Acetyl chloride → HCID 178473831, compound

Participants

Reaction Steps

To a stirred suspension of [(S)-1-(1-piperidin-4-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine 113 (46 mg, 0.127 mmol) and DIPEA (26 μL, 0.152 mmol) in anhydrous THF (3 mL) and anhydrous DCM (1 mL) was added acetyl chloride (9 μL, 0.127 mmol). Stirring at RT was continued for 3 h then volatiles were removed under reduced pressure and the resulting residue was partitioned between EtOAc and water. The aqueous layer was further washed with DCM and the organic layers were then washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residues were combined, purified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-70% 0.1% HCO2H in acetonitrile/water) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated under reduced pressure affording 115 as a white solid (10 mg, 19%). LCMS: RT 2.13 min [M+H]+ 405.1. 1H NMR (CDCl3, 400 MHz): δ 8.35 (1H, s), 7.88 (1H, s), 7.78-7.70 (1H, m), 7.49-7.42 (1H, m), 7.28-7.20 (3H, m), 6.05 (1H, s), 4.98-4.82 (1.5H, m), 4.71-4.61 (0.5H, m), 4.09-3.99 (0.5H, m), 3.90-3.78 (0.5H, m), 3.42-3.37 (0.5H, m), 3.32-3.18 (0.5H, m), 2.88-2.37 (1H, m), 2.20-2.10 (4H, m), 2.06-1.96 (1H, m), 1.90-1.69 (5H, m). Signals split due to presence of rotamers

Provenance & Evidence