2-AMINO-3,5-DICHLOROPYRAZINE

2-Amino-3-chloropyrazine 9 (10.0 g, 77.2 mmol) was added to a stirred suspension of NCS (11.6 g, 86.9 mmol) in chloroform (73 mL). The reaction mixture was heated at reflux for 4 h. The solution was cooled and partitioned between chloroform (180 mL) and water (2*50 mL). The organic layer was dried, filtered and concentrated. Flash chromatography on silica, eluting with chloroform, gave 10 (9.66 g, 76percent) as a pale yellow solid. Mp 200-202 °C; R2-Aminopyrazine (0.50 g, 5.26 mmol) was dissolved in THF (50 mL), and N-chlorosuccinimide (1.62 g, 12.1 mmol) was added to the solution with stirring. The mixture was refluxed at 100 °C for 10 h. After cooling, solvent was evaporated. The residue was directly purified by column chromatography. Finally, the obtained product was washed with pentane/diethyl ether (5:1) to 2-Amino-3, 5-dichloropyrazine 1b (492 mg, 57percent) as a slightly yellow solid. Initial attempt showed that the reaction gave a lot of black polymers after a few To a stirred solution of Similar procedure to step 3 of the was followed to arrive at compound 255 with LC-MS [M+H] -m/z 388.To the solution of 229 (100 mg, 0.39 mmol) in dried THF (10mL) was added t-BuOK (44 mg, 0.39 mmol) . The mixture was stirred at room temperature for 10min, then was added 2-nitro-3-fluoro-5-chloropyridine (69 mg, 0.39 mmol) and continued to stirred at room temperature for 1h. The reaction was quenched with silica gel (1g) , and purified by column chromatography to give the desired product (153 mg, 95%) .In a flask, under an inert atmosphere of argon, was added Into a flask, under an inert atmosphere of nitrogen, was placed 1, 1, 1, 2, 2-pentafluoro-4-iodobutane (21.7 g, 79 mmol), zinc metal (8.4 g, 128 mmol) and DMA (60 mL). This was followed by the dropwise addition of a solution of iodine (0.77 g, 3.05 mmol) in DMA (4 mL). The resulting mixture was stirred for 3 h at 80C. The reaction was cooled and directly used in the next step. In a flask, under an inert atmosphere of argon, was added STEP4 Preparation of 6, 8-dichloro-3-((3aR, 4S, 6aS)-2, 2-dimethyltetrahydrothieno[3, 4-d][1, 3]dioxol-4-yl)imidazo[1, 2-a]pyrazine COCl2 (2.13 ml, 4.27 mmol) was added dropwise over 15 min to a solution of dimethylsulfoxide (0.39 g, 4.98 mmol) in DCM (30 mL) cooled with a dry ice-acetone bath. To this solution was added a solution of (S)-2-chloro-2-((3aR, 4R, 6aS)-2, 2-dimethyltetrahydrothieno[3, 4-d][1, 3]dioxol-4-yl)ethanol (0.85 g, 3.56 mmol) over 5 min. The mixture was further stirred at -78 C. for 45 min. TEA (0.26 ml, 1.89 mmol) was added to the solution, stirred at -40 C. for 30 min and allowed to warm up to room temperature. The organic phase was washed with sat. NH4Cl solution and brine, dried over Na2SO4 and filtered. After removal of the solvent, the resulting residue (760 mg) was dissolved in CH3CN. To this solution was added Step 1: Preparation of 2-(3-amino-6-chloro-pyrazin-2-ylamino)-butan-l-ol Neat reaction between 3, 5-dichloro-pyrazin-2-ylamine (1 g, 4.6 mmol) and 2-amino- butan- l-ol (1.23 g, 13.8 mmol) was carried out under microwave at 120 C for 1 hour. Then the mixture was partitioned between EtOAc and brine. The aqueous layer was separated and then extracted with EtOAc. The combined organic layers were concentrated, and then the residue was purified by column chromatography to give 600 mg of 2-(3-amino-6-chloro-pyrazin-2-ylamino)- butan-l-ol.

Molecular Weight:163.99
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:162.9704025
Monoisotopic Mass:162.9704025
Topological Polar Surface Area:51.8
Heavy Atom Count:9
Complexity:99.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes