Nitrogen → 8-Chloro-3-(3-methylenecyclobutyl)imidazo[1,5-a]pyrazine

Participants

Reaction Steps

N-[(3-Chloropyrazin-2-yl)methyl]-3-methylenecyclobutanecarboxamide (52.1 g, 219.2 mmol) in anhydrous MeCN (1.0 L) was treated with DMF (1.0 mL) and POCl3 (100 mL, 1.09 mol) and the mixture was stirred at 55° C. for 30 min. under a gentle stream of N2. The reaction was then concentrated in vacua and the residue reconstituted in CH2Cl2 and treated with cold 2.0 M NH3 in IPA. This mixture was concentrated in vacua, water added to dissolve the salts, and then extracted with CH2Cl2 (4×60 mL). The organic layers where combined and washed with sat. NaHCO3 (1×70 mL) dried over sodium sulfate, filtered and concentrated in vacua. The crude material was purified by chromatography over silica gel eluting with 2:1 hexane: EtOAc to yield desired product. 1H NMR (400 MHz,CDCl3) δ ppm 3.24-3.30 (4 H, m), 3.78-3.85 (1 H, m), 4.89-4.94 (2 H, m), 7.33 (1 H, d, J=4.99 Hz), 7.53 (1 H, d, J=5.09 Hz) and 7.82 (1 H, s). MS (ES+): m/z 220.28 and 222.30 [MH+].

Provenance & Evidence