Hydrochloric Acid → 2-{(3S,4R)-4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidin-1-yl}-1,3-benzothiazole-7-carboxylic acid

HRID 43852Notes

Reaction equation

HRID 43852 reaction equation
[OH-].[Li+].[Cl:3][C:4]1[N:5]=[C:6]([C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][N:17]([C:20]3[S:21][C:22]4[C:28]([C:29]([O:31]CC)=[O:30])=[CH:27][CH:26]=[CH:25][C:23]=4[N:24]=3)[CH2:16][C@@H:15]2[NH:34][CH:35]([CH2:38][CH3:39])[CH2:36][CH3:37])=[O:12])[NH:7][C:8]=1[CH2:9][CH3:10].Cl>CO.O1CCCC1>[Cl:3][C:4]1[N:5]=[C:6]([C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][N:17]([C:20]3[S:21][C:22]4[C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=[CH:25][C:23]=4[N:24]=3)[CH2:16][C@@H:15]2[NH:34][CH:35]([CH2:36][CH3:37])[CH2:38][CH3:39])=[O:12])[NH:7][C:8]=1[CH2:9][CH3:10]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 67549801Ethyl 2-{(3S,4R)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidin-1-yl}-1,3-benzothiazole-7-carboxylate

Product 1

HCID 509153162-{(3S,4R)-4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidin-1-yl}-1,3-benzothiazole-7-carboxylic acidYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A 2 N aqueous lithium hydroxide solution (439 μL, 0.877 mmol) was added to a mixed solution of ethyl 2-{(3S,4R)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-[(1-ethylpropyl)amino]piperidin-1-yl}-1,3-benzothiazole-7-carboxylate obtained in Example (202f) (48.0 mg, 0.088 mmol) in methanol (0.3 mL) and tetrahydrofuran (0.3 mL) at room temperature, and the mixture was stirred at 70° C. for two hours. The reaction solution was concentrated under reduced pressure and water was added. The aqueous layer was washed with diethyl ether. A 1 N aqueous hydrochloric acid solution (877 μL, 0.877 mmol) was added to the aqueous layer, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and brine, and dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure to obtain 42 mg of the title compound (92%) as a pale yellow solid.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure and water
  2. additionwas added
  3. washThe aqueous layer was washed with diethyl ether
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe resulting organic layer was washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe insoluble matter was separated by filtration
  8. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-46b8890af94a4b0c9826428698f72551
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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