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

HRID 1189839ノート

反応式

HRID 1189839 の反応式
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]

参加物

6

反応物 4

HCID 962WaterHCID 16682925TrimethylaluminumHCID 454899105-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinamineHCID 669146908-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid ethyl ester

生成物 1

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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-695000ccc5e84ffd852ab999adb57d63
出典データセット
uspto-grants-2014_03
特許番号
US08674099B2

反応ノート

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