Ethyl bromoacetate → 1-Ethoxycarbonylmethyl-3-(pyridin-4-ylamino)-1H-indole-2-carboxylic Acid Ethyl Ester

HRID 1376118Notes

Reaction equation

HRID 1376118 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]([O:19][CH2:20][CH3:21])=[O:18])=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].O1CCCC1.Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>CN(C)C=O>[CH2:20]([O:19][C:17]([C:9]1[N:10]([CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[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:18])[CH3:21]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 8028TetrahydrofuranHCID 104689203-(4-Pyridinylamino)-1H-indole-2-carboxylic acid ethyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 587884181-Ethoxycarbonylmethyl-3-(pyridin-4-ylamino)-1H-indole-2-carboxylic Acid Ethyl EsterYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Under nitrogen, stir and cool to 0° C. a mixture of ethyl 3-(4-pyridinylamino)indole-2-carboxylate (see U.S. Pat. No. 5,328,920; 0.20 g, 0.711 mmol) in dimethylformamide (5 mL). Add a 1M solution of potassium tert-butoxide in tetrahydrofuran (0.75 mL, 0.75 mmol) in one portion, stir for 10 min, and then add ethyl bromoacetate (0.12 g, 0.72 mmol) in one portion. Stir at 0° C. for 50 min and quench the reaction into water (30 mL). Extract the aqueous mixture with ethyl acetate (2×20 mL), combine the extracts, wash with water (25 mL), brine (25 mL) and dry over MgSO4. Concentrate under vacuum, chromatograph the residue on a Redisep silica gel cartridge (10 g) eluting with 5% methanol/dichloromethane to 20% methanol/dichloromethane. Combine non-homogeneous fractions concentrate and chromatograph again as above. Combine all homogenous fractions and concentrate to obtain 0.13 g (50%) of the title compound as a white solid: MS 368(M+H).

Workup

  1. stirringstir for 10 min
  2. stirringStir at 0° C. for 50 min
  3. customquench
  4. customthe reaction into water (30 mL)
  5. extractionExtract the aqueous mixture with ethyl acetate (2×20 mL)
  6. washwash with water (25 mL), brine (25 mL)
  7. dry with materialdry over MgSO4
  8. concentrationConcentrate under vacuum, chromatograph the residue on a Redisep silica gel cartridge (10 g)
  9. washeluting with 5% methanol/dichloromethane to 20% methanol/dichloromethane
  10. concentrationCombine non-homogeneous fractions concentrate
  11. concentrationCombine all homogenous fractions and concentrate

Sources & evidence

ORD record
ord-56a0813cf1914e17909f7a7b04d792aa
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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