Hydrochloric Acid → cis(+/-)-2-[4-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-2-oxopyridin-1(2H)-yl]-4-methyl-1,3-thiazole-5-carboxylic acid

HRID 43729Notes

Reaction equation

HRID 43729 reaction equation
[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]3[CH:23]=[CH:22][N:21]([C:24]4[S:25][C:26]([C:30]([O:32]CC)=[O:31])=[C:27]([CH3:29])[N:28]=4)[C:20](=[O:35])[CH:19]=3)[CH2:14][C@H:13]2[O:36][CH2:37][CH3:38])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].[OH-].[Na+].Cl>O1CCOCC1.[Cl-].[Na+].O>[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]3[CH:23]=[CH:22][N:21]([C:24]4[S:25][C:26]([C:30]([OH:32])=[O:31])=[C:27]([CH3:29])[N:28]=4)[C:20](=[O:35])[CH:19]=3)[CH2:14][C@H:13]2[O:36][CH2:37][CH3:38])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86648677Ethyl cis(+/-)-2-[4-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-2-oxopyridin-1(2H)-yl]-4-methyl-1,3-thiazole-5-carboxylate

Product 1

HCID 86648678cis(+/-)-2-[4-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-2-oxopyridin-1(2H)-yl]-4-methyl-1,3-thiazole-5-carboxylic acidYield 44%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Ethyl cis(±)-2-[4-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-2-oxopyridin-1(2H)-yl]-4-methyl-1,3-thiazole-5-carboxylate obtained in Example (140b) (10.8 mg, 0.0192 mmol) was dissolved in dioxane (0.5 mL). A 1 N aqueous sodium hydroxide solution (0.5 ml, 0.5 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction solution was neutralized with 1 N hydrochloric acid and brine was added, followed by extraction with chloroform three times. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Thereafter, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=9/1) to obtain 4.5 mg of the title compound as a colorless solid (44%).

Workup

  1. additionwas added
  2. extractionfollowed by extraction with chloroform three times
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThereafter, the residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=9/1)

Sources & evidence

ORD record
ord-bd66cf8021cc43f6a2a487db7304a2de
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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