反应详情

To a solution of 2-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}ethylamine (example 437B, 230 mg) in acetonitrile (15 mL) is added is added N,N′-bis-Boc-guanylpyrazole (172 mg) and diisopropylethylamine (1 equivalent) at room temperature. The mixture is stirred at room temperature for 3 h. The solvent and volatiles are removed under reduced pressure. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol from 100/0 to 95/5). The residue is then dissolved in 5N aqueous hydrochloric acid (8 mL) and the solution is stirred overnight at room temperature. The solvent and volatiles are removed under reduced pressure and the residue is triturated with diethyl ether and filtered to afford N-(2-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}ethyl) guanidine trihydrochlorhide as a white crystalline solid melting at 170° C.

1. customThe solvent and volatiles are removed under reduced pressure
2. customThe residue is purified by chromatography on silica gel (gradient dichloromethane/methanol from 100/0 to 95/5)
3. dissolutionThe residue is then dissolved in 5N aqueous hydrochloric acid (8 mL)
4. stirringthe solution is stirred overnight at room temperature
5. customThe solvent and volatiles are removed under reduced pressure
6. customthe residue is triturated with diethyl ether
7. filtrationfiltered