Cyano-pyridine synthesis

A third synthesis which has resulted in the preparation of rieinine and a number of its derivatives is due to Schroeter, Seidler, Sulzbacher and Kanitz,i2 who foimd that cyanoacetyl chloride polymerises spontaneously to 6-chloro-2 4-dihydroxy-3-cyano-pyridine. The di-sodium derivative of this with methyl sulphate produces A -methyl-6-chloro-4-hydroxy-3-cyano-2-pyridone (6-chlororicininic acid), the mono-sodium derivative of which, with methyl bromide or sulphate, is converted into 6-chlororicinine and the latter is reduced by zinc and sulphuric acid to rieinine. A fourth synthesis, starting from 3-nitro-4-pyridone, is due to Reitmann. ... 

A safer, scaleable synthesis of 5-(2-cyano-pyridin-2-yloxy)-benz[l,2,5]oxadiazole 347 has been reported (Scheme 87) <20030PD1043>. 

The synthesis of isosophoramine (26) employs as crucial stages the partial hydrogenation of iV-alkyl salts of ) -acyl (or cyano) pyridines, and acid-catalysed cyclization of the resulting l-alkyl-3-acyl (or cyano)-2-piperideines. Alkylation of nicotinonitrile with 6-bromohexan-2-one ethylene ketal afforded the salt (27), which on palladium-catalysed hydrogenation yielded the piperideine (28). Anhydrous acid-catalysed (TsOH) cyclization of (28) gave the three quinolizidine stereoisomers (29)—(31), which were separated and analysed by n.m.r. spectroscopy and equilibration studies in acid (TsOH-CgH ) and alkaline (KOBu -Bu OH)... 

When the iV-alkoxypyridinyl compound is subjected to cyanide, it imdergoes the Reissert-Henze reaction to afford the 2-cyano-derivative with loss of the alkoxy group. Ethylation of W-oxide 311 with diethylsulfate afforded intermediate 312, which was treated with cyanide to afford the corresponding cyano-pyridine 313, an intermediate used in the synthesis of 5-adenosylmethionine decarboxylase inhibitor 314. ... 

Honda M, Tamura M, Nakao K, Suzuki K, Nakagawa Y, Tranishige K (2014) Direct cyclic carbonate synthesis from CO2 and diol over carboxylatimi/hydration cascade catalyst CeOa with 2-cyano-pyridine. ACS Catal 4 1893-1896... 

In this manuscript we disclose new synthetic methodology to prepare a member of a class of tetrasubstituted imidazole p38 inhibitors. The optimal route involves a thiazolium catalyzed cross acyloin-type condensation of a pyridinealdehyde with an iV-acylimine. The pyridinealdehyde was prepared in 3 steps and 68% yield from 2-chloro-4-cyano pyridine. The tosylamide precursor to the iV-acyl imine was prepared in two steps and 93% yield from isonipecotic acid. We have demonstrated the scope and some preliminary mechanistic studies concerning this new reaction. The resulting a-keto-amide is then cyclized with methyl ammonium acetate to provide the desired tetrasubstituted imidazole. Cbz deprotection and formation of a pharmaceutically acceptable salt completes the synthesis in 6 steps and 38% overall yield. 

The synthesis of this library began with the preparation of either 4- or 5-alko)y-2-cyano pyridines in parallel. While the access to 4-alkoxy derivative was easily accomplished via adulation of 5-hydroxy-2-cyano pyridine using a polymer bound base/ preparation of the 4-alko>y derivatives required the... 

The presence of a cyano group seems to be important[649]. The reaction has been successfully applied to halides of pyridine, quinoline, isoquinoline, and oxazoles[650]. An interesting application is the synthesis of tetracyanoquino-dimethane (789) by the reaction of / -diiodobenzene with malononitrile[65l]. 

Vinylpyridine (23) came into prominence around 1950 as a component of latex. Butadiene and styrene monomers were used with (23) to make a terpolymer that bonded fabric cords to the mbber matrix of automobile tires (25). More recendy, the abiUty of (23) to act as a Michael acceptor has been exploited in a synthesis of 4-dimethylaminopyridine (DMAP) (24) (26). The sequence consists of a Michael addition of (23) to 4-cyanopyridine (15), replacement of the 4-cyano substituent by dimethylamine (taking advantage of the activation of the cyano group by quatemization of the pyridine ring), and base-cataly2ed dequatemization (retro Michael addition). 4-r)imethyl aminopyri dine is one of the most effective acylation catalysts known (27). 

Pyridine, 6-cyano-l,2-dihydro-thermal dimerization, 2, 370 Pyridine, 2-cyanomethyl-tautomerism, 2, 159 Pyridine, 4-cyanomethyl-tautomerism, 2, 159 Pyridine, 2-cyano-2,3,4,5-tetrahydro-metallation, 2, 387 Pyridine, 2,5-diacetyl-ipso substitution, 2, 301 Pyridine, 3,5-diacetyl-l,4-dihydro-Hantzsch synthesis, 2, 482 Pyridine, 4-dialkylamino-as acylation catalysts, 2, 34 Pyridine, 2,2-dialkyl-l,2-dihydro-... 

Pyridin-2-one, 4-amino-3-cyano-synthesis, 2, 460 Pyridin-2-one, aroyl-synthesis... 

Pyridin-2-one, 4-cyano-l-methyl-Diels-Alder reaction, 2, 307 Pyridin-2-one, 3-cyano-5-nitro-synthesis, 2, 461... 

Pyridin-3-one, 3-cyano-6-hydroxy-4-methyl-azo dyes from, 1, 331 Pyridin-4-one, 2-amino-synthesis... 

X-ray crystallography, 3, 623 Ruscodibenzofuran synthesis, 4, 698, 709 Ruthenacyclobutane, 3-cyano-synthesis, 1, 667 Ruthenium complexes with pyridines, 2, 124 triazenido, 5, 675 Rutin... 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

To carry out the similar MCR involving 5-amino-3-methyl-l-phenylpyrazole, aromatic aldehydes, and 3-cyanoacetyl indoles, Zhu et al. [70] used microwave-assisted synthesis in glygol at 150°C. Application of other solvents was less effective and gave either no reaction products (water medium) or led to the sufficient yield decreasing (EtOH, HOAc, DME). Microwave irradiation was also used by Quiroga et al. [71] to synthesize ether 4-aryl-5-cyano-6-phenylpyrazolo[3,4-b]pyridine-3-ones or their dihydroderivatives under argone atmosphere. 

Enamines or imines can form pyridines by cyclization to a nitrile group, as shown in the production of compound (48). Alternatively, the nitrogen atpm of the nitrile can be made more nucleophilic by attack on the carbon atom by an external nucleophile. Ammonia causes cyclization of the dienamines (53) (77JHC1077) and (54) (78JAP(K)786878l) in both cases, elimination of the amine introduces the extra double bond. Dimethylamine or piperidine cause cyclization of l-cyano-2,5,5-trimethylhex-l-en-3-yne to the f-butyl-pyridine (55). There are a few other examples of the synthesis of bicyclic compounds from... 

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