Ethylamine → Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-(ethylcarbamoyl)-1,3-thiazole-5-carboxylate

HRID 43949

Reaction equation

HRID 43949 reaction equation
[CH2:1]([NH2:3])[CH3:2].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.[Cl:26][C:27]1[N:28]=[C:29]([C:34]([NH:36][C@H:37]2[CH2:42][CH2:41][N:40]([C:43]3[S:44][C:45]([C:51]([O:53][CH2:54][CH3:55])=[O:52])=[C:46]([C:48]([OH:50])=O)[N:47]=3)[CH2:39][C@H:38]2[O:56][CH2:57][CH3:58])=[O:35])[NH:30][C:31]=1[CH2:32][CH3:33]>CC(N(C)C)=O.ClCCl.C(OCC)(=O)C>[Cl:26][C:27]1[N:28]=[C:29]([C:34]([NH:36][C@H:37]2[CH2:42][CH2:41][N:40]([C:43]3[S:44][C:45]([C:51]([O:53][CH2:54][CH3:55])=[O:52])=[C:46]([C:48](=[O:50])[NH:3][CH2:1][CH3:2])[N:47]=3)[CH2:39][C@H:38]2[O:56][CH2:57][CH3:58])=[O:35])[NH:30][C:31]=1[CH2:32][CH3:33]

Participants

7

Reactant 4

HCID 6341EthylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86648529cis(+/-)-2-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-5-(ethoxycarbonyl)-1,3-thiazole-4-carboxylic acid

Product 1

HCID 86648833Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-(ethylcarbamoyl)-1,3-thiazole-5-carboxylateYield 81.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 85741463dichloromethane N,N-dimethylacetamideSolvent

Procedure

Ethylamine (2.0 M solution in THF) (0.60 mL, 1.20 mmol), WSC hydrochloride (345 mg, 1.80 mmol) and 1-hydroxybenzotriazole (8 1 mg, 0.60 mmol) were added to a mixed solution of cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-5-(ethoxycarbonyl)-1,3-thiazole-4-carboxylic acid obtained in Example (50a) (300 mg, 0.60 mmol) in DMA/dichloromethane (6 mL/6 mL) at room temperature, followed by stirring for five hours. The reaction solution was diluted with ethyl acetate, and then the mixture was washed with a 1 N aqueous hydrochloric acid solution and 5% saline. The organic layer was dried over anhydrous magnesium sulfate. Following filtration, the filtrate was concentrated under reduced pressure. The resulting residue was suspended and washed in diethyl ether to obtain 257 mg of the title compound as a white solid (81%).

Workup

  1. washthe mixture was washed with a 1 N aqueous hydrochloric acid solution and 5% saline
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. washwashed in diethyl ether

Sources & evidence

ORD record
ord-9709f6803c124b358681070d3a0289e4
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Linked notes

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