Aminopyrazine → (S)-2-Methyl-N-(pyrazin-2-yl)pyrrolidine-2-carboxamide

To a stirred solution of pyrazin-2-amine (1.56 g, 16.44 mmol) in THF (30 ml) was added isopropyl magnesium chloride (7.8 ml, 15.62 mmol) (2.0 M THF solution) dropwise at 0° C. under nitrogen. The resulting suspension was stirred at RT for 30 min. A solution of (S)-1-tert-butyl 2-methyl 2-methylpyrrolidine-1,2-dicarboxylate (1.0 g, 4.11 mmol) solid was added to the reaction mixture. The reaction mixture was stirred at RT for 6 h, quenched with MeOH, and concentrated. The residue was dissolved in EtOAc (120 ml) and washed with 1N HCl to remove the excess pyrazin-2-amine, water, and brine, dried over Na2SO4. The crude product was dissolved in methanol and 4N HCl in dioxane (4 mL) was added. The reaction mixture was stirred at room temperature overnight and the crude product was used in the next step without further purification.

1. stirringThe reaction mixture was stirred at RT for 6 h
2. customquenched with MeOH
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in EtOAc (120 ml)
5. washwashed with 1N HCl
6. customto remove the excess pyrazin-2-amine, water, and brine
7. dry with materialdried over Na2SO4
8. dissolutionThe crude product was dissolved in methanol
9. addition4N HCl in dioxane (4 mL) was added
10. stirringThe reaction mixture was stirred at room temperature overnight
11. customthe crude product was used in the next step without further purification

ORD record

ord-53ccca1c357e4b07a2af256d5f13d079

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415340B2