4-Methylmorpholine → Ethyl 2-(3-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}azetidin-1-yl)-1,3-thiazole-5-carboxylate

HRID 43874Notes

Reaction equation

HRID 43874 reaction equation
CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:30][CH:31]1[CH2:34][N:33]([C:35]2[S:36][C:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:38][N:39]=2)[CH2:32]1.[Cl:45][C:46]1[N:47]=[C:48]([C:53](O)=[O:54])[NH:49][C:50]=1[CH2:51][CH3:52]>CC(N(C)C)=O.ClCCl.C(OCC)(=O)C>[Cl:45][C:46]1[N:47]=[C:48]([C:53]([NH:30][CH:31]2[CH2:34][N:33]([C:35]3[S:36][C:37]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:38][N:39]=3)[CH2:32]2)=[O:54])[NH:49][C:50]=1[CH2:51][CH3:52]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67548752Ethyl 2-(3-aminoazetidin-1-yl)-1,3-thiazole-5-carboxylateHCID 675489294-chloro-5-ethyl-1H-imidazole-2-carboxylic acid

Product 1

HCID 67548970Ethyl 2-(3-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}azetidin-1-yl)-1,3-thiazole-5-carboxylateYield 64%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 85741463dichloromethane N,N-dimethylacetamideSolvent

Procedure

WSC hydrochloride (62 mg, 0.32 mmol), 1-hydroxybenzotriazole (36 mg, 0.27 mmol) and N-methylmorpholine (0.06 mL, 0.54 mmol) were added to a mixed solution of ethyl 2-(3-aminoazetidin-1-yl)-1,3-thiazole-5-carboxylate obtained in Example (217b) (61 mg, 0.27 mmol) and 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained in Example (1d) (47 mg, 0.27 mmol) in DMA/dichloromethane (2 mL/2 mL), and the mixture was stirred at room temperature for 19 hours. The reaction solution was diluted with ethyl acetate, and then the mixture was washed with brine and dried over anhydrous magnesium sulfate. Following filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=20/1) to obtain 66 mg of the title compound as a white solid (64%).

Workup

  1. washthe mixture was washed with brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltration
  4. customthe solvent was evaporated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=20/1)

Sources & evidence

ORD record
ord-e31b73c0a8cf46a081abd3ea44213e4e
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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