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

HRID 43884Notes

Reaction equation

HRID 43884 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:43]([O:45][CH2:46][CH3:47])=[O:44])=[C:38]([CH:40]([CH3:42])[CH3:41])[N:39]=2)[CH2:32]1.[Cl:48][C:49]1[N:50]=[C:51]([C:56](O)=[O:57])[NH:52][C:53]=1[CH2:54][CH3:55]>CC(N(C)C)=O.ClCCl.C(OCC)(=O)C>[Cl:48][C:49]1[N:50]=[C:51]([C:56]([NH:30][CH:31]2[CH2:34][N:33]([C:35]3[S:36][C:37]([C:43]([O:45][CH2:46][CH3:47])=[O:44])=[C:38]([CH:40]([CH3:42])[CH3:41])[N:39]=3)[CH2:32]2)=[O:57])[NH:52][C:53]=1[CH2:54][CH3:55]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 675489294-chloro-5-ethyl-1H-imidazole-2-carboxylic acidHCID 67548973Ethyl 2-(3-aminoazetidin-1-yl)-4-isopropyl-1,3-thiazole-5-carboxylate

Product 1

HCID 67548784Ethyl 2-(3-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}azetidin-1-yl)-4-isopropyl-1,3-thiazole-5-carboxylateYield 41%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 85741463dichloromethane N,N-dimethylacetamideSolvent

Procedure

WSC hydrochloride (203 mg, 1.06 mmol), 1-hydroxybenzotriazole (48 mg, 0.35 mmol) and N-methylmorpholine (0.08 mL, 0.71 mmol) were added to a mixed solution of ethyl 2-(3-aminoazetidin-1-yl)-4-isopropyl-1,3-thiazole-5-carboxylate obtained in Example (221b) (95 mg, 0.35 mmol) and 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained in Example (1d) (62 mg, 0.35 mmol) in DMA/dichloromethane (4 mL/2 mL), and the mixture was stirred at room temperature for 14 hours. The reaction solution was diluted with ethyl acetate, and then the mixture was washed with 10% saline 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: hexane/ethyl acetate=2/1) to obtain 61 mg of the title compound as a white solid (41%).

Workup

  1. washthe mixture was washed with 10% saline
  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: hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-a5a897ca62c5459fa5f4c48880466478
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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