Aminopyrazine → HCID 178522391, compound

Participants

Reaction Steps

To a solution of pyrazin-2-amine (284 mg, 2.99 mmol) in dry THF (12 mL) was added 2M solution of isopropylmagnesium chloride (1.5 mL, 2.99 mmol) in THF dropwise under nitrogen at 0° C. The resultant mixture was stirred at 0° C. for 20 min. To this solution was added a solution of methyl 1-(4-(3-cyclopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxylate (200 mg, 0.746 mmol) in THF (2 mL) dropwise at 0° C. and the reaction mixture was allowed to stir at RT for 1.5 h. The reaction was quenched with saturated ammonium chloride solution (20 mL). The product was extracted with EtOAc (2×40 mL) and the organic layer was dried over anhydrous sodium sulfate. Removal of EtOAc under reduced pressure afforded an oily residue that was purified by reverse phase HPLC to afford 1-(4-(3-cyclopropyl-1H-pyrazol-5-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)-N-(pyrazin-2-yl)pyrrolidine-2-carboxamide (120 mg). 1H NMR (400 MHz, CD3OD, freebase) δ (ppm): 0.57-0.67 (m, 2H), 0.78-0.95 (m, 2H), 1.70-1.81 (m, 1H), 2.02-2.18 (m, 4H), 2.25-2.39 (m, 2H), 2.63-2.78 (m, 2H), 2.79-2.85 (m, 2H), 3.60-3.77 (m, 1H), 3.78-3.94 (m, 1H), 4.73-4.81 (m, 1H), 6.25 (s, 1H), 8.26 (d, 1H), 8.30 (s, 1H), 9.31 (s, 1H). Separation by chiral HPLC provided enantiomers 6a and 6b.

Provenance & Evidence