Hydrochloric Acid → HCID 59529473, compound

HRID 1877220Notes

Reaction equation

HRID 1877220 reaction equation
[CH:1]1([CH:7]([NH:15][C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][CH:17]=2)[C:8]2[CH:12]=[C:11]([CH3:13])[S:10][C:9]=2[CH3:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:25][NH:26][CH2:27][CH2:28][C:29]([O:31]CC)=[O:30].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:15][C:16]2[CH:17]=[CH:18][C:19]([C:20]([N:26]([CH3:25])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:22])=[CH:23][CH:24]=2)[C:8]2[CH:12]=[C:11]([CH3:13])[S:10][C:9]=2[CH3:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 541480Ethyl 3-(methylamino)propanoateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68511333HCID 68511333, compound

Product 1

HCID 59529473HCID 59529473, compoundYield 5%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 4-{[cyclohexyl(2,5-dimethylthiophen-3-yl)methyl]amino}benzoic acid (250 mg) synthesized in Example 270 (4), ethyl 3-(methylamino)propanoate (115 mg), 1-hydroxybenzotriazole monohydrate (134 mg) and triethylamine (122 μL) in N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (168 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 NH-silica gel column chromatography (ethyl acetate) to give a 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 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 a white solid. The obtained solid was purified by silica gel column chromatography (60% ethyl acetate/hexane) to give colorless oil. The obtained oil was crystallized from hexane to give the title compound (15.4 mg, 5%) 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 NH-silica gel column chromatography (ethyl acetate)
  8. customto give a colorless 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
  14. customto give a white solid
  15. customThe obtained solid was purified by silica gel column chromatography (60% ethyl acetate/hexane)
  16. customto give colorless oil
  17. customThe obtained oil was crystallized from hexane

Sources & evidence

ORD record
ord-b004578519db4573ad08020e6bed15ce
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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