Hydrochloric Acid → Ethyl cis(+/-)-(2E)-4-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-oxo-2-butenoate

HRID 43748Notes

Reaction equation

HRID 43748 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20]C(C)(C)C)=O)[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].Cl.C(OCC)(=O)C.[CH2:34]([O:36][C:37](=[O:43])/[CH:38]=[CH:39]/C(O)=O)[CH3:35].CCN=C=NCCCN(C)C.Cl.Cl>CO.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18](=[O:20])/[CH:39]=[CH:38]/[C:37]([O:36][CH2:34][CH3:35])=[O:43])[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5358902Monoethyl fumarateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86648452tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

Product 1

HCID 86648693Ethyl cis(+/-)-(2E)-4-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-oxo-2-butenoate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

tert-Butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained by the method described in Example (1g) (133 mg, 0.34 mmol) was dissolved in methanol (2 mL). A 4 N hydrochloric acid/ethyl acetate solution (4 mL) was added, and the mixture was stirred at 70° C. for 30 minutes. Following concentration under reduced pressure, the residue was dissolved in DMA (5 mL). Fumaric acid monoethyl ester (54.42 mg, 0.38 mmol), WSC hydrochloride (197.41 mg, 1.03 mmol) and DMAP (41.94 mg, 0.34 mmol) were added, and the mixture was stirred at room temperature overnight. Dilute hydrochloric acid was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and dried over anhydrous sodium sulfate.

Workup

  1. concentrationconcentration under reduced pressure
  2. dissolutionthe residue was dissolved in DMA (5 mL)
  3. stirringthe mixture was stirred at room temperature overnight
  4. extractionfollowed by extraction with ethyl acetate
  5. washThen, the organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-e15ae95e59c74b61ae144f731a006476
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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