反应详情

10.5 g (0.063 mole) of methyl 3-methoxypicolinate and 17.6 g (0.137 mole) of 1-ethyl-2-(aminomethyl)-pyrrolidine are heated under nitrogen for 6 hours to 80° C. The excess base is distilled off in a high vacuum at 50° C and the oily residue is dissolved in methylene chloride and treated with 12 ml of 6 N ethanolic hydrochloric acid. The solvent is evaporated in vacuo and the oily residue is crystallised by trituration with ether. The crystals are collected by filtration and recrystallised from isopropanol-ethyl acetate to yield crude N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride. The combined mother solutions are concentrated in vacuo and the free base is recovered as solution with 2 N sodium hydroxide solution and methylene chloride. The solution is concentrated, the residue dissolved in chloroform and chromatographed through a column of 60 g of silica gel with chloroform-methanol (98:2) as eluant. The base so obtained is again converted with ethanolic hydrochloric acid into the hydrochloride, which is recrystallised from ether. The combined crude hydrochlorides are recrystallised from isopropanol-ethyl acetate and yield pure N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride with a melting point of 162°-163° C.

1. distillationThe excess base is distilled off in a high vacuum at 50° C
2. dissolutionthe oily residue is dissolved in methylene chloride
3. additiontreated with 12 ml of 6 N ethanolic hydrochloric acid
4. customThe solvent is evaporated in vacuo
5. customthe oily residue is crystallised by trituration with ether
6. filtrationThe crystals are collected by filtration
7. customrecrystallised from isopropanol-ethyl acetate
8. customto yield crude N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride
9. concentrationThe combined mother solutions are concentrated in vacuo
10. customthe free base is recovered as solution with 2 N sodium hydroxide solution and methylene chloride
11. concentrationThe solution is concentrated
12. dissolutionthe residue dissolved in chloroform
13. customchromatographed through a column of 60 g of silica gel with chloroform-methanol (98:2) as eluant
14. customThe base so obtained
15. customis recrystallised from ether
16. customare recrystallised from isopropanol-ethyl acetate