Acrylonitrile → HCID 178461904, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of [(S)-1-(1-piperidin-4-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine 113 (75 mg, 0.207 mmol) and acrylonitrile (75 μL, 1.14 mmol) in IMS (3 mL) was stirred in a sealed tube at 70° C. for 3 h. After cooling to RT, the crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined, concentrated in vacuo and purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM), followed by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-60% 0.1% NH4OH in acetonitrile/water) and finally loaded into an Isolute® SCX-2 which was washed with MeOH and the product eluted with 2M NH3/MeOH. The ammonia fractions were combined and concentrated in vacuo affording 126 as a white solid (28 mg, 33%). LCMS: RT 1.67 min [M+H]+ 416.1. 1H NMR (CDCl3, 400 MHz): δ 8.52 (1H, s), 7.96 (1H, s), 7.80-7.73 (1H, m), 7.65-7.59 (1H, m), 7.26-7.08 (3H, m), 5.29 (1H, bs), 4.69-4.57 (1H, m), 3.09 (1H, bd, J=11.28 Hz), 2.90 (1H, d, J=11.11 Hz), 2.76-2.60 (3H, m), 2.37-2.25 (3H, m), 2.30-2.30 (1H, m), 1.98-1.66 (7H, m)

Provenance & Evidence