6-Bromo-2- imidazo pyridine

Imidazo[l,2-n]pyridine, 8-amino-synthesis, 5, 631 Imidazo[l,2-n]pyridine, 3-aryl-synthesis, 5, 631-632 Imidazo[l,2-n]pyridine, 3-bromo-synthesis, 5, 631... 

Imidazo[4,5-c]pyridine, 6-amino-4-bromo-reactions, 5, 621 synthesis, 5, 641... 

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. 

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]. 

In order to assemble the imidazo[l,2-a]pyridine scaffold, 2-amino-3-chloropyridine was reacted with 2-bromo-p-fluoroacetophenone <03OL1369>. The product was transformed in five steps to a desired antiviral template. 

Reaction of imidazo[4,5-fc]pyridine (97), but not its 5-amino derivative, with perphthalic acid (49JA1885) or hydrogen peroxide in acetic acid (66UC403) gave the A( -oxide (98). Peracetic acid was used to prepare the A7 -oxides of 6-bromo-, 6-chloro, 6-bromo-5- and -7-methyl-, and 5,7-dimethyl-imidazo[4,5-fc]pyridine (98) (59JOC1455). The N-oxides can be catalytically reduced to (97) (80JHC17S7). 

The ring synthesis of imidazo[l,2-a]pyridines is based on the Chichibabin route to indolizines (Section 25.1.2), but using 2-aminopyridines instead of 2-alkylpyridines. The initial reaction with the halo-ketone is regioselective for the ring nitrogen, so isomerically pure products are obtained. 2-Oxoimidazo[l,2-a]pyridines are the products when an o-bromo-ester is used instead of a ketone. 

Spiro[cyclohexane-l,2 -(3 H)-l//-imidazo[4,5-b]pyridine] 5-bromo derivative 645 reacts similarly with manganese(IV) oxide in tbe presence of a nucleopbile. Tbe oxidation of this substance led to tbe formation of intermediate 646 wbicb perhaps then underwent debydrobromination in tbe presence of morpholine and gave intermediate dehydropyridine 647 with a 6,7-triple bond in the ring. The final base 648 formed as a result of addition of the second nucleophilic molecule across the 6,7-triple bond (94HCA2175). 

Scheme 58 Ci nc-Substitution in 6-bromo-2-(4-fluorophenyl)imidazo[ 1,2-a]pyridine by action of NH-azoles...

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