1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-Butyl 2-(6-(3-chloro-1H-indole-2-carboxamido)-1H-indol-1-yl)acetate

HRID 453871Notes

Reaction equation

HRID 453871 reaction equation
CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:31][C:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[NH:34][C:33]=1[C:41]([OH:43])=O.[NH2:44][C:45]1[CH:53]=[C:52]2[C:48]([CH:49]=[CH:50][N:51]2[CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])=[CH:47][CH:46]=1>CN(C=O)C.ClCCl>[Cl:31][C:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[NH:34][C:33]=1[C:41]([NH:44][C:45]1[CH:53]=[C:52]2[C:48]([CH:49]=[CH:50][N:51]2[CH2:54][C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])=[CH:47][CH:46]=1)=[O:43]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 152903193-Chloro-1H-indole-2-carboxylic acidHCID 59473728tert-butyl 2-(6-amino-1H-indol-1-yl)acetate

Product 1

HCID 59473712tert-Butyl 2-(6-(3-chloro-1H-indole-2-carboxamido)-1H-indol-1-yl)acetateYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

DIPEA (2.5 equiv.), EDCI (2.73 mmol, 1.2 equiv.) and HOBt (2.73 mmol, 1.2 equiv.) were added at 0° C. to a solution of 3-chloro-1H-indole-2-carboxylic acid (2.27 mmol, 1.0 equiv.) in DMF (6 ml), and the mixture was stirred for 15 min. tert-Butyl 2-(6-amino-1H-indol-1-yl)acetate (intermediate A—for synthesis see above) (2.27 mmol, 1.0 equiv.) was dissolved in DMF (1 ml) and added, with stirring, and the reaction mixture was then stirred for 12 h at 25° C. The mixture was diluted with dichloromethane (50 ml), washed with sat. ammonium chloride solution (20 ml), water (20 ml) and sat. NaCl solution (20 ml), dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (10-15% ethyl acetate in hexane). Yield: 55%

Workup

  1. additionadded
  2. stirringthe reaction mixture was then stirred for 12 h at 25° C
  3. washwashed with sat. ammonium chloride solution (20 ml), water (20 ml) and sat. NaCl solution (20 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (10-15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d0a7d4753e7941c2939065ded2696b55
Source dataset
uspto-grants-2013_07
Patent number
US08492559B2

Reaction notes

Loading…