Sodium Hydroxide → HCID 59529506, compound

HRID 1877206Notes

Reaction equation

HRID 1877206 reaction equation
[CH:1]1([CH:7]([NH:21][C:22]2[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=2)[C:8]2[CH:12]=[C:11]([C:13]3[CH2:14][CH2:15][S:16][CH2:17][CH:18]=3)[S:10][C:9]=2[CH2:19][CH3:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:32][CH2:33][CH2:34][C:35]([O:37]CC)=[O:36].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[Cl-].[NH4+].[OH-].[Na+]>CN(C)C=O.C(O)C.O1CCCC1.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:26]([NH:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[O:27])=[CH:29][CH:30]=2)[C:8]2[CH:12]=[C:11]([C:13]3[CH2:14][CH2:15][S:16][CH2:17][CH:18]=3)[S:10][C:9]=2[CH2:19][CH3:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

11

Reactant 6

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68512089HCID 68512089, compound

Product 1

HCID 59529506HCID 59529506, compoundYield 50.8%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 4-({cyclohexyl[5-(3,6-dihydro-2H-thiopyran-4-yl)-2-ethylthiophen-3-yl]methyl}amino)benzoic acid (246 mg) synthesized above, ethyl β-alaninate hydrochloride (98.8 mg), 1-hydroxybenzotriazole monohydrate (98.5 mg) and triethylamine (90 μL) in N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (123 mg), and the mixture was stirred at room temperature for 8 hr. Saturated aqueous ammonium chloride solution 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 brown 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 2.5 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 (145 mg, 47%) as a brown 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 brown oil
  9. stirringthe mixture was stirred at room temperature for 2.5 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-a93011aff212459791de717b25977496
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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