Imidazo pyridine ring

BZl and BZ2 (a2, a 3, and a5) sites. A two-dimensional NMR analysis (409) found that Zolpidem possessed only one family of conformations, in which the acetamide moiety was positioned 2 A above the plane of the imidazo-pyridine ring. This is consistent with the crystal structure of edpidem (399). Saripidem also exists in this conformation, which is presumed to impart BZl affinity. However, saripidem m exist in a second conformation in which the acetamide group is in the plane of the imi-dazopyridine system, and this conformation m confer BZ2 affinity. 

Fig. 13.2. Illustration of the basic concept of Basis Products, (a) The PGVL reaction scheme of VRXN-2-00051 (formation of the H-imidazo[1,2-a]pyridine ring system using aminoheterocycles and alpha-halo ketones) is used for the illustration (b) The Basis Products of A are formed by all A reactants with one constant reactant (B CAP, 1 -bromopropan-2-one). The Basis products of are formed by all reactants with a constant A reactant (A CAP, 2-amino pyridine). The blue triangle and yellow hexagon represent two such basis products. The red star represents a product molecule which is related to those two corresponding basis products.

Imidazo[4,5-b pyridines. Methyl chloride reacts with 78 at the nitrogen atom of the pyridine ring, but with 79 at the unsubstituted imidazole nitrogen atom.183 The Former result is surprising because it does not fit a prediction based on a consideration of the relative reactivities of pyridine and 1-methylimidazole.44... 

Proton NMR and carbon-13 NMR studies have been carried out to establish whether methoxy substitution in the pyridine ring of a series of 2-(2-methoxyphenyl)imidazo[4,5-/ ]pyridines (92) and related 2-(2-methoxyphenyl)imidazo[4,5-c]pyridines alters the major site of protonation from the pyridine ring to the imidazole ring <87AX(C)1937>. By comparing the 13C chemical shifts for the carbon atoms in the pyridine ring in both the free base and the corresponding hydrochloride salts,... 

A derivative of the almost fully reduced imidazo[4,5-c]pyridine ring system, 3,3a,4,5,6,7-hexa-hydro-2//-imidazo[4,5-c]pyridine (357) has been prepared (Equation (29)) <88IZV409>. Cyclization of l-hydroxy-3-hydroxyamino-2,2,6,6-tetramethyl-4-piperidone oxime acetate (356) with benz-aldehyde or formalin at — 20°C for 3 d gave the reduced bicyclic compound (357). 

There is little published work on the catalytic hydrogenation of the imidazo[l,2-fl]pyridines (63), but what there is indicates that reduction of the pyridine ring takes place preferentially to give the 5,6,7,8-tetrahydro derivatives (64) (77HC(30-2)117, 73JMC1272). 

The reactions of groups attached to the imidazo[l,2-a]pyridine ring are unremarkable... 

The imidazo[l,5-a]pyridine ring system has been successfully functionalized with various electrophilic reagents, metalated, and reduced in one case. No nucleophilic displacements of leaving groups have been reported on appropriate derivatives. 

Oxidation at N-4 (141) of the imidazo[4,5-c]pyridine ring system (140) has been accomplished with hydrogen peroxide in acetic acid and with perphthalic acid (64JOC2611,80JHC1757, 64CPB866). 

There has been one report of the synthesis of the imidazo[l,2-a]pyridine ring system (336) by the closure of both rings by the reaction of (334) and (335), but closure of the pyridine ring probably occurs first (73ZOR2006). 

By a similar strategy, an imidazopyridine scaffold 32 was synthesized by reaction of pentafluoropyridine and benzamidine 31 [56] and, in this case, subsequent nucleophilic substitution occurs at the 5 position to give 33, presumably because of interaction of the nucleophile and the imidazo ring NH bond which directs the incoming nucleophile to the less activated site adjacent to pyridine ring nitrogen. 

The first report of the synthesis of an imidazo[4,S-6]pyridin-S--one by closure of a pyridine ring is a base-catalysed cyclization of the amino-malonylidene diester. Complementary to this method is that in which a monoester mononitrile of malonic acid is heated in acetic acid to give a high yield of the fused pyridinone. Me... 

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