4- Amino-3-cyanopyridine

Alkylpyrido[2,3-,7jpyrimidine derivatives 344 were synthesized in three steps from 2-amino-3-cyanopyridine intermediates 341 by heating with HC(OEt)3 to produce the iminoether 342 followed by stirring with aqueous NH3 to give the amidine 343 which was then thermally cyclized to produce 344 (Scheme 11) <2001BML83>. 

The reaction products of the treatment of a, 3-unsaturated ketones with malononitrile in most cases are the expected derivatives of 2-amino-3-cyanopyridine. But an alternate direction with the formation of carbocyclic compounds 120 was described [128]. It is clear from structure 120 that two molecules of unsaturated ketone 5 and 1 equiv of malononitrile 107 are involved in the reaction (Scheme 3.37). 

Alkaline dimerization of o-aminonitriles is exemplified by the compound (82) formed by heating 2-amino-3-cyanopyridine in aqueous ammonia.33... 

The octahydroquinolines 24 and decahydroacridines were obtained from dimedone. On montmorillonite KSF clay, acridine derivatives 25 were obtained. Reaction of arylidenemalononitriles with cyclic ketones gave 2-amino-3-cyanopyridines 26. Reaction of diphenylamine and dicarboxylic acids or arylacetic acids was catalyzed by zinc chloride to give acridines. Pyrimido[4,5-Z>]quinolines 27 were synthesized. ... 

Nitriles can also be substituted for formamide. Benzonitrile and 2-aminobenzonitrile, autoclaved at 200°C, gave a moderate yield of 4-amino-2-phenylquinazoline (see 1). This reaction resembles, and is competitive with, the dimerization of aminonitriles discussed above it also proceeds by a similar mechanism. Other examples are the condensation of 3-cyanopyridine with 2-amino-3-cyanopyridine to give 2-(3-pyridyl)-4-aminopyrido[2,3-d]-pyrimidine (see 3) and of 5-cyano-l-methyl-4-aminoimidazole (see 18) with... 

Derivatives of 2-amino-3-cyanopyridines 154 have been synthesized from the reaction of arylidenemalononitriles 59 with a-methylene ketones in the presenee of ammonium aeetate and traces of solvent under both classical heating for 5 h in... 

A simple and efficient synthesis of 2-amino-3-cyanopyridines 326 was carried out through the reaction of arylidenemalononitriles 59 with cyclic ketones 325. The reaction under MWI in the presence of ACONH4, without or with a trace of solvent, gave 326 in 42 78% yields within 3.5-4.5min (Scheme 66), while the synthesis required 5.5-6 h, in refluxing benzene, to give lower yields (46-55%) (98JCR(S)330). 

In 2014, Odom and coworkers reported a titanium-catalyzed synthesis of 2-amino-3-cyanopyridines (Scheme 3.41) [89]. The reactions were performed in a one-pot manner with two manipulation steps. Firstly, titanium-catalyzed alkyne iminoamination and generation tautomers of 1,3-diimines. Then, 2-amino-3-cyanopyridines were formed in good to modest yields after treatment with base (DBU) and malononitrile. A Dimroth rearrangement mechanism for 2-aminopyridine formation was proposed based on the isolation of a 2-imino-l,2-dihydropyridine intermediate which undergoes rearrangement under the reaction conditions. 

Full details have been published of the synthesis of pyridines derived from the 1,5-dicarbonyl compounds resulting from the reaction of -ketoketene dithioacetals with the carbanions obtained by deprotonation of methyl ketones. 5 There have been two reports of the synthesis of pyridines from enamines and malononitrile.26,27 This route is exemplified by the conversion of the readily available enamines (10 Z=0 or S) into the 2-amino-3-cyanopyridines (11) ... 

---