4-Methylmorpholine → Ethyl 2-{(1R,5R)-2-[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]-2,6-diazabicyclo[3.2.0]hept-6-yl}-4-methyl-1,3-thiazole-5-carboxylate

HRID 43925Notes

Reaction equation

HRID 43925 reaction equation
CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[C@@H:30]12[CH2:36][N:35]([C:37]3[S:38][C:39]([C:43]([O:45][CH2:46][CH3:47])=[O:44])=[C:40]([CH3:42])[N:41]=3)[C@@H:34]1[CH2:33][CH2:32][NH:31]2.[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]([N:31]2[CH2:32][CH2:33][C@@H:34]3[C@H:30]2[CH2:36][N:35]3[C:37]2[S:38][C:39]([C:43]([O:45][CH2:46][CH3:47])=[O:44])=[C:40]([CH3:42])[N:41]=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 67549645Ethyl 2-[(1R,5R)-2,6-diazabicyclo[3.2.0]hept-6-yl]-4-methyl-1,3-thiazole-5-carboxylate

Product 1

HCID 67549834Ethyl 2-{(1R,5R)-2-[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]-2,6-diazabicyclo[3.2.0]hept-6-yl}-4-methyl-1,3-thiazole-5-carboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 85741463dichloromethane N,N-dimethylacetamideSolvent

Procedure

WSC hydrochloride (377 mg, 1.97 mmol), 1-hydroxybenzotriazole (97 mg, 0.72 mmol) and N-methylmorpholine (0.14 mL, 1.31 mmol) were added to a mixed solution of ethyl 2-[(1R,5R)-2,6-diazabicyclo[3.2.0]hept-6-yl]-4-methyl-1,3-thiazole-5-carboxylate obtained in Example (236c) (175 mg, 0.66 mmol) and 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained in Example (1d) (137 mg, 0.79 mmol) in DMA/dichloromethane (4 mL/4 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 5% 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 192 mg of the title compound as a milk white solid (69%).

Workup

  1. washthe mixture was washed with 5% 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-9109fc2b638e4abdb71ef9b050a1cc38
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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