Hydrochloric Acid → N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride

HRID 372206ノート

反応式

HRID 372206 の反応式
[CH3:1][O:2][C:3]1[C:4]([C:9]([O:11]C)=O)=[N:5][CH:6]=[CH:7][CH:8]=1.[CH2:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH:16]1[CH2:20][NH2:21])[CH3:14].[ClH:22]>>[ClH:22].[CH2:13]([N:15]1[CH2:19][CH2:18][CH2:17][CH:16]1[CH2:20][NH:21][C:9](=[O:11])[C:4]1[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:14]

参加物

4

反応物 3

HCID 313Hydrochloric Acid2 回HCID 1172952-Aminomethyl-1-ethylpyrrolidineHCID 20474189Methyl 3-methoxypyridine-2-carboxylate

生成物 1

HCID 20328813N-[(1-ethyl-2-pyrrolidinyl)-methyl]-3-methoxypicolinamide hydrochloride

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-02c55c0455984864b421f6a6c45b5d3e
出典データセット
uspto-grants-1978_05
特許番号
US04089960

反応ノート

読み込み中…