Electric Literature of 1458-16-8,Some common heterocyclic compound, 1458-16-8, name is Methyl 3-amino-6-iodopyrazine-2-carboxylate, molecular formula is C6H6IN3O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a dimethylformamide (60 ml) suspension of copper (II) bromide (19.2 g, 86.0 mmol) raised in temperature to 50C, t-butyl nitrite (5.7 ml, 43.0 mmol) was added and subsequently a dimethylformamide (60 ml) suspension of 3-amino-6-iodopyrazine-2-carboxylic acid methyl ester (see Patent Document: WO2006/015124)(12.0 g, 43.0 mmol) was added dropwise and the mixture was stirred for one hour. The reaction mixture was charged with t-butyl nitrite (11.4 ml, 86.0 mmol) and was further stirred for 30 minutes at an external temperature of 50C. The reaction solution was poured into a 3 M aqueous hydrochloride solution (60 ml) of sulfamic acid (7.6 g) under ice cooling and extracted with ethyl acetate, dried (over anhydrous magnesium sulfate), filtered and concentrated to obtain a residue, which was purified by silica gel column chromatography [developing eluent: hexane: ethyl acetate = 5:1 to 1:1]. The resultant low polarity product was washed with hexane-ethyl acetate to obtain 3-bromo-6-iodopyrazine-2-carboxylic acid methyl ester (6.38 g) in the form of a white solid substance. A high-polarity product was washed with ethyl acetate to obtain 3-hydoxy-6-iodopyrazine-2-carboxylic acid methyl ester (2.70 g) in the form of a yellow solid substance. 3-Bromo-6-iodopyrazine-2-carboxylic acid methyl ester MS (ESI): 342 (M+1) 1H NMR (300 MHz, CDC13) delta ppm 4.02 (d, J = 0.55 Hz, 3 H) 8.72 (s, 1 H) 3-Hydoxy-6-iodopyrazirie-2-carboxylic acid methyl ester MS (ESI): (ES+) 281 (ES-) 279 1H NMR (300 MHz, DMSO) delta ppm 3.82 (s, 2.53 H) 3.84 (s, 0.47 H) 8.35 (s, 0.78 H) 8.39 (s, 0.22 H) 12.69 – 13.03 (br, 1 H)
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Methyl 3-amino-6-iodopyrazine-2-carboxylate, its application will become more common.
Reference:
Patent; Taisho Pharmaceutical Co. Ltd.; Nissan Chemical Industries, Ltd.; EP2157090; (2010); A1;,
Pyrazine – Wikipedia,
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