Hydrochloric Acid → cis(+/-)-4-Chloro-N-[3-ethoxy-1-(5-methyl-6-oxo-5,6-dihydro-4H-pyrrolo[3,4-d][1,3]thiazol-2-yl)piperidin-4-yl]-5-ethyl-1H-imidazole-2-carboxamide

HRID 43961Notes

Reaction equation

HRID 43961 reaction equation
C[Al](C)C.[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][N:19]([C:22]3[S:23][C:24]([C:30]([O:32]CC)=O)=[C:25]([CH2:27][NH:28][CH3:29])[N:26]=3)[CH2:18][C@H:17]2[O:35][CH2:36][CH3:37])=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12].Cl>C1(C)C=CC=CC=1>[Cl:5][C:6]1[N:7]=[C:8]([C:13]([NH:15][C@H:16]2[CH2:21][CH2:20][N:19]([C:22]3[S:23][C:24]4[C:30](=[O:32])[N:28]([CH3:29])[CH2:27][C:25]=4[N:26]=3)[CH2:18][C@H:17]2[O:35][CH2:36][CH3:37])=[O:14])[NH:9][C:10]=1[CH2:11][CH3:12]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 16682925TrimethylaluminumHCID 86648842Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-[(methylamino)methyl]-1,3-thiazole-5-carboxylate

Product 1

HCID 86648843cis(+/-)-4-Chloro-N-[3-ethoxy-1-(5-methyl-6-oxo-5,6-dihydro-4H-pyrrolo[3,4-d][1,3]thiazol-2-yl)piperidin-4-yl]-5-ethyl-1H-imidazole-2-carboxamideYield 35%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Trimethylaluminum (1.05 M solution in hexane) (0.76 mL, 0.80 mmol) was added to a solution of ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-[(methylamino)methyl]-1,3-thiazole-5-carboxylate obtained in Example (256a) (80 mg, 0.16 mmol) in toluene (3 mL), and the mixture was heated under reflux for 45 minutes. A 1 N aqueous hydrochloric acid solution was added to the reaction solution, followed by stirring. Then, the mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=20/1) to obtain 25 mg of the title compound as a pale yellow solid (35%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 45 minutes
  3. extractionThen, the mixture was extracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=20/1)

Sources & evidence

ORD record
ord-b18051db88054fe8b74e20c029cd30a5
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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