ChemicalBook CAS DataBase List 2-Amino-6-methylpyrazine

2-Amino-6-methylpyrazine synthesis

11synthesis methods

Product Name:2-Amino-6-methylpyrazine
CAS Number:5521-56-2
Molecular formula:C5H7N3
Molecular Weight:109.13

930798-25-7
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$72.00/250mg

5521-56-2
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$33.00/200mg

Yield: 71%

Reaction Conditions:

with ammonia in water at 180; under 26252.6 Torr; for 8 h;sealed vessel;

Steps:

1.c
60ml) at O⁰C was added, diethylmalonate (2.1moleq) in THF (60ml) and 2,6- dichloropyrazine (2Og) in THF (40ml). The mixture was then heated to reflux for 18hrs before being allowed to cool and 2M Hydrochloric acid (100ml) added. The resulting two layers were separated and the THF layer partially concentrated under vacuum to give a solution containing 2-(6-chloro-pyrazin-2-yl)-malonic acid diethyl ester. This solution was EPO then cooled to 10⁰C and 2M sodium hydroxide (328ml) added. After stirring for 24hrs the mixture was washed with methyl isobutyl ketone [MIBK] (200ml) and the organic layer discarded. The aqueous layer containing 2-(6-chloro-pyrazin-2-yl)-malonic acid was then added to 6M hydrochloric acid (135ml), maintaining a reaction temperature of 20-25°C to facilitate the decarboxylation.The resulting 6-chloro-pyrazin-2-yl-acetic acid partially precipitated from the mixture, but for ease of isolation was extracted into MIBK (130ml), dried using MgSO₄, filtered and evaporated to give a yellow solid. The resulting crude solid 22.4g was then crystallised from methyl-t-butyl ether (MTBE) to give pure 6-chloro-pyrazin-2-yl-acetic acid , 15.4g 67% yield based on 2,6-dichlorpyrazine.The 6-chloro-pyrazin-2-yl-acetic acid (20.Og) was then treated with aqueous ammonia (120ml) in a sealed vessel at 180°C (35 bar) for 8hrs. The mixture was then cooled to 20°C and water (40ml) added, before being concentrated under vacuum to remove the ammonia. The product was extracted into ethyl acetate and the solution treated with charcoal, before being dried using MgSO₄, filtered and evaporated to give 6-methyl-2-pyrazin-2-ylamine as a pale green solid 9.Og, 71% yield based on 6-chloro-pyrazin-2-yl-acetic acid. Analysis 2-(6-Chloro-pyrazin-2-yl)-malonic acid diethyl esterMS (EI +ve) 273/275 (M+H) IH NMR (CDCl₃) :δ 8.7 (IHs), 8.5 (IHs), 4.9 (IHs), 4.2(2x2Hq), 1.2 (2x3Ht).6- Chloro-pyrazin-l-yl-acetic acidMS (EI +ve) 173/175 (M+H)IHNMR (CDCl₃) :δ 8.55 (IH s), 8.50 (IH s); 3.9 (2Hs).6-Methyl-2-pyrazin-2-ylamine MS (GC/MS) : 100% RT 2.0mins, M+H = 110IHNMR (CDC13) : δ 7.8 (IHs), 7.8 (IHs), 4.4 (2H bs), 2.4 (3Hs). Mpt : 124-125⁰C

References:

ASTRAZENECA AB WO2007/35153, 2007, A1 Location in patent:Page/Page column 2; 4-5

544-97-8 Synthesis