Dimethylformamide → 5-(2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid [2-(3,5-dimethylpiperazin-1-yl)ethyl)amide

HRID 1368508Notes

Reaction equation

HRID 1368508 reaction equation
[O:1]=[C:2]1[NH:3][C:4]2[C:9](/[C:10]/1=[CH:11]/[C:12]1[NH:16][C:15]([CH3:17])=[C:14]([C:18]([OH:20])=O)[C:13]=1[CH3:21])=[CH:8][CH:7]=[CH:6][CH:5]=2.[CH3:22][N:23]([CH:25]=O)[CH3:24].[CH3:27][N:28]([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[CH3:54][CH:55]1CN[CH2:58][CH:57](C)[N:56]1CCN>C(Cl)Cl.CO.C(N(CC)CC)C>[CH3:54][CH:55]1[NH:56][CH:57]([CH3:58])[CH2:24][N:23]([CH2:25][CH2:27][NH:28][C:18]([C:14]2[C:13]([CH3:21])=[C:12](/[CH:11]=[C:10]3\[C:2](=[O:1])[NH:3][C:4]4[C:9]\3=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:16][C:15]=2[CH3:17])=[O:20])[CH2:22]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 118328715-(2-Oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acidHCID 219156562-(2,6-Dimethylpiperazin-1-YL)ethanamine

Product 1

HCID 590694925-(2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid [2-(3,5-dimethylpiperazin-1-yl)ethyl)amideYield 50%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a stirred yellow muddy mixture of 5-[2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (112.8 mg, 0.4 mmol), DMF (0.5 mL) and triethylamine (0.111 mL) in a 20 mL reaction tube, was added BOP reagent (265 mg). The mixture became clear in 5 min. 2-(2,6-dimethylpiperazin-1-yl)ethylamine (68.6 mg) (see., Tapia, L. Alonso—Cires, P. Lopez-Tudanca, R. Mosquera, L. Labeaga, A. Innerarity, A. Orjales, J. Med. Chem., 1999, 42, 2870-2880) was added into the clear mixture. The resulting solution was stirred at room temperature over night. Thin layer chromatography (10% methanol in methylene chloride) showed that all the starting material had been converted into the product. The reaction mixture was evaporated to dryness and then purified by flash chromatography (CH2Cl2/CH3OH=20/1-15/1) followed by recrystalization to give 5-[2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid [2-(3,5-dimethylpiperazin-1-yl)ethyl)amide (83 mg, 50% yield).

Workup

  1. customin a 20 mL reaction tube
  2. addition, 1999, 42, 2870-2880) was added into the clear mixture
  3. customThe reaction mixture was evaporated to dryness
  4. custompurified by flash chromatography (CH2Cl2/CH3OH=20/1-15/1)
  5. customfollowed by recrystalization

Sources & evidence

ORD record
ord-0b272a53da814c35bd866d1fc3eb68c8
Source dataset
uspto-grants-2003_06
Patent number
US06573293B2

Reaction notes

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