3-Chloro-pyrazine-2,6-diaMine synthesis

Yield:794497-98-6 82%

Reaction Conditions:

Stage #1: 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl esterwith lithium hydroxide;water in methanol at 90; for 1.5 h;
Stage #2: with hydrogenchloride in 1,4-dioxane;water at 100; for 2 h;
Stage #3: with sodium carbonate in water; pH=8;

Steps:

14

Preparation 14 3-Chloro-pyrazine-2,6-diamineLithium hydroxide (12.4g, 0.30 mol) was added to a stirred suspension of 3,5-diamino- 6-chloro-pyrazine-2-carboxylic acid methyl ester (20 g, 99 mmol) in methanol (300 ml) and water (120 ml) and the reaction heated at 9O⁰C for 1.5 hours before allowing to cool to room temperature. The reaction was concentrated in vacuo to afford a yellow slurry and this was suspended in 1 ,4-dioxane (350 ml) and 2M aqueous HCI solution (200 ml,) was added. The mixture was heated at 100 ⁰C for 2 hours and then allowed to cool before removing the 1 ,4-dioxane in vacuo. The resulting aqueous solution was taken to pH 8 using sodium carbonate (saturated aqueous) and extracted into ethyl acetate (3 x 300 ml). The combined organic layers were washed with brine (300 ml), dried (Na₂SO₄) and concentrated in vacuo to afford a yellow solid (11.7g, 82%).¹HNMR(d6-DMSO): 5.95(br s, 2H), 6.02(br s, 2H), 6.82(s, 1 H).

References:

WO2008/135830,2008,A1 Location in patent:Page/Page column 61