Synthetic Route of 113305-94-5,Some common heterocyclic compound, 113305-94-5, name is 5-Aminopyrazine-2-carbonitrile, molecular formula is C5H4N4, 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.
5-Aminopyrazine-2-carbonitrile (5.45 mg, 0.045 mmol), Xantphos (1.749 mg, 3.02 mumol), tris(dibenzyiideneacetone)dipalladium(0) (1.384 mg, 1.511 mumol), and cesium carbonate (24.62 mg, 0.076 mmol) were added to tert-butyl 4-((2-chloro-5-(4-methoxyphenyl)pyridin- 4-ylamino)methyl)-4-fluoropiperidine-1-carboxylate (17 mg, 0.038 mmol) in a 0.2 mL microwave reaction vial. The vial was sealed and an inert atmosphere was introduced before dry dioxane (291 muL) was added. Nitrogen was bubbled through the mixture for 5 min. The mixture was heated at 150 0C for 1 hr by microwave irradiation. After cooling the mixture was diluted with 20% dichloromethane in MeOH and loaed onto a preparative thin layer chromatography plate. Elution with 50% EtOAc in hexane gave tert-butyl 4-((2-(5- cyanopyrazin-2-ylamino)-5-(4-methoxyphenyl)pyridin-4-ylamino)methyl)-4- fluoropiperidine-1-carboxylate (1.5 mg, 2.81 mumol, 7% yield) as a light yellow powder. LCMS (4) Rt = 2.35 min; m/z (ESI+) 534 (MH+). Trifluoroacetic acid (0.1 mL, 1.298 mmol) was added to tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-(4-methoxyphenyl)pyridin-4- ylamino)methyl)-4-fluoropiperidine-1-carboxylate (1.5 mg, 2.81 mumol) dissolved in dichloromethane (0.5 mL) and the solution was stirred for 1 hr. The volatiles were removed in vacuo and the crude product was purified by ion exchange on lsolute SCX Il acidic resin (1 g), followed by preparative thin layer chromatography, eluting with 10% MeOH / 1% NH3 / 89% dichloromethane, to give 5-(4-((4-fluoropiperidin-4- yl)methylamino)-5-(4-methoxyphenyl)pyridin-2-ylamino)pyrazine-2-carbonitrile (1 mg, 2.307 mumol, 82% yield) as a yellow powder.1H NMR (500 MHz, MeOD) delta 8.87 (s, 1 H), 8.59 (s, 1 H), 7.75 (s, 1 H), 7.33 (d, 2H, J = 8.5 Hz), 7.21 (s, 1 H), 7.07 (d, 2H, J = 8.5 Hz), 3.86 (s, 3H), 3.44 (d, 2H, J = 19.5 Hz), 3.08- 2.93 (m, 4H), 1.96-1.69 (m, 4H). LCMS (4) Rt = 1.62 min; m/z (ESI+) 434 (MH+).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Aminopyrazine-2-carbonitrile, its application will become more common.
Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; WO2009/44162; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem