Water → 8-(2,6-Dichloro-3,5-dimethoxyphenyl)-3-[(4-ethyl-1-piperazinyl)methyl]-5-quinoxalinecarboxylic acid

HRID 2391818Notes

Reaction equation

HRID 2391818 reaction equation
[OH-:1].[K+].[Cl:3][C:4]1[C:9]([O:10][CH3:11])=[CH:8][C:7]([O:12][CH3:13])=[C:6]([Cl:14])[C:5]=1[C:15]1[C:24]2[N:23]=[CH:22][C:21]([CH2:25][N:26]3[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[CH2:28][CH2:27]3)=[N:20][C:19]=2[C:18]([C:34]#N)=[CH:17][CH:16]=1.ClC1C(OC)=CC(OC)=C(Cl)C=1C1C2N=C(CN3CCN(CC)CC3)C=NC=2C(C#N)=CC=1.[OH2:69]>C(O)CO>[Cl:14][C:6]1[C:7]([O:12][CH3:13])=[CH:8][C:9]([O:10][CH3:11])=[C:4]([Cl:3])[C:5]=1[C:15]1[C:24]2[N:23]=[CH:22][C:21]([CH2:25][N:26]3[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[CH2:28][CH2:27]3)=[N:20][C:19]=2[C:18]([C:34]([OH:69])=[O:1])=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 59292888HCID 59292888, compoundHCID 59292890HCID 59292890, compound

Product 1

HCID 592929568-(2,6-Dichloro-3,5-dimethoxyphenyl)-3-[(4-ethyl-1-piperazinyl)methyl]-5-quinoxalinecarboxylic acid

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Conditions

Temperature
150 °C

Procedure

A solution of KOH (0.818 g, 14.6 mmol, 10 equiv) in H2O (20 mL) was added to 710 mg (1.46 equiv) of a mixture of 8-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(4-ethyl-piperazin-1-ylmethyl)-quinoxaline-5-carbonitrile and 8-(2,6-dichloro-3,5-dimethoxy-phenyl)-2-(4-ethyl-piperazin-1-ylmethyl)-quinoxaline-5-carbonitrile (Step 82.2) (710 mg, 1.46 mmol) in ethylene glycol (20 mL). The reaction mixture was stirred at 150° C. for 3 h, allowed to cool to rt and washed with EtOAc (2×100 mL). The aqueous layer was acidified to pH 3-4 by addition of 1N HCl. The resulting suspension was filtered. The filtrate contains 8-(2,6-dichloro-3,5-dimethoxy-phenyl)-2-(4-ethyl-piperazin-1-ylmethyl)-quinoxaline-5-carboxylic acid (Step 83.1). The residue in the filter was triturated in 1N HCl (3 mL) and filtered. The filtrate was basified to pH 5 and extracted with DCM (2×100 mL). The organic layer was dried (Na2SO4), filtered and concentrated to afford 190 mg of the title compound as a white solid: ES-MS: 505.0/506.6 [M+H]+; tR=3.46 min (System 1).

Workup

  1. temperatureto cool to rt
  2. washwashed with EtOAc (2×100 mL)
  3. additionThe aqueous layer was acidified to pH 3-4 by addition of 1N HCl
  4. filtrationThe resulting suspension was filtered
  5. customThe residue in the filter was triturated in 1N HCl (3 mL)
  6. filtrationfiltered
  7. extractionextracted with DCM (2×100 mL)
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-361e283b2fe342a2955a31f01ca3ad0d
Source dataset
uspto-grants-2012_09
Patent number
US08273882B2

Reaction notes

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