Pyrazinecarboxamide, 3,4-dihydro-6-methyl-3-oxo- (9CI) synthesis

Yield:88394-06-3 28%

Reaction Conditions:

Stage #1: 2-aminopropanediamide;2-oxopropanalwith sodium hydroxide in water at -20 - 20;
Stage #2: with hydrogenchloride in water at -20 - 20; for 48 h;

Steps:

An aqueous solution of NaOH (10.6ml_, 12.5N, 0.133mol) is added dropwise to a 40% water solution of pyruvic aldehyde (24g, 9.6g, 0.133mol) and 2-amino-malonamide (16g, 0.136mol) at -20⁰C, keeping the temperature bellow 0⁰C. The reaction mixture is mechanically stirred overnight at r.t and then the reaction mixture is cooled to -20⁰C and HCI cone. (16ml_, O.lβmol) is slowly added keeping the temperature bellow 0⁰C and stirred at r.t. for 48h. The reaction mixture is cooled in an ice bath and the crystals formed filtered off, washed with a little water and dried with air, to give 3-hydroxy-6-methyl-pyrazine-2-carboxylic acid amide as a brown solid, (5.7 g, 28%).

References:

WO2009/24585,2009,A2 Location in patent:Page/Page column 69-70