1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-Butyl 2-(5-(3-chloro-1H-pyrrole-2-carboxamido)-1H-indol-1-yl)acetate

HRID 453876Notes

Reaction equation

HRID 453876 reaction equation
CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[CH:21]1[CH:22]=[CH:23][C:24]2[N:29](O)N=N[C:25]=2[CH:26]=1.[Cl:31][C:32]1[CH:36]=[CH:35][NH:34][C:33]=1[C:37]([OH:39])=O.NC1C=C2C([CH:45]=[CH:46][N:47]2[CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=CC=1>C(Cl)Cl>[Cl:31][C:32]1[CH:36]=[CH:35][NH:34][C:33]=1[C:37]([NH:29][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][CH:23]=1)[N:47]([CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH:46]=[CH:45]2)=[O:39]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 221800183-chloro-1H-pyrrole-2-carboxylic acidHCID 59473728tert-butyl 2-(6-amino-1H-indol-1-yl)acetate

Product 1

HCID 86761958tert-Butyl 2-(5-(3-chloro-1H-pyrrole-2-carboxamido)-1H-indol-1-yl)acetateYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

DIPEA (4.0 equiv.), EDCI (1.5 equiv.) and HOBt (1.0 equiv.) were added at 0° C. to a solution of 3-chloro-1H-pyrrole-2-carboxylic acid (5.24 mmol, 1.0 equiv.) in DCM (25 ml). The mixture was stirred for 15 min at 25° C. and then cooled to 0° C. again. A solution of tert-butyl 2-(6-amino-1H-indol-1-yl)acetate (intermediate A—for synthesis see above) (5.24 mmol, 1.0 equiv.) in DCM (10 ml) was added, and the reaction mixture was stirred for 16 h at 25° C. It was then diluted with DCM (200 ml), washed with sat. ammonium chloride solution (2×50 ml), sat. sodium hydrogen carbonate solution (2×50 ml) and sat. NaCl solution (2×50 ml), dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography (6% methanol in DCM). Yield: 56%

Workup

  1. temperaturecooled to 0° C. again
  2. stirringthe reaction mixture was stirred for 16 h at 25° C
  3. washwashed with sat. ammonium chloride solution (2×50 ml), sat. sodium hydrogen carbonate solution (2×50 ml) and sat. NaCl solution (2×50 ml)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (6% methanol in DCM)

Sources & evidence

ORD record
ord-aa54ab38478940a6b956c07f1e2d7cd8
Source dataset
uspto-grants-2013_07
Patent number
US08492559B2

Reaction notes

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