2-Amino-3-cyano-5- aminomethyl

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). ... 

To diethoxymethoxy-ethane malononitrile was added and ethoxymethylen-malononitrile was obtained. The ethoxymethylen-malononitrile reacted with acetamidine as a result 4-amino-5-cyano-2-methylpyrimidine was produced, which was reduced by H2/Raney-Ni to 4-amino-5-aminomethyl-2-methylpyrimidine. 

The 4-amino-5-aminomethyl-8-azapurines (e.g., 96), which were made by hydrogenating the 5-cyano analogs, provided a good approach to the synthesis of l,6-dihydro-8-azapurines, stable substances whose oxidation (see p. 139) furnished 8-azapurines unsubstituted in the 6 position. 

Cyanopyridines have been reduced to aminoethylpyridines by a variety of methods, 2- And 4-cyanopyridine are reduced with sodium borohydride to 2-and 4-aminomethylpyridine, respectively. In acidic solutions, the polaro-graphic reduction of 4-cyanopyridine yields 4-aminomethylpyridine. Hydrogenation of 6-chloro-5-cyano-4-methoxymethyl-3-nitro-2-picoline over palladium-charcoal in aqueous hydrochloric acid gives 3-amino-5-aminomethyl-4-methoxymethyl-2-picoline hydrochloride. 3-Amino-5-aminomethyl-2,4-lutidine is prepared in good yield by the catalytic reduction (Pd—C in methanol) of 6-chloro-3-cyano-2,4-dimethyl-3-nitropyri-dine. The hydrogenation of 3-( S-pyridylmethoxy)propionitrile over Raney Nickel yields 3-[(3-aminopropoxy)methyl] pyridine. ... 

Catalytic reductions of substituted pyridinecarboxylic acids continue to play an important role in some syntheses of pyridoxol. Thus 4-carbethoxy-6-chloro-5-cyano-2-methyl-3-nitropyridine (X-132) is reduced over Raney Nickel in water to 3-amino-5-aminomethyl-4-carboxy-2-methylpyridine-4,5-lactam (X-133). - ... 

Phenylpyrazine 1-oxide, 2,3-diphenylpyrazine 1-oxide and 2,5-diphenylpyrazine 1 -oxide have been deoxygenated in good yield by aqueous chromium(ll) chloride in methanol, acetone, and chloroform at room temperature (761), and deoxygenation of 5-(substituted aminomethyl)-2-amino-3-cyano-6-methylpyrazine 1-oxide by triethyl phosphite in hot dimethylformamide has been described (762). 

Branched derivatives of the type (75) have been transformed into /V-protected 3-amino-3-cyano-3-deoxy derivatives of the type (76) by a Hofmann rearrangement. The cyano group was also reduced to die aminomethyl group. 

Aminomethylation Reaction. The Hf(OTf)4-dopedMe3SiCl system was used as Lewis acid to catalyze the aminomethylation of electron-rich aromatic compounds. Suitable arenes include indoles, furans, pyrroles, thiophenes, and anilines, with new t)q)es of iV,0-acetals having a variety of functional groups, such as cyano, ester, bis(trimethylsilyl)amino, diallylamino, and cyclic amino moieties. This method allowed for the facile synthesis of nonnatural aromatic amino acid derivatives (eq 1). 4 Aminomethylation using a A, 0-acetal with a bis(trimethylsilyl)amino group was particularly successful in the direct preparation of a N-unsubstituted a-indolylglycine derivative, which required only a standard aqueous workup as the deprotective step. ... 

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