Norman L. Colbry

Synthesis of 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones via directed lithiation of 2-substituted 5-aminopyridine derivatives

Directed lithiation of Boc or pivaloyl derivatives of 2-substituted 5-aminopyridines with BuLi–TMEDA in diethyl ether at –10 °C gave 4-lithio derivatives which were quenched with CO2 to give the analogous C-4 carboxylic acids. Hydrolysis of the protecting groups with either TFA or aqueous KOH gave 2-substituted 5-aminopyridine-4-carboxylic acids which were converted to 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones by reaction with formamide or, more optimally, formamidine acetate. Boc protected aminopyridines provided the best overall results, with synthesis of these derivatives best achieved by direct reaction of the aminopyridine with di-tert-butyl dicarbonate in the absence of added base.

A simple method for preparation of N-mono- and N,N-di-alkylated α-amino acids

Abstract Reactions of α-amino acids with ketones under hydrogenation conditions using 20% Pd(OH) 2 /C as the catalyst gave N -mono-alkylated amino acids in high yields. Reductive methylation of N -mono-alkylated amino acids under the same hydrogenation conditions at 50°C afforded N , N -di-alkylated amino acids in excellent yields. This simple method has been used to synthesize N -mono- and N , N -di-alkylated amino acids on a scale of 200 g.