Imidazole ring construction

The imidazole ring can be constructed on the quinoline by reaction with bromomethyl phenacyl hydrazones to afford 493 (91H2373). On the other... 

Construction of the imidazole ring onto a triazine has been also used for the synthesis of this group of compounds. The reaction of 3-aminobenzofl, 2,4]triazine with a-bromoacetaldehyde acetal gave the [1,2-b] linear isomer. On the other hand, the similar reaction on 1-oxide 461... 

An intramolecular heteroaryl Heck was the pivotal step in the synthesis of 5-butyl-1-methyl-l//-imidazo[4,5-c]quinolin-4(5//)-one (63), a potent antiasthmatic agent [46], The optimum yield was obtained under Jeffery s ligand-free conditions, echoing Ohta s observation for the intermolecular version. Once again, the Caryi—Caryi bond was constructed at the C(5) position of the imidazole ring. Another intramolecular heteroaryl Heck cyclization of pyrrole and imidazole derivatives was also reported to assemble annulated isoindoles [47]. 

A benzofuran ring replaces one of the benzene rings of the biphenyl moiety present in many of the sartans in the rather more complex drug saprisartan (80-10). It is of note, further, that the acidic proton is provided in this case by a trifluorosulfo-namide instead of the more common tetrazole ring. Construction of the imidazole fragment begins by nitrosation of the (3-ketoester (79-1) by means of sodium nitrite in acid to afford the oxime (79-2). Reaction with acetyl chloride leads to the ester (79-3). Reaction of this last intermediate with the iminoether from propionitrile then affords the imidazole (79-4). 

The thioamide function also provides the entry for the construction of a fused imidazole ring, though the sequence is somewhat more complex due to the need to form a new carbon-carbon bond. Reaction of the thioamide (18-1) with methylamine proceeds to give the corresponding amidine this is transformed into a good leaving group by conversion to the A-nitroso derivative (18-2) by treatment with nitrous... 

Several solid-phase approaches to afford purines were performed. Some may involve selective substitution of the purine directly others begin by construction of a pyrimidine scaffold followed by closure of the imidazole ring. 

The pseudoreceptor model was constructed with six amino acid residues. The imidazole ring of the ligands and the terminal basic function were saturated via... 

Bellemin-Laponnaz and coworkers use a different route [67]. They construct the oxazoline ring on the imidazole ring using valinol to introduce a second chiral centre (see Figure 6.28). 

An unprecedented attack on an azide group by an iminium species, generated in situ under Vilsmeier conditions, furnishes a novel route to construct the imidazole ring. Thus, A -aryl-5-chloro-2-(dimethylamino)imidazole-4-carbox-aldehydes 1257 were obtained from the Vilsmeier cyclization of A -aryl-2-azidoacetamides 1256. The possible mechanism for the reaction is illustrated in Scheme 316 <1998JOC7136>. 

Three more steps complete ring construction (Figure 25.7). Furnaratc, an intermediate in the citric acid cycle, is eliminated, leaving the nitrogen atom from aspartate joined to the imidazole ring. The use of aspartate as an... 

When an amino group is in a peri position with respect to the heteroatom [as in (54 after reduction)], an imidazole ring may be built to join the two by reaction with a carboxylic acid and PPE [2SI3]. Replacing the carboxylic acid by urea in the cyclization of (54.5) leads to the formation of a doubly fused imidazol-2-one ring [2513]. An imidazol-4-one may be constructed by the reaction of cither phenylglyoxal [3039, 3188] or the phenylazo derivative of chloroacetyl chloride [2366] with a 2-aminoazine. 

Considerable parallelism emerges from an examination of the major methods for the construction of oxazole, thiazole and imidazole ring systems. 

Oxidation of cyclic enol ether 35 with dimethyl dioxirane (DMDO) followed by in situ reduction of the intermediate epoxide with DIBALH gave secondary alcohol as a 10 1 mixture of diastereom-ers. Oxidation of these alcohols with TPAP/NMO afforded a 10 1 mixture of ketone 37 and its C16 epimer. The isomers were separated and the minor isomer was recycled to a 4 1 mixture of isomers by treatment with imidazole. Subsequent construction of the D-ring was performed by radical reduction of mixed thioacetal in the same way as that adopted by the Sasaki group, leading to octacycle 38. Stereoselective installation of the triene side chain was then carried out via (Z)-vinyl iodide 39... 

Figure 23 Association of a tetrahedraUy coordinated Cu(II) ion to four imidazolates to construct SOD zeolitic framework, four- and six-member ring windows to the zeolite sod-cage are shown.Cu (green), N (blue), and C (gray).

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