2- amino-4-cyano-amide

Surprisingly, detailed analysis of several NMR spectra of isolated and purified compounds and a crystal structure analysis revealed the formation of 2-amino-4-cyano-amides. This reaction is the first case in which the oxygen for the newly formed amide bond emerges not from the solvent (H2O) but rather from the amide bond of a reactant. Also noteworthy is the concomitant nitrile formation from the primary amide, which does not normally occur under such mild conditions. Typical examples and their yields are given in Scheme 3.9. 

A more direct route involves the treatment of a-amino-cyano-amide with a protected formamidimide. The reaction is reported to take place at ambient temperature and provide good yields of the 1,4,5-tri-substituted and more appropriately functionalized imidazole, which is subsequently transformed into temozolomide. ... 

Silanes with functional groups like amino, cyano, flonr, phenyl, etc. are available commercially. The introduction of other functional gronps in the bonded moiety can be accomplished in two ways The silane with the functional gronp is prepared in sitn. To prepare a silane with an amide group, tri-alkoxy-3-aminopropyl silane is reacted with an acid chloride (C8 or C18). The thns prepared amide... 

Unsaturation may need to be determined, as well as functional groups such as hydroxy, carbonyl, carboxyl, alkyl, aryl, alkoxy, oxyalkylene, nitrile, ester, amino, nitro, amide, amido, imino, epoxy cyano and organosilicon groups. 

The reactions of 2- and 4-cyanoquinazolines are similar to those of the chloro compounds. Thus the cyano group can be replaced by alkoxide, phenoxide, substituted amino, and hydrazino groups substitution of the 4-cyano takes place more readily than that of the 2-cyano group.The nitrile substituent can also be hydrolyzed to an alkoxycarbonyl and amide group/ ... 

The synthetic potential of alkenylzirconium complexes is partially due to the fact that the hydrozirconation of alkynes can be carried out in the presence of some synthetically useful functional groups such as halide [80,153, 211, 212], acetals, amides, imides, carbamates, sulfides [186], ester, cyano [95, 213] and chiral propargyl amino functionalities [214]. 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

In order to clarify the possible existence of these intermediates, 6-chloro-5-cyano-4-phenyl[l(3)- N]pyrimidine (20) (the label is scrambled over both nitrogens) and the radioactive 6-chloro-5-[ " C-cyano]-4-phenylpyrimidine (23) were synthesized as substrates. Because of the presence of the cyano function at C-5, one can expect that 20 (and 23) would undergo amination involving an Sn(ANRORC) mechanism. This has indeed been found. When 20 was reacted with potassium amide in liquid ammonia, two products were obtained as main product, 6-amino-5-cyano-4-phenylpyrimidine (21, 75%), and as minor product, a-amino-jS,jS -dicyanostyrene (22, about 20%) (Scheme 11.15). 

Several variations of this synthetic route have been developed. For example, condensation of the methyltriazole (21) with thiourea gives the thiol derivative (22), and reaction with phosphoryl chloride in dimethylformamide converts the amino-amide to a cyano-amidine, which can be reduced to the 4-amino-5-aminomethyl derivative (Scheme 47). ... 

Methyl substituents in 3,4 -bipyridines have been oxidized by permanganate to the corresponding carboxylic acids, which are readily decar-boxylated, and esters have been converted to amides. 3,4 -Bipyridine-3 -sulfonic acid on fusion with potassium ferricyanide affords 3 -cyano-3,4 -bipyridine. Cyano-substituted 3,4 -bipyridines have been hydrolyzed to the amide or carboxylic acid, " and the amides were converted to amino groups. Hydroxyl substituents in the 2, 6, 6-positions of 3,4 -bipyridine have been replaced by chloro groups with phosphorus... 

One of useful building blocks for the synthesis of 2-(l//)-pyrazinones is iV-BOC amino acids, whose carboxylic acid moiety reacts with the amino group of another component having cyano or carbonyl functionality at the a-position, such as a-amino nitriles <2004T835>, a-amino amide (Scheme 46) <2000H(53)1559>, a-amino ketones... 

Cyclocondensation of ethyl 2-aminonicotinate in presence of HC(OEt)3 and various primary amines gave 22 3-substituted pyrido[2,3-,7]pyrimidin-4(377)-ones 371 <1995PHA719>. Fourteen 3,5,7-triarylpyrido[2,3-r7]pyrimi-dine-2,4(l/7,37/)-diones 372 have been prepared from the reaction of either 2-amino-3-cyano-4,6-diarylpyridines or the 3-carboxamido products of alcoholic KOH hydrolysis, with aryl isocyanates better yields were obtained from the amides <1995IJB740>. 4-Aminopyrido[2,3- pyrimidin-5(8//)-one 158 was synthesized by treatment of 2-amino-3-cyano-4-methoxypyridine with trimethylsilyl iodide to give the corresponding pyridin-4(177)-one, which was refluxed with formamidine acetate in ethoxyethanol to effect the cyclization <2000JME3704>. 

The pyrazolo-fused pyrimido[4,5-< ]-l,2,4-triazine 35 was synthesized using the 5-amino-6-cyano triazine 131 (Scheme 21) as the precursor. Reaction with phosgeniminium chloride gave the amide halide intermediate 132 which in turn produced the pyrimido[4,5-< ]-l,2,4-triazine 35 upon treatment with gaseous hydrogen chloride <1996T3037>. 

In summary, the direct insertion of zinc dust to organic halides is an excellent method for preparing a broad range of polyfunctional organozinc halides bearing various functional groups like an ester" , an ether, an acetate" , a ketone, cyano", halide" , N,N-bis(trimethylsilyl)amino °, primary and secondary amino, amide, phthalimide , sulfide, sulfoxide and sulfone , boronic ester , enone " or a phosphonate . An alternative method is based on transmetalation reactions. 

The search for RNAs with new catalytic functions has been aided by the development of a method that rapidly searches pools of random polymers of RNA and extracts those with particular activities SELEX is nothing less than accelerated evolution in a test tube (Box 26-3). It has been used to generate RNA molecules that bind to amino acids, organic dyes, nucleotides, cyano-cobalamin, and other molecules. Researchers have isolated ribozymes that catalyze ester and amide bond formation, Sn2 reactions, metallation of (addition of metal ions to) porphyrins, and carbon-carbon bond formation. The evolution of enzymatic cofactors with nucleotide handles that facilitate their binding to ribozymes might have further expanded the repertoire of chemical processes available to primitive metabolic systems. 

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