2-Pyrrolidinone, 1-(chloromethyl)- → 3-(Pyridin-4-ylamino)-1H-indole-2-carboxylic acid 2-oxo-pyrrolidin-1-yl-methyl ester

HRID 1376132Notes

Reaction equation

HRID 1376132 reaction equation
[K+].[N:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[C:18]([O-:20])=[O:19])=[CH:4][CH:3]=1.Cl[CH2:22][N:23]1[CH2:27][CH2:26][CH2:25][C:24]1=[O:28]>C1COCC1>[O:28]=[C:24]1[CH2:25][CH2:26][CH2:27][N:23]1[CH2:22][O:19][C:18]([C:10]1[NH:11][C:12]2[C:17]([C:9]=1[NH:8][C:5]1[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:20]

Participants

4

Reactant 2

HCID 27704972-Pyrrolidinone, 1-(chloromethyl)-HCID 69006665HCID 69006665, compound

Product 1

HCID 103605033-(Pyridin-4-ylamino)-1H-indole-2-carboxylic acid 2-oxo-pyrrolidin-1-yl-methyl esterYield 8.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Heated at 50° C. a suspension of 3-(4-pyridinylamino)-1H-indole-2-carboxylic acid potassium salt (2.0 g, 6.86 mmol) in anhydrous THF (100 mL) was oil bath for 20 min. Add to it a solution of N-(chloromethyl)-2-pyrrolidinone (1.10 g, 8.23 mmol) in anhydrous THF (5 mL) dropwise. After 3 hrs, cool the reaction to ambient temperature. Add water (100 mL) and extract with ethyl acetate (3×100 mL). Combine the organic layers and wash with NaHCO3 (sat), water, brine, dry with MgSO4 and then concentrate. Purify the residue on an ISCO RediSep 10-gram silicagel cartridge, eluting with ethyl acetate and then 5% methanol in ethyl acetate. Combine product containing fractions and concentrate to give the title compound as an off-yellow solid (205 mg): MS 313(M+H), TLC (silica gel, MeOH/EtOAc 1:1). Rf=0.33, 1H NMR (DMSO-d6) δ 11.78 (1H, s), 8.47 (1H, s), 8.09 (2H, d, J=6.2 Hz), 7.49 (3H, m), 7.09 (1H, m), 6.59 (2H), 5.76 (residual CH2Cl2), 5.44 (2H, s), 3.37 (2H, m), 2.22 (2H, m), 1.87 (2H, m).

Workup

  1. customfor 20 min
  2. temperaturecool
  3. customthe reaction to ambient temperature
  4. extractionAdd water (100 mL) and extract with ethyl acetate (3×100 mL)
  5. washCombine the organic layers and wash with NaHCO3 (sat), water, brine
  6. dry with materialdry with MgSO4
  7. concentrationconcentrate
  8. customPurify the residue on an ISCO RediSep 10-gram silicagel cartridge
  9. washeluting with ethyl acetate
  10. additionCombine product containing fractions
  11. concentrationconcentrate

Sources & evidence

ORD record
ord-40c2225696bc4be7b395db7420a28b7b
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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