic, aromatic and cyclic) and amines (2-aminopyridine, 2-amino-pyrazine and 2-aminopyrimidine). A library of imidazo[l,2-a]pyridines, imidazo[l,2-ajpyrazines and imidazo[l,2-a]pyrimidines can be readily obtained by varying the three components [151]. 

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