反应详情

12N HCl (15 mL) was added dropwise to an ice cooled solution of N-(4-{4-[2-(N′,N″-di-tert-butoxycarbonylguanidino)ethoxy]phenyl}butyl)-1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-guanidine 5 (370 mg, 0.56 mmole) in methanol (15 mL) over 1 min. After the addition, the cooling bath was removed, and the reaction was allowed to stir for 30 min. TLC (silica gel, methylene chloride/methanol/concentrated ammonium hydroxide, 3:3:1) indicated slow reaction progression. An additional 15 mL of 12N HCl was added dropwise at room temperature, and after 2 h, TLC indicated reaction completion. The solvent was evaporated and methanol (100 mL) was added and then evaporated below 30° C., this process was repeated a further three times and then the residue was placed under vacuum at 40° C. for 2 days to afford 300 mg (96%) of the pure product as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 1.57 (m, 4H), 2.56 (m, 2H), 3.52 (m, 2H), 4.02 (t, 2H), 4.60 (br s, 2H), 6.88 (d, 2H), 7.14 (d, 2H), 7.41 (m, 8H), 7.91 (t, 1H), 8.93 (m, 2H), 9.33 (t, 1H), 10.55 (s, 1H). mp 223-230. m/z (ESI)=463 [C19H27ClN10O2+H]+.

1. additionAfter the addition
2. customthe cooling bath was removed
3. additionAn additional 15 mL of 12N HCl was added dropwise at room temperature
4. waitafter 2 h
5. customreaction completion
6. customThe solvent was evaporated
7. additionmethanol (100 mL) was added
8. customevaporated below 30° C.
9. waitthe residue was placed under vacuum at 40° C. for 2 days