Synthesis
GENERAL STEPS: Chloroacetyl chloride (0.2 mol, 15.9 mL, CAS: 79-04-9) was slowly added dropwise to a solution of dichloromethane (50 mL) containing n-butylamine (0.2 mol, 14.83 g) in an ice bath. After the dropwise addition, 20% NaOH aqueous solution was added and the reaction mixture was warmed up to room temperature and stirring was continued for 2 hours. After completion of the reaction, the organic phase was separated and washed sequentially with 5% aqueous HCl and 5% aqueous NaHCO3 (3 x 25 mL each). The organic phase was dried and filtered, and then the solvent was removed by distillation under reduced pressure to give the intermediate N-butyl-2-chloroacetamide (92% yield). Subsequently, the intermediate (0.05 mol, 9.00 g) was mixed with 5,6,7,8-tetrahydropyrido[1,2-α]imidazole (0.05 mol, 6.11 g, CAS: 34167-66-3) in acetonitrile (50 mL) and the reaction was carried out at reflux for 18 hours. The reaction solution was recrystallized by ethyl acetate recrystallization operation to give the product [4C-imCH2CONHBu]Cl (89% yield). Finally, [4C-imCH2CONHBu]OH was obtained by treatment with anion exchange resin.
References
[1] Patent: CN104326949, 2016, B. Location in patent: Paragraph 0060; 0061; 0063
[2] Patent: WO2007/9083, 2007, A2. Location in patent: Page/Page column 68
[3] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 6, p. 678 - 681
[4] ChemMedChem, 2018,
[5] Organic Letters, 2004, vol. 6, # 26, p. 4805 - 4808
