Water → 8-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amide

HRID 2409717Notes

Reaction equation

HRID 2409717 reaction equation
C([O:3][C:4]([C:6]1[C:7]2[N:8]=[CH:9][CH:10]=[N:11][C:12]=2[C:13]([C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH3:25])[CH:17]=2)=[CH:14][CH:15]=1)=O)C.[CH2:26]([N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=2)[CH2:30][CH2:29]1)[CH3:27].O>C1(C)C=CC=CC=1>[CH2:26]([N:28]1[CH2:29][CH2:30][N:31]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([NH:41][C:4]([C:6]3[C:7]4[N:8]=[CH:9][CH:10]=[N:11][C:12]=4[C:13]([C:16]4[CH:17]=[C:18]([O:24][CH3:25])[CH:19]=[C:20]([O:22][CH3:23])[CH:21]=4)=[CH:14][CH:15]=3)=[O:3])=[N:39][CH:40]=2)[CH2:32][CH2:33]1)[CH3:27]

Participants

5

Reactant 3

HCID 962WaterHCID 454899105-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinamineHCID 669146908-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid ethyl ester

Product 1

HCID 592929588-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-amideYield 35.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

8-(3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid ethyl ester (Step 115.1) (100 mg, 0.30 mmol) and 5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-ylamine (Step 26.1; purified by column chromatography) (78 mg, 0.36 mmol, 1.2 equiv) in toluene (2 mL). The reaction mixture was stirred for 1 h at rt, heated to reflux, stirred for 3 h, allowed to cool, poured onto EtOAc and H2O, and filtered through a pad of celite. The filtrate was extracted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 94:5:1) followed by reverse-phase preparative HPLC to afford 54 mg of the title compound as a pale yellow solid. Title compound: ESI-MS: 513.2 [M+H]+; tR=3.54 min (System 1); TLC: Rf=0.29 (DCM/MeOH/NH3aq, 94:5:1).

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. stirringstirred for 3 h
  4. temperatureto cool
  5. filtrationfiltered through a pad of celite
  6. extractionThe filtrate was extracted with EtOAc
  7. washThe organic phase was washed with H2O and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 94:5:1)

Sources & evidence

ORD record
ord-566bcd833db34322b43688e3cf74ab03
Source dataset
uspto-grants-2014_08
Patent number
US08815901B2

Reaction notes

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