Diisopropylethylamine → cis(+/-)-4-Chloro-5-ethyl-N-(1-formyl-3-methoxypiperidin-4-yl)-1H-imidazole-2-carboxylic acid amide

HRID 43986ノート

反応式

HRID 43986 の反応式
[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18](OC(C)(C)C)=[O:19])[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].Cl.C(OCC)(=O)C.C(N(C(C)C)CC)(C)C>CO>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([CH:18]=[O:19])[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 21866389Hydrogen chloride-ethyl acetateHCID 86648452tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

生成物 1

HCID 86648867cis(+/-)-4-Chloro-5-ethyl-N-(1-formyl-3-methoxypiperidin-4-yl)-1H-imidazole-2-carboxylic acid amide収率 27%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

tert-Butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained in Example (1g) (30 mg, 0.08 mmol) was dissolved in methanol (0.5 mL). A 4 N hydrochloric acid/ethyl acetate solution (2.5 mL) was added, and the mixture was stirred at room temperature for 4.5 hours. Following concentration under reduced pressure, the residue was dissolved in DMF (2 mL). Diisopropylethylamine (0.054 mL, 0.31 mmol) was added, and the mixture was stirred at 140° C. using a microwave reactor for one hour. Saline was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. Following concentration under reduced pressure, the residue was purified by reverse phase high performance liquid chromatography (Develosil, 2 cm diameter×10 cm, 0.1% formic acid-containing acetonitrile/water mixed solvent) to obtain 6.6 mg of the title compound as a pale yellow solid (27%).

後処理

  1. concentrationconcentration under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (2 mL)
  3. stirringthe mixture was stirred at 140° C.
  4. customfor one hour
  5. additionSaline was added to the reaction solution
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentration under reduced pressure
  10. customthe residue was purified by reverse phase high performance liquid chromatography (Develosil, 2 cm diameter×10 cm, 0.1% formic acid-containing acetonitrile/water mixed solvent)

出典と根拠

ORDレコード
ord-89780092c0e949528a5ae96b44fc9cfd
出典データセット
uspto-grants-2013_09
特許番号
US08536197B2

反応ノート

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