Hydrochloric Acid → Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-1,3-benzothiazole-7-carboxylate

HRID 1424901Notes

Reaction equation

HRID 1424901 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](OC(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.C(N(C(C)C)CC)(C)C.BrC1[S:45][C:46]2[C:52]([C:53]([O:55][CH2:56][CH3:57])=[O:54])=[CH:51][CH:50]=[CH:49][C:47]=2[N:48]=1.Cl>CO>[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]3[S:45][C:46]4[C:52]([C:53]([O:55][CH2:56][CH3:57])=[O:54])=[CH:51][CH:50]=[CH:49][C:47]=4[N:48]=3)[CH2:14][C@H:13]2[O:25][CH3:26])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 21866389Hydrogen chloride-ethyl acetateHCID 67073467Ethyl 2-bromobenzo[d]thiazole-7-carboxylateHCID 86648452tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

Product 1

HCID 86648453Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-1,3-benzothiazole-7-carboxylateYield 65.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained in Example (1g) (117 mg, 0.30 mmol) was dissolved in methanol (2 mL). A 4 N hydrochloric acid/ethyl acetate solution (5 mL) was added, and the mixture was stirred at room temperature for one hour. Following concentration under reduced pressure, the residue was dissolved in DMF (3 mL). Diisopropylethylamine (0.32 mL, 1.84 mmol) and ethyl 2-bromo-1,3-benzothiazole-7-carboxylate obtained in Example (1f) (87 mg, 0.30 mmol) were added, and the mixture was stirred at 70° C. for two hours. Dilute hydrochloric acid was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=5/1, ethyl acetate) to obtain 97 mg of the title compound as a pale yellow solid (65%).

Workup

  1. concentrationconcentration under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (3 mL)
  3. stirringthe mixture was stirred at 70° C. for two hours
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentration under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=5/1, ethyl acetate)

Sources & evidence

ORD record
ord-201a54bcfc084232b1515a4b1247a5fa
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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