Hydrochloric Acid → HCID 66778111, compound

HRID 2090978Notes

Reaction equation

HRID 2090978 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH:10]([NH:17][C:18]2[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=2)[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:2]1.Cl.C([O:30][C:31](=[O:35])[CH2:32][CH2:33][NH2:34])C.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[OH-].[Na+]>C(O)C.O1CCCC1.CN(C)C=O.C(N(CC)CC)C>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH:10]([NH:17][C:18]2[CH:26]=[CH:25][C:21]([C:22]([NH:34][CH2:33][CH2:32][C:31]([OH:30])=[O:35])=[O:23])=[CH:20][CH:19]=2)[CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]2)=[CH:2]1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66777972HCID 66777972, compound

Product 1

HCID 66778111HCID 66778111, compoundYield 67.3%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 4-{[1-benzothiophen-3-yl(cyclohexyl)methyl]amino}benzoic acid (250 mg) synthesized above, β-alanine ethyl ester hydrochloride (126 mg), 1-hydroxybenzotriazole.monohydrate (126 mg), triethylamine (114 μL) and N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (157 mg), and the mixture was stirred at room temperature for 2 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio) to give a pale-yellow 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 2 hr. The reaction mixture was concentrated under reduced pressure, and 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 object compound (201 mg, 67%) 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 brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio)
  8. customto give a pale-yellow oil
  9. stirringthe mixture was stirred at room temperature for 2 hr
  10. concentrationThe reaction mixture was concentrated 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-89378802077a499db08d175864666d47
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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