Hydrochloric Acid → Ethyl cis(+/-)-2-{3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidin-1-yl}-1,3-thiazole-5-carboxylate

HRID 43557

反応式

HRID 43557 の反応式
Cl.C(OCC)(=O)C.[CH2:8]([O:15][C@H:16]1[C@@H:21]([NH:22][C:23]([C:25]2[NH:26][CH:27]=[CH:28][N:29]=2)=[O:24])[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(N(C(C)C)CC)(C)C.Br[C:47]1[S:48][C:49]([C:52]([O:54][CH2:55][CH3:56])=[O:53])=[CH:50][N:51]=1.Cl>>[CH2:8]([O:15][C@H:16]1[C@@H:21]([NH:22][C:23]([C:25]2[NH:26][CH:27]=[CH:28][N:29]=2)=[O:24])[CH2:20][CH2:19][N:18]([C:47]2[S:48][C:49]([C:52]([O:54][CH2:55][CH3:56])=[O:53])=[CH:50][N:51]=2)[CH2:17]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

参加物

6

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 3614103Ethyl 2-bromothiazole-5-carboxylateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86648572tert-Butyl cis(+/-)-3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidine-1-carboxylate

生成物 1

HCID 86648573Ethyl cis(+/-)-2-{3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidin-1-yl}-1,3-thiazole-5-carboxylate収率 76.1%

実験手順

A 4 N hydrochloric acid/ethyl acetate solution (10 mL, 40 mmol) was added to tert-butyl cis(±)-3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidine-1-carboxylate obtained in Example (90e) (0.3 g, 0.75 mmol), and the mixture was stirred at room temperature for 20 minutes. Following concentration under reduced pressure, the residue was dissolved in DMF (8 mL). Diisopropylethylamine (0.45 g, 3.5 mmol) and ethyl 2-bromo-1,3-thiazole-5-carboxylate (0.21 g, 0.9 mmol) were added, and the mixture was stirred at 70° C. for 1.5 hours. Dilute hydrochloric acid was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous sodium magnesium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=5/1, ethyl acetate) to obtain 0.26 g of the title compound as a light brown solid (76%).

後処理

  1. concentrationconcentration under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (8 mL)
  3. stirringthe mixture was stirred at 70° C. for 1.5 hours
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialdried over anhydrous sodium magnesium sulfate
  7. concentrationconcentration under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=5/1, ethyl acetate)

出典と根拠

ORDレコード
ord-5a350d06ab9c4ca1928623adbc868163
出典データセット
uspto-grants-2013_09
特許番号
US08536197B2

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