2-Amino-3-chloropyrazine

2, 3-Dichloropyrazine (5.0 g, 33.6 mmol) and 28percent ammonia water (20 mL) were placed in a tube, sealed and stirred at 100° C. for 18 hours. The reaction solution was diluted with water, the resultant solid substance was obtained by filtration to obtain 3-chloropyrazine-2-amine (3.46 g, 100percent) as a white solid substance.MS (ESI) m/z=130 (M+H)A suspension of 2, 3-dichloropyrazine (3.5 g, 0.023 mol) in 25 percent aqueous ammonia (20 mL) and THF (20 mL) was heated at 100°C for 18 h in a steel bomb. The reaction was cooled to ambient temperature and the resulting crude material was evaporated to minimum. The residual material was triturated with water (15 mL), filtered and dried to afford 2-amino-3-chloropyrazine as a buff- coloured crystalline solid (2.75 g, 90percent). MS (ES+) m/z: 130. [0440] To 2, 3-dichloropyrazine (20.0 g, 135 mmol) in a 250mL sealed tube was added NH40H (50.0 g, 1.43 mol). Theresulting solution was stirred overnight at 100° C. After coolingto rt, the solids were collected by filtration and washedwith Et20 to obtain compound 1a as a white solid (15.0 g, 86percent yield). Mass Spectrum (LCMS, ESI pos.): Calcd. forC4H4ClN3 : 130.0 (M+H). found: 130.2.2- Amino-3 -chloro-pyrazine[00236] 2, 3-Dichloropyrazine (2.5 g, 16.78 mmol) was dissolved in NH4OH (aq.) and the reaction mixture heated for 15 minutes at 150 C under microwave activation. Upon cooling a precipitate formed which was collected by filtration, washed with water and dried in vacuo at room temperature for 16 hours to give the title compound as a white, crystalline solid2, 3-Dichloro-pyrazine (14.8 g, 0.1 mol) was added in a 100 mL autoclave which contained 50 mL of the solution of N' aqueous with stirring, and then the reaction mixture was warmed to 100°C and stirred overnight, Cooled to room temperature. Filtrated, the solid was washed with water and further with dichloromethane to afford a solid, which dried on vacuum to afford 3-Chloro-pyrazin-2-ylamine. (10 g, 80percent yield). LC/MS (ESIStep A: Preparation of 3-Chloro-pyrazin-2-ylamine1.5 L aqueous ammonia (25 percent) were added to 163 g 2, 3-dichloro-pyrazine and the mixture was heated in a pressure tube under stirring for 1 h to 160° C. After cooling, the brwon suspension was filtered and the residue was washed with water and dried in vaccuo to yield 107.5 g (77.4 percent) of the title compound. A mixture 2, 3-dichloropyrazine (50 g, 0.34 mmol) and concentrated aqueous ammonium hydroxide (200 mL) was stirred at 85° C. in a closed pressure vessel for 4 days. The mixture was cooled to 25° C., water (200 mL) was added, and the mixture was filtered. The solid was washed with water (400 mL), then with dichloromethane (400 mL) and dried under vacuum. Compound 100 was isolated as a white solid 32.5 g (73percent). SYNTHESIS; Example 100; A mixture 2, 3-dichloropyrazine (50 g, 0.34 mmol) and concentrated aqueous ammonium hydroxide (200 mL) was stirred at 85° C. in a closed pressure vessel for 4 days. The mixture was cooled to 25° C., water (200 mL) was added, and the mixture was filtered. The solid was washed with water (400 mL), then with dichloromethane (400 mL) and dried under vacuum. Compound 100 was isolated as a white solid 32.5 g (73percent). 2, 3-Dichloropyrazine 5 (5.0 g, 33.6 mmol) in 28percent aqueousammonia solution (20 mL) in a reactor Parrwas stirred at 100 C for17 h. After cooling, the resulting mixture was filtered, the solid waswashed with water and dried in vacuo to afford compound 6 (3.0 g, 70percent) as a white powder. Rf 0.37 (cyHex/EtOAc 1:1); Mp: 170 C (lit.[43]: 169.4e170.1 C); 1H NMR (400 MHz, DMSO-d6): d 6.83 (bs, 2H, NH2), 7.60 (d, 1H, J 2.4 Hz, H5), 7.98 (d, 1H, J 2.4 Hz, H6); 13C NMR(100 MHz, DMSO-d6): d 130.6 (CH), 132.6 (C), 141.4 (CH), 152.7 (C);MS (ESI) m/z (percent): 129.8 (100) [MH], 131.8 (40). [MH2].A thick-walled reaction vessel (250 mL) charged with 2, 3-dichloropyrazine (14.9 g, 95 mmol) and 28-30percent ammonium hydroxide (75 mL) was sealed in vacuo, submitted to a freeze-pump- thaw cycle and then heated with stirring to 135 °C for 15 h. Upon cooling of the reaction mixture, needles were observed to form from the reaction mixture. The supernatant was decanted off and the residual solid was solubilized in hot methanol. The methanol solution was concentrated in vacuo and the resultant crude material (10. 8 g) was recrystallized from methanol (150 mL) to yield 8.26 g of the title compound (67percent yield). mp 167-168 °C ; Rf 0.5 (EtOAc-hexanes, 1 : 1, v/v, +0.5percent v/v iPrNH2) ;'H NMR (DMSO-d6) 8 8.9 (s, 1H), 8. 7 (s, 1H), 5.0 (br s, 2H)A thick-walled reaction vessel (250 mL) charged with 2, 3-dichloropyrazine (14.9 g, 95 mmol) and 28-30percent ammonium hydroxide (75 mL) was sealed in vacuo, submitted to a freeze-pump- thaw cycle and then heated with stirring to 135 °C for 15 h. Upon cooling of the reaction mixture, needles were observed to form from the reaction mixture. The supernatant was decanted off and the residual solid was solubilized in hot methanol. The methanol solution was concentrated in vacuo and the resultant crude material (10. 8 g) was recrystallized from methanol (150 mL) to yield 8.26 g of the title compound (67percent yield). mp 167-168 °C ; Rf 0.5 (EtOAc-hexanes, 1 : 1, v/v, +0.5percent v/v iPrNH2) ;'H NMR (DMSO-d6) 8 8.9 (s, 1H), 8. 7 (s, 1H), 5.0 (br s, 2H)2, 3-Dichloropyrazine (5.00 g, 33.56 mmol, 1.00 eq) was mixed with ammonia (68.27 g, 1.95 mol, 58.04 eq). A suspension of 2, 3-dichloropyrazine (35 g, 0.23 mol) in 25percent aqueous ammonia (200 ml) was heated at 100°C for 12 h in a PTFE-lined pressure reactor (terminal pressure 100 psi). The reaction was cooled to ambient temperature and the resulting crystalline solid collected by filtration. This solid was triturated with water (150 ml) and dried to afford 2-amino-3-chloropyrazine as a buff- coloured crystalline solid (28 g, 92percent):

Molecular Weight:129.55
XLogP3:0.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:129.0093748
Monoisotopic Mass:129.0093748
Topological Polar Surface Area:51.8
Heavy Atom Count:8
Complexity:77.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes