Ethyl Acetate → 3-(Pyridin-4-ylamino)-1H-indole-2-carboxylic Acid Diethylcarbamoylmethyl Ester

HRID 1376124Notes

Reaction equation

HRID 1376124 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([OH:19])=[O:18])=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:27][C:28]([N:30]([CH2:33][CH3:34])[CH2:31][CH3:32])=[O:29].CCOC(C)=O>CN(C=O)C.[Cl-].[Na+].O.CO.CCOC(C)=O>[CH2:31]([N:30]([CH2:33][CH3:34])[C:28]([CH2:27][O:18][C:17]([C:9]1[NH:10][C:11]2[C:16]([C:8]=1[NH:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:19])=[O:29])[CH3:32]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 16844Chloro-N,N-diethylacetamideHCID 101989283-(pyridin-4-ylamino)-1H-indole-2-carboxylic Acid

Product 1

HCID 103615393-(Pyridin-4-ylamino)-1H-indole-2-carboxylic Acid Diethylcarbamoylmethyl EsterYield 96.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 21584119Ethylacetate methanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

Stir at 50° C. for 10 min. a mixture of 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid (2.0 g, 8 mmol), KI (10 mg) and Cs2CO3 (2.8 g, 8.6 mmol) in DMF (125 mL). Allow to cool to ambient temperature and then cool in an ice bath. Add 2-chloro-N,N-diethylacetamide (1.077 g, 0.9 mmol) and allow to warm to ambient temperature. Add a brine solution to the reaction and extract with EtOAc (3×). Wash the extract with brine and water, dry (MgSO4), filter and concentrate under vacuum to give a semi-solid. Flash chromatograph over silica gel eluting first with EtOAc and 10% MeOH/EtOAc and obtain 0.317 g the title compound as a solid: MS 367(M+H); HPLC: Rt=4.75 min. (95/5/0.1 (A) 5/95/0.1 (B) Water/CAN/Formic Acid YMC ODS-A 2×50 mm 1 mL/min Gradient Composition: 100% A for 0.1 min Linear Gradient to 100% B at 2 min Hold until 3.5 min).

Workup

  1. temperatureAllow to cool to ambient temperature
  2. temperaturecool in an ice bath
  3. temperatureto warm to ambient temperature
  4. customto the reaction
  5. extractionextract with EtOAc (3×)
  6. washWash the
  7. extractionextract with brine and water
  8. dry with materialdry (MgSO4)
  9. filtrationfilter
  10. concentrationconcentrate under vacuum
  11. customto give a semi-solid

Sources & evidence

ORD record
ord-7a4bfb7204e64285affe38407a3652ec
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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