Malonic acid, 2-amino-2-methyl synthesis

The variety of educts and products of the higher MCRs is illustrated here. Product 72 (Scheme 1.18) is formed from the five functional groups of lysine, benzaldehyde, and tert-butylisocyanide. The synthesis of 73 is achieved with hydrazine, furanaldehyde, malonic acid, and the isocyano methylester of acetic acid, compound 74 results from the reaction of benzylamine, 5-methyl-2-furanaldehyde, maleic acid mono-ethylester, and benzylisocyanide. ° Zhu et al. prepared a variety of related products, such as, 75, from (9-amino-methyl cinnamate, heptanal, and a-isocyano a-benzyl acetamides. 

The reaction of 2-amino-3-nitrosopyridines with compounds containing an activated methylene group permits unambiguous synthesis of various derivatives of pyrido[2,3-b]pyrazine. For example, the pyridine 58 reacts in the presence of sodium ethoxide with a variety of arylacetonitriles and cyanoacetic acid derivatives to provide various 2-substituted 3-amino compounds (59). " " Diethyl malonate reacts similarly to give the 2-carboxylic acid 60, its ester being presumably hydrolyzed in the alkaline reaction conditions. Ethyl acetoacetate yields the 2-acetyl-3-oxo compound 61, and acetylacetone ° provides the 2-acetyl-3-methyl compound 62. The latter condensation proceeds poorly in ethanolic sodium ethoxide, but heating the nitroso compound with acetylacetone under reflux in pyridine gives a 59% yield of the product 62. °... 

Isotopic atoms have been introduced into amino acids or molecules employed in the synthesis of amino acids, by (a) catal]rtic addition of D to carbon-carbon double bonds (161, 459, 758, 852), (b) methylation with trideuteromethyliodide (831, 833), (c) syntheses of deuteromalonio ester derivatives from u-phenyl deuteroalkyl bromides and malonic ester (626), (d) preparation of deutero amino acids by reaction of amino acids with deuterosulfuric acid (576, 667, 692, 758, 805, 852), (e) catalytic reduction with DgO and amination of a-keto acids (668), (f) preparation of deuteroaliphatic acids by reaction of aliphatic acids with DjO (690), (g) catalytic reduction and amination with of a-keto acids (690,... 

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