1-Hydroxybenzotriazole → Ethyl 3-chloro-4-(1-methyl-3-indolylcarbonylamino)phenylacetate

HRID 1372781Notes

Reaction equation

HRID 1372781 reaction equation
CCN=C=NCCCN(C)C.Cl.[CH3:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([C:23]([OH:25])=O)=[CH:15]1.[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:29][C:28]=1[Cl:39].C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[Cl:39][C:28]1[CH:29]=[C:30]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:31]=[CH:32][C:27]=1[NH:26][C:23]([C:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:14]([CH3:13])[CH:15]=1)=[O:25]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 8540401-Methylindole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17859298(4-Amino-3-chloro-phenyl)-acetic acid ethyl ester

Product 1

HCID 17859282Ethyl 3-chloro-4-(1-methyl-3-indolylcarbonylamino)phenylacetateYield 30.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

In DMF (20 ml), EDC HCl (1.44 g, 7.49 mmol) was added to 1-methyl-3-indolylcarboxylic acid (1.01 g, 5.71 mmol), ethyl 4-amino-3-chlorophenylacetate (1.22 g, 5.71 mmol), HOBt (0.86 g, 6.34 mmol), and DMAP (0.14 g, 1.15 mmol) and the resulting mixture was stirred at 70° C. for 18 hours. After cooling to room temperature, the reaction mixture was added with water, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:1, v/v) eluate fractions, ethyl (3-chloro-4-((1-methyl-3-indolylcarbonyl)amino)phenyl)acetate (639 mg, 30%) was obtained as a yellow solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationdistilled under reduced pressure
  6. customto remove the solvent
  7. customThe residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:1

Sources & evidence

ORD record
ord-dc755bad3c594223a9a8408efd9fa4e5
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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