1-Hydroxybenzotriazole → 4-{4-[(7-methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1645361Notes

Reaction equation

HRID 1645361 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]([OH:14])=O)=[C:8]2[CH3:15].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C=O>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:30]=[CH:31][C:32]([NH:35][C:12]([C:9]3[NH:10][C:11]4[C:7]([C:8]=3[CH3:15])=[CH:6][CH:5]=[CH:4][C:3]=4[O:2][CH3:1])=[O:14])=[CH:33][CH:34]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 6496147-Methoxy-3-methyl-1H-indole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11011301tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate

Product 1

HCID 593651564-{4-[(7-methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl esterYield 28.7%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A mixture of 7-methoxy-3-methyl-1H-indole-2-carboxylic acid (61 mg, 0.3 mmol), 4-(4-amino-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (83 mg, 0.3 mmol), N-hydroxybenzotriazole (61 mg, 0.45 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) in 1:1 dichloromethane/dimethylformamide was stirred at room temperature for overnight. After the reaction, solvent was concentrated. The resulted mixture was mixed with water and extracted with ethyl acetate twice. The organic layers were collected, combined, washed with brine before being dried over sodium sulfate, and then concentrated to give a solid. The crude product was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 0%-100% ethyl acetate in hexane) to give 40 mg of 4-{4-[(7-methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester as an off-white solid. LCMS calcd for C26H32N4O4 (m/e) 464, obsd 465 (M+H).

Workup

  1. customAfter the reaction, solvent
  2. concentrationwas concentrated
  3. additionThe resulted mixture was mixed with water
  4. extractionextracted with ethyl acetate twice
  5. customThe organic layers were collected
  6. washwashed with brine
  7. dry with materialbefore being dried over sodium sulfate
  8. concentrationconcentrated
  9. customto give a solid
  10. customThe crude product was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 0%-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-403afa8557694265a167efe2a2924eb6
Source dataset
uspto-grants-2012_02
Patent number
US08124766B2

Reaction notes

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