Iodoethanol → 8-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid {5-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-pyridin-2-yl}-amide

HRID 43134

Reaction equation

HRID 43134 reaction equation
I[CH2:2][CH2:3][OH:4].[N:5]1([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([NH:18][C:19]([C:21]3[C:22]4[N:23]=[CH:24][CH:25]=[N:26][C:27]=4[C:28]([C:31]4[C:36]([Cl:37])=[C:35]([O:38][CH3:39])[CH:34]=[C:33]([O:40][CH3:41])[C:32]=4[Cl:42])=[CH:29][CH:30]=3)=[O:20])=[N:16][CH:17]=2)[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1>CC#N>[OH:4][CH2:3][CH2:2][N:8]1[CH2:7][CH2:6][N:5]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([NH:18][C:19]([C:21]3[C:22]4[N:23]=[CH:24][CH:25]=[N:26][C:27]=4[C:28]([C:31]4[C:36]([Cl:37])=[C:35]([O:38][CH3:39])[CH:34]=[C:33]([O:40][CH3:41])[C:32]=4[Cl:42])=[CH:29][CH:30]=3)=[O:20])=[N:16][CH:17]=2)[CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 12225IodoethanolHCID 592928408-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (5-piperazin-1-ylmethyl-pyridin-2-yl)-amide

Product 1

HCID 592929508-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid {5-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-pyridin-2-yl}-amideYield 76.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Iodoethanol (26 μL, 0.33 mmol, 10 equiv) was added to a mixture of 8-(2,6-dichloro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid (5-piperazin-1-ylmethyl-pyridin-2-yl)-amide (Example 105) (18 mg, 0.033 mmol) in CH3CN (1 mL), under an argon atmosphere. The reaction mixture was stirred for 14 h at rt, quenched by addition of a saturated aqueous solution of NaHCO3 (50 mL) and extracted with EtOAc. The organic layer was washed with a saturated aqueous solution of NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography (DCM/NH3aq, 99:1→DCM/MeOH/NH3aq, 96:3:1) to afford 15 mg of the title compound as a yellow solid. Title compound: ESI-MS: 596.6/598.4 [M+H]+; tR=3.45 min (System 1); TLC: Rf=0.30 (DCM/MeOH, 9:1).

Workup

  1. customquenched by addition of a saturated aqueous solution of NaHCO3 (50 mL)
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with a saturated aqueous solution of NaHCO3
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (DCM/NH3aq, 99:1→DCM/MeOH/NH3aq, 96:3:1)

Sources & evidence

ORD record
ord-714e5fe39bf942dbbda0ae27238cdb2f
Source dataset
uspto-grants-2013_09
Patent number
US08536175B2

Linked notes

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