Hydrochloric Acid → 3-({[4-({Cyclohexyl[5-(cyclohexylcarbonyl)-2-ethylthiophen-3-yl]methyl}amino)phenyl]carbonyl}amino)propanoic acid

HRID 1877269Notes

Reaction equation

HRID 1877269 reaction equation
[CH:1]1([CH:7]([NH:23][C:24]2[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=2)[C:8]2[CH:12]=[C:11]([C:13]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[O:14])[S:10][C:9]=2[CH2:21][CH3:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:34][CH2:35][CH2:36][C:37]([O:39]CC)=[O:38].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[OH-].[Na+]>CN(C)C=O.C(O)C.O1CCCC1.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([C:28]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:29])=[CH:31][CH:32]=2)[C:8]2[CH:12]=[C:11]([C:13]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)=[O:14])[S:10][C:9]=2[CH2:21][CH3:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 685165864-({Cyclohexyl[5-(cyclohexylcarbonyl)-2-ethylthiophen-3-yl]methyl}amino)benzoic acid

Product 1

HCID 595293113-({[4-({Cyclohexyl[5-(cyclohexylcarbonyl)-2-ethylthiophen-3-yl]methyl}amino)phenyl]carbonyl}amino)propanoic acidYield 83.1%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 4-({cyclohexyl[5-(cyclohexylcarbonyl)-2-ethylthiophen-3-yl]methyl}amino)benzoic acid (130 mg) synthesized above, ethyl β-alaninate hydrochloride (66.2 mg), 1-hydroxybenzotriazole monohydrate (66.0 mg) and triethylamine (60 μL) in N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (82.6 mg), and the mixture was stirred at room temperature overnight. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50% ethyl acetate/hexane) to give colorless oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (1 mL), and the mixture was stirred at room temperature for 5 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (1 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title compound (125 mg, 83%) as a white solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (50% ethyl acetate/hexane)
  8. customto give colorless oil
  9. stirringthe mixture was stirred at room temperature for 5 hr
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue was dissolved in water (10 mL)
  12. addition1N hydrochloric acid (1 mL) was added at 0° C
  13. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-569d46d468c74d30b266f4b4426f99c7
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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