128550-06-1

128550-05-0

128550-06-1

The general procedure for the synthesis of tert-butyl (3-((3-aminopropyl)(tert-butoxycarbonyl)amino)propyl)(4-((tert-butoxycarbonyl)(3-((tert-butoxycarbonyl)amino)propyl)amino)butyl)carbamate from the compound (CAS:128550-05-0) is as follows: Example 3M-Substituted homo spermine-sulfonamide analogs (Table B: HOMO-SPM) - Synthesis of N1-hexadecylsulfonyl-1,18-diamino-5,9,14-triaza-octadecane tetrahydrochloride MQTS 2383: 2.6 g (6.5 mmol) of raw material was dissolved in 120 mL of anhydrous methanol, 1 mol % triBoc-spm was added , followed by the addition of 0.85 mL of acrylonitrile. The reaction mixture was stirred at room temperature for 18 hours after which the reaction was confirmed to be nearly complete by TLC analysis (unfolding agent: CH2Cl2/MeOH/NH4OH, 90:8:2). The solvent was removed by evaporation, the oily residue was dissolved in 100 mL of dichloromethane and 3.06 g (14 mmol, 2.15 equiv) of di-tert-butyl dicarbonate (Boc2O) was added. After 16 hours of reaction, the solvent was removed by evaporation and the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate, 3:2) to give 2.8 g (66% yield) of monoalkylated product as a colorless oil. The intermediate was dissolved in 30 mL of glacial acetic acid and 3 g of Pd(OH)2 catalyst was added. The mixture was placed under 50 psi hydrogen pressure and the reaction was shaken for 15 hours. Upon completion of the reaction, the catalyst was removed by filtration through a diatomaceous earth pad, the pads were washed with methanol, and the filtrates were combined and evaporated to give the crude product as a colorless oil. The crude product was further purified by silica gel column chromatography (eluent: CHCl3/MeOH/concentrated NH4OH, 92:8:2) to give 2.0 g (71% yield) of colorless oil. This intermediate can also be used to synthesize the branched HOMO-spermine analog shown in Table D (see Example 5). 0.20 g (0.30 mmol) of the above intermediate was dissolved in 7 mL of anhydrous dichloromethane, 0.063 mL (1.5 eq.) of triethylamine was added followed by the addition of 0.15 g (1.5 eq.) of solid cetylsulfonyl chloride at 25°C. The reaction mixture was diluted with dichloromethane and washed sequentially with ice-cold 0.1 N HCl, water and brine. The organic phase was dried and evaporated to give the crude product. Purification by silica gel column chromatography (eluent: hexane/ethyl acetate, 2:1) gave 0.171 g (65% yield) of the product as a colorless oil. The product was dissolved in 5 mL of methanol and treated with 5 mL of 6N HCl at 25 °C. The resulting colorless solution was stirred for 8 h. Evaporation gave 0.121 g (97% yield) of MQTS 2383 as a white solid in its tetrahydrochloride form.1H NMR (D2O, ppm): 3.05 (br s, 16H), 2.08 (br s, 4H), 1.90 (br s, 2H), 1.73 (m, 6H), 1.22 (m, 28H) , 0.78 (br s, 3H). Elemental analysis (calculated values: C29H69Cl4N5O2S): C, 50.21; H, 10.02; N, 10.09. measured values: C, 50.17; H, 9.96; N, 10.11. m/z 548 was observed at 11.7 min retention time for LC/MS analysis by ESI+ mode.