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

HRID 43154Notes

Reaction equation

HRID 43154 reaction equation
C[Al](C)C.C([O:7][C:8]([C:10]1[C:11]2[N:12]=[CH:13][CH:14]=[N:15][C:16]=2[C:17]([C:20]2[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[C:22]([O:28][CH3:29])[CH:21]=2)=[CH:18][CH:19]=1)=O)C.[CH2:30]([N:32]1[CH2:37][CH2:36][N:35]([CH2:38][C:39]2[CH:40]=[CH:41][C:42]([NH2:45])=[N:43][CH:44]=2)[CH2:34][CH2:33]1)[CH3:31].O>C1(C)C=CC=CC=1>[CH2:30]([N:32]1[CH2:33][CH2:34][N:35]([CH2:38][C:39]2[CH:40]=[CH:41][C:42]([NH:45][C:8]([C:10]3[C:11]4[N:12]=[CH:13][CH:14]=[N:15][C:16]=4[C:17]([C:20]4[CH:21]=[C:22]([O:28][CH3:29])[CH:23]=[C:24]([O:26][CH3:27])[CH:25]=4)=[CH:18][CH:19]=3)=[O:7])=[N:43][CH:44]=2)[CH2:36][CH2:37]1)[CH3:31]

Participants

6

Reactant 4

HCID 962WaterHCID 16682925TrimethylaluminumHCID 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

Trimethyl aluminum (2 M in toluene, 0.37 mL, 0.74 mmol, 2.5 equiv) was added to a mixture of 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-33d127c707d948e392fb565b48665bab
Source dataset
uspto-grants-2013_09
Patent number
US08536175B2

Reaction notes

Loading…