Quinoline-3-carboxylic ester

Cycloaddition. Aldimines and those prepared in situ combine with ethyl propynoate readily. On applying the reaction to arylamines several quinoline-3-carboxylic esters have been prepared.The formation of l,4-dihydropyridine-3,5-dicarboxylic esters involves electrocyclic opening of the 1 1-cycloadducts and a Diels-Alder reaction. 

Gabriele et al. reported a transition-metal-catalyzed pyridine ring formation in 2007 [95]. Substituted quinolines 196 were synthesized efficiently by copper-catalyzed 6-endo-dig cyclization and dehydration of alkynylanilines 195 (Scheme 19.50). The reaction of silylated alkynes (R" = TMS) can also be catalyzed by Pdl2/KI to give quinolines 196a by a cyclodehydration-desilylation sequence. When the palladium-catalyzed reaction was carried out in the presence of CO and MeOH under oxidative conditions, the alkynes 195 were converted selectively into quinoline-3-carboxylic esters 197 in good yields. Quite interestingly, under nonoxidative... 

An example for Uquid phase chemistry with solid phase woikup has recently been published. In this case, a quinoline-carboxylic ester was transesterifled with an appropriate bromobenzyl alcohol. The Suzuki coupling with a boronic acid derivative proceeded smoothly and the quinoline handle was cleaved off. The advantage of this method lies in the ease of purification since the quinoline could be sequestered from the reaction mixture by protonation with sulfuric acid and recrystallization. - ... 

Finally, the quinoline ring can be methylated at the 3 position with retention of biologic activity. The starting quinoline is prepared by the same scheme as that used for the desmethyl compound by substituting the methylated oxosuccinate ester, S6, in the sequence. The initial quinoline carboxylate (87) is taken on to the dichloro compound (88) by the standard reactions. Condensation with the ubiquitous diamine (76) affords sontoquine (89)... 

C23H,i,FN04 124863-78-1) see Cerivastatin sodium diethyl 1,1 -(dithiodi-2,1 -elhanediyl)bis[6,8-difiuoro-l, 4-dihydro-7-(4-methyl-l-piperazinyl)-4-oxo-3-quinoline-carboxylic acid diethyl ester]... 

In the case of phosphoryl chloride, the primary products were 4-chloro-quinoline-3-carboxylates. As the quinoline-3-esters were very insoluble, the reaction products were hydrolyzed to quinoline-3-carboxylic acids, and the isomeric ratios were determined by H-NMR in trifluoroacetic acid. Thermal cyclization in Dowtherm A resulted mainly in formation of the 7-substituted isomer. In the case of chloro derivatives (250), only traces of 5-isomer could be detected. [Earlier, others observed and reported the formation of a small amount of the 5-isomer too (e.g., 46JA1204 47JA374]. 

Figure 4.22 demonstrates related base effects towards an a-bromo carboxylic ester, with the regioselectivities being almost perfect as compared to the ones in Figures 4.21. Quinoline eliminates HBr from a-bromo isovaleric acid ester with Saytzeff selectivity. In contrast, KO-tert-Bu effects Hofmann-selective HBr elimination. The selectivity of the ferf-BuO reaction... 

Radical nucleophile oxidation based on one-electron oxidation, known as the Minisci reaction, is employed for the functionalization of /V-heterocycles with acidic hydrogen peroxide in the presence of iron(II) salts (Figure 3.112).472 A range of A-heterocycles (pyridines, pyrazines, quinolines, etc.) which are activated towards attack by nucleophilic radicals when protonated are suited to this chemistry. The Minisci reaction is suitable for the preparation of carboxylic amides (from formamide), carboxylic esters (from pyruvic esters via a hydroxyhydroperoxide), aldehydes (from 1,3,5-trioxane) and alkylated pyridines (either from carboxylic acids or from alkyl iodides in dimethyl sulfoxide).473 The latter reaction uses dimethyl sulfoxide as the source of methyl radical (Figure 3.112). 

Irradiation of diazo quinoline 153 in alcohol provided the corresponding indole-3-carboxylic esters in 8-61% yield. Mechanistically, the transformation is a Wolff rearrangement and involves the formation of an intermediate carbene, ring contraction to ketene, and its solvolysis (76S754). 

The Mannich reaction of ketene 0,5-acetals can give rise to 3-lactams. Reaction with enol esters proceeds reasonably well, and that involving ArNH2, ethyl glyoxylate and vinyl acetate gives quinoline-2-carboxylic esters. ... 

The acrylates synthesized from acrylate 174 and semicarbazide 178 are boiled in benzene or toluene for l-2h this gives 2R-9, 10-difluoro-7-oxo-7//-l,3,4-thiadiazino[6.5.4-/,/]quinoline-6-carboxylic esters 180 (yields 40-60%) (98MC131, 99ZOR1447, 99ZOR1729, 01ZOR604) (Scheme 162). 

Oxazoles and 4,5-dihydrooxazoles can be transformed into quinolines. For instance, 5-(o-acylamino-aryl)oxazole-4-carboxylic esters 104, made from benzoxazinones 103 and isocyanoacetic ester, are converted into 3-aminO 4-hydroxy-2-quinolones 105 in an acid medium [109]. 

As for quinolines, isoquinoline derivatives can be prepared by ring transformation of other heterocycles. For instance, oxazole-4-carboxylic ester 74, obtained from phthalic anhydride and isocyanoacetic ester, is converted into the l-isoquinolone-3-carboxylic ester 75 in an acidic medium, probably by hydrolysis to the enaminocarboxylic acid 76 followed by cyclization. 

Reductions of aromatic nitro compounds provide a simple and general access to various heterocyclic compounds through the domino process (Scheme 9.23). Quinolines are important skeletal moieties present in various natural products and biologically active compounds [58]. Most common methods of their preparation involve condensation of o-amino benzaldehydes with an enolizable carbonyl compound (Friedlander synthesis) [59]. Miller et al. [60] reported an efficient synthesis of quinolines 109, in which a reduction of o-nitroaryl carbaldehyde by SnCl2 followed by condensation with an enolizable carbonyl compound in the presence of ZnCl2 yielded 109 through a domino process. In 2001, Bunce et al. [61] reported a domino nitroarene reduction/reductive amination sequence for the preparation of tetrahydroquinoline-4-carboxylic ester 110 with excellent yields. 

The preparation of thieno[3,2-fc]thiophene was reported by Iddon and co-workers [76, 77] and it is readily prepared in four steps from commercially available 3-bromothiophene (Scheme 17.1). Thus 3-bromo-thiophene can be lithiated in the 2-position with a bulky non-nucleophilic base such as lithium diisopropylamine. Quenching of the resulting thiophene anion with dimethylfonnamide or tV-formylpiperidine afforded the thiophene aldehyde. Treatment of this o-bromoaldehyde with ethyl 2-sulfanylacetate in the presence of base afforded thieno[3,2-fc]thiophene carboxylate ester in good yield. Hydrolysis of the ester group, followed by thermal decarboxylation of the resulting acid with quinoline in the presence of copper, afforded the unsubstituted thieno[3,2-f>]thiophene in overall yields of approximately 60 % over the four steps. 

---