Pyridyl carboxylic acids

P,y-Unsaturated ketones7i-Allylnickel halides (4, 33) react with 2-pyridyl-carboxylic acid esters to form a mixture of p,y- and a,/i-unsaturatcd ketones in which the former isomer predominates (equation I). 2-Pyridylbenzoate can be used... 

Pharmaceuticals and Agrochemicals. Thioglycohc acid and its esters are useful as a raw material to obtain biologically active molecules. In cephalosporine syntheses, (4-pyridyl)thioacetic acid [10351 -19-8] (65) and trifluoromethane (ethyl) thioglycolate [75-92-9] (66) are used as intermediates. Methyl-3-ainino-2-thiophene carboxylate can be used as intermediate for herbicidal sulfonylureas (67) and various thiophenic stmctures (68). 

The reaction of 2-(a-pyridyl)alkylmalonic acid with J -piperideine leading to formation of 3-((x-pyridyl)quinolizidine-l-carboxylic acid on decarboxylation, has been used by Van Tamelen and Foltz (316) for the syntheis of the alkaloid lupanine (Scheme 20). A very elegant synthesis of matrine has been accomplished by Bohlmann et al. (317). 

Hydrolysis of ethyl 9-fluoro-10-(4-methylpiperazino)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate in a boiling mixture of AcOH and 35% HCl afforded 7 HCl (97USP5703233). That of (3S)-3-methyl-10-(2,6-dimethyl-4-pyridyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- e]-l,4-benzothiazine-6-carboxylate gave the 6-carboxylic acid (OOMIPIO). 7-Oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylic acid was obtained from its ethyl ester by alkalic hydrolysis in 20% yield (99AP19). 

Additional acceleration of acylation can be obtained by inclusion of cupric salts, which coordinate at the pyridine nitrogen. This modification is useful for the preparation of highly hindered esters.122 Pyridine-2-thiol esters can be prepared by reaction of the carboxylic acid with 2,2 -dipyridyl disulfide and triphenylphosphine123 or directly from the acid and 2-pyridyl thiochloroformate.124... 

Irreversible inhibition is probably due to the alkylation of a histidine residue.43 Chymotrypsin is selectively inactivated with no or poor inhibition of human leukocyte elastase (HLE) with a major difference the inactivation of HLE is transient.42,43 The calculated intrinsic reactivity of the coumarin derivatives, using a model of a nucleophilic reaction between the ligand and the methanol-water pair, indicates that the inhibitor potency cannot be explained solely by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack 43 Studies on pyridyl esters of 6-(chloromethyl)-2-oxo-2//-1 -benzopyran-3-carboxylic acid (5 and 6, Fig. 11.5) and related structures having various substituents at the 6-position (7, Fig. 11.5) revealed that compounds 5 and 6 are powerful inhibitors of human leukocyte elastase and a-chymotrypsin thrombin is inhibited in some cases whereas trypsin is not inhibited.21... 

The heterobifunctional PEGs are very useful in linking two entities in cases where a hydrophilic, flexible, and biocompatible spacer is needed. Preferred end groups for heterobifunctional PEGs are maleimides, vinyl sulfones, pyridyl disulfides, amines, carboxylic acids, and /V-hydroxysuccinimide (NHS) esters. 

The PBI molecules studied include pyridyl-(P-PBI), terpyridyl (TP-PBI), and thiol-terminated (T-PBI) perylene-3,4 9,10-tetra-carboxylic acid bisimides, that contain bulky ferf-butylphenoxy substituents at 1,6,7,12 bay positions, and pyridyl-(Py-PBI) and terpyridyl- (TPy-PBI) terminated perylene-3,4 9,10-tetra-carboxylic acid bisimides, that contain bulky pyrrolidinyl substituents at 1,7 bay positions (Fig. 26a) [327-329]. 

Amino-5-(pyridyl)thiophene-2-carboxylic acids (359) were reacted with diethyl methylenemalonate in DMF at 150°C for 2 hr to give N-[5-(pyridyl)thien-3-yl]aminomethylenemalonates (360) 61-62% yields [82-JAP(K) 116077],... 

The cyclization of diethyl iV-substituted N-(6-alkyl-2-pyridyl)amino-methylenemalonates (265, R2 = Et) in polyphosphoric acid at 200-230°C for 10 min gave 1-substituted 7-alkyl- 1,4-dihydro-1,8-naphthyridine-3-carboxylic acids (1022, R = Me, Et R1 = alkyl R2 = H) in 17-56% yields (71GEP2108046). From the mother liquor, 2-(substituted amino)-6-alkylpyridines could be recovered. 

Rosoxacin was obtained in 16% yield by the cyclization of isopropylidene N-ethyl-N-[3-(4-pyridinyl)phenyl]aminomethylenemalonate in pol-yphosphoric acid at 125-137°C for 30 min [77JAP(K)116460], Isopropylidene 2-pyridyl- and 2-quinolinylaminomethylenemalonates (1195) were cyclized in boiling phosphoryl chloride by the action of poly-phosphoric acid at I35-140°C. When the formation of hydrogen chloride gas ceased, the reaction mixtures were treated with an alcohol or water to afford the corresponding alkyl 4-oxopyrido[ 1,2-a]pyrimidine-3-carbox-ylates or alkyl 1 -oxopyrimido[ 1,2- ]quinoline-2-carboxylates (1196, R2 = alkyl) in 51-96% yields or to afford carboxylic acids (1196, R2 = H) in 64-84% yields (79MIP2 80MIP3 84S152). 

Diethyl mercapto[(2-pyridyl)amino]methylenemalonate (1724) was treated with methylene iodide in DMF in the presence of potassium carbonate at 50-60°C for 6 hr to give 3-(2-pyridyl)-l,3-thiazetidin-2-ylidene malonate (1725) (89EUP312794). Thiazetidinylidenemalonate ( 1725) was cyclized in fuming sulfuric acid at 0°C for 12 hr to give 4-oxo-l,3-thiazeto[3,2-u]-l,8-naphthyridine-3-carboxylic acid (1726) in 61% yield. 

The (E)-alkene (74) is formed from Wittig reaction of the corresponding phenyl 3-pyridyl ketone the stereochemical preference is determined by an interaction (either hydrogen bonding or salt bridging) between the carboxylic acid chain being introduced and the amide tether provided by the reactant." ... 

The emission from [Ru(bpz)3] is quenched by carboxylic acids the observed rate constants for the process can be rationalized in terms of the protonation of the non-coordinated N atoms on the bpz ligands. The effects of concentration of carboxylate ion on the absorption and emission intensity of [Ru(bpz)3] have been examined. The absorption spectrum of [Ru(bpz)(bpy)2] " shows a strong dependence on [H+] because of protonation of the free N sites the protonated species exhibits no emission. Phosphorescence is partly quenched by HsO" " even in solutions where [H+] is so low that protonation is not evidenced from the absorption spectrum. The lifetime of the excited state of the nonemissive [Ru(Hbpz)(bpy)2] " is 1.1ns, much shorter than that of [Ru(bpz)(bpy)2] (88 nm). The effects of complex formation between [Ru(bpz)(bpy)2] and Ag on electronic spectroscopic properties have also been studied. Like bpz, coordinated 2,2 -bipyrimidine and 2-(2 -pyridyl)pyrimidine also have the... 

It may be suspected that the genuinely topotactic (as secured by the molecular precision of the AFM [18]) photodimerization of 2-benzyl-5-benzyli-denecyclopentanone [118] might be a good candidate for a quantitative preparative photo dimerization to give the head-to-tail anti-[2+2] dimer. Early quantitative solid-state [2-1-2] photodimerizations (most of the published mechanistic interpretations of which can no longer be accepted) are listed in [110]. These deal with the anti dimerization of acenaphthylene-1,2-dicarboxylic anhydride, the head-to-head syn dimerization of acenaphthylene-1-carboxylic acid, the syn dimerization of 5,6-dichloroacenaphthylene, and the thermally reversible head-to-tail anti dimerization of seven ( )-2,6-di-f-butyl-4-(2-aryl-ethenyl)pyrylium-trifluoromethanesulfonates. All of these reactions proceed fully specific. On the other hand, quantitative photoconversions of a 1 1 mixed crystal of ethyl and propyl a-cyano-4-[2-(4-pyridyl)ethenyl]cinnamates gives mixtures of diesters with one (A>410 nm) or two cyclobutane rings (no cutoff filter). 

A number of syntheses of substituted 2,3 -bipyridines are worthy of note. Tetracyclone heated at 215°C with nicotinonitrile affords 3,4,5,6-tetraphenyl-2,3 -bipyridine, whereas 3,4-di(2-pyridyl)pyridine is obtained by an oxidative degradation of the corresponding 6,7-disubstituted thiazolo[3,2-a]-pyridinium salt. Nicotinic acid on UV irradiation in aqueous solution at pH 4-6 gives 2,3 -bipyridine-5-carboxylic acid, whereas irradiation of picolinic acid in the same pH range in the absence of metal ions gives some 2,3 -bipyridine. 6,6 -Diphenyl-2,3 -bipyridine is thought to be formed from... 

Inhibitors of the blood clotting factor thrombin would in principle prove useful in preventing inappropriate clot formation that potentially leads to stroke and heart attack. Reaction of the carboxylic acid (56-2) with thionyl chloride leads to the corresponding acid chloride (56-3). Treatment of that intermediate with the substituted pyridyl amine (56-1) leads to the amide (56-4). Catalytic hydrogenation of (56-4) reduces the nitro group to the primary amine (56-5). Condensation of that ortho-diamine with the carboxyhc acid (56-6) in the presence of carbonyl diimidazole... 

Diaryl ketones.2 In the presence of this complex (1 equivalent) S-(2-pyridyl) aryl thioates (1 equivalent), prepared from aryl carboxylic acids, undergo reductive homocoupling to diaryl ketones (equation I). 

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