Sodium Hydroxide → HCID 21914127, compound

HRID 551408Notes

Reaction equation

HRID 551408 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH:5]1[C:13]1[N:17]=[C:16]([CH2:18][CH2:19][CH3:20])[NH:15][N:14]=1)(=O)C.[OH-].[Na+]>C(O)C.C(OCC)(=O)C>[CH2:18]([C:16]1[NH:15][N:14]=[C:13]([CH:5]2[CH2:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[NH:4]2)[N:17]=1)[CH2:19][CH3:20]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 21914092HCID 21914092, compound

Product 1

HCID 21914127HCID 21914127, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the compound 91 (0.42 g) in ethanol (25 ml) was treated with an aqueous NaOH solution (3 M, 25 mL) and the reaction mix was refluxed for 24 hours. The reaction was cooled, diluted with ethyl acetate, and treated with cold distilled water. The layers were separated and the aqueous fraction was extracted 5 times with ethyl acetate and the combined organic fractions were dried, concentrated and purified by preparatory column chromatography yielding 2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole. b) A solution of 2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole (0.00017 mole) in DCM (5 ml) was treated with N-ethyl-N-(1-methylethyl)-2-propanamine (0.00072 mole) then (2-fluoro-2-oxoethyl)-9H-fluoren-9-yl-carbamic acid methyl ester (0.00070 mole). The reaction was stirred at room temperature for 15 hours. The reaction was diluted with DCM, treated twice with saturated NaHCO3, and dried over Na2SO4 and concentrated. The residue was subjected to reverse phase prep column chromatography to obtain 0.02 g of the desired mono-adduct and 0.02 g of a bis-adduct that was completely converted to the desired mono-adduct by treatment with the prep chromatography eluent (0.1% trifluoroacetic acid in water/acetonitrile). These were combined, yielding 0.03 g of H-fluoren-9-ylmethyl[2-[2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indol-1-yl]-2-oxoethyl]-carbamate. c) A solution of H-fluoren-9-ylmethyl[2-[2,3-dihydro-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indol-1-yl]-2-oxoethyl]-carbamate (0.00006 mole) in DCM (10 ml) was treated with piperidine (0.010 mole) and stirred at room temperature for 1 hour. The completed reaction was concentrated in vacuo and subjected to reverse phase prep column chromatography, yielding 0.02 g of 2,3-dihydro-β-oxo-2-(5-propyl-1H-1,2,4-triazol-3-yl)-1H-indole-1-ethanamine trifluoroacetate (1:1) (compound 92).

Workup

  1. additionthe reaction mix
  2. temperaturewas refluxed for 24 hours
  3. temperatureThe reaction was cooled
  4. additiontreated
  5. distillationwith cold distilled water
  6. customThe layers were separated
  7. extractionthe aqueous fraction was extracted 5 times with ethyl acetate
  8. customthe combined organic fractions were dried
  9. concentrationconcentrated
  10. custompurified by preparatory column chromatography

Sources & evidence

ORD record
ord-4b7b2230b6934f738a12c453887ae728
Source dataset
uspto-grants-2011_05
Patent number
US07947713B2

Reaction notes

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