Citric Acid → HCID 57476348, compound

HRID 1994962Notes

Reaction equation

HRID 1994962 reaction equation
[CH3:1][N:2]([S:23]([C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1)(=[O:25])=[O:24])[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18](OCC)=[O:19])[CH2:15][N:16]=1)=[CH:8]2.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.Cl.C[N:49](C)CCCN=C=NCC>O.CN(C)C=O.C(O)C.O1CCCC1>[CH3:1][N:2]([S:23]([C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1)(=[O:24])=[O:25])[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([NH2:49])=[O:19])[CH2:15][N:16]=1)=[CH:8]2

Participants

9

Reactant 4

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59136111HCID 59136111, compound

Product 1

HCID 57476348HCID 57476348, compoundYield 42.1%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of ethyl (2-{7-[methyl(pyridin-3-ylsulfonyl)amino]-1H-indol-2-yl}-4,5-dihydro-1,3-thiazol-5-yl)acetate (330 mg), 1N aqueous sodium hydroxide solution (5 mL), tetrahydrofuran (5 mL) and ethanol (5 mL) was stirred at 50° C. for 30 min. The reaction mixture was acidified with aqueous citric acid solution, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4), and concentrated to give pale-yellow crystals. A mixture of the obtained crystals, 1H-1,2,3-benzotriazol-1-ol-ammonia complex (1.10 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1.38 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 2.5 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography, and eluted with ethyl acetate-methanol (100:0-85:15, volume ratio) to give the title compound (130 mg, yield 42%) as colorless crystals. The crystals were recrystallized from ethyl acetate-hexane to give colorless prism crystals. melting point 185-186° C.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto give pale-yellow crystals
  6. stirringwas stirred at room temperature for 2.5 days
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe ethyl acetate layer was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. washeluted with ethyl acetate-methanol (100:0-85:15, volume ratio)

Sources & evidence

ORD record
ord-bd57d0c15ed14794b012cfab018a8a3a
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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