1-Chloroethyl chloroformate → 8-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid

HRID 43156Notes

Reaction equation

HRID 43156 reaction equation
ClC(OC(Cl)C)=[O:3].COC1C=CC(CN2CCN(CC3C=CC(N[C:29]([C:31]4[C:32]5[N:33]=[CH:34][CH:35]=[N:36][C:37]=5[C:38]([C:41]5[CH:46]=[C:45]([O:47][CH3:48])[CH:44]=[C:43]([O:49][CH3:50])[CH:42]=5)=[CH:39][CH:40]=4)=[O:30])=NC=3)CC2)=CC=1>C1COCC1>[CH3:48][O:47][C:45]1[CH:46]=[C:41]([C:38]2[C:37]3[N:36]=[CH:35][CH:34]=[N:33][C:32]=3[C:31]([C:29]([OH:30])=[O:3])=[CH:40][CH:39]=2)[CH:42]=[C:43]([O:49][CH3:50])[CH:44]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 445131998-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acid {5-[4-(4-methoxybenzyl)-piperazin-1-ylmethyl]-pyridin-2-yl}-amide

Product 1

HCID 592928448-(3,5-Dimethoxy-phenyl)-quinoxaline-5-carboxylic acidYield 53.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

α-Chloroethyl chloroformate (19 μL, 0.17 mmol) was added to a cold (−78° C.) solution of 8-(3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid {5-[4-(4-methoxy-benzyl)-piperazin-1-ylmethyl]pyridin-2-yl}-amide (Example 116) (103 mg, 0.17 mmol) in THF (2 mL). The reaction mixture was stirred for 1 h at −78° C., quenched by addition of MeOH and concentrated. The residue was dissolved in MeOH (5 mL), heated to reflux for 3 h, allowed to cool. The resulting solid was collected by filtration, diluted in in DCM and a saturated aqueous solution of NaHCO3, and extracted with DCM. The organic phase was dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 91.5:7.5:1) followed by trituration in Et2O to afford 28 mg of the title compound as a white solid. Title compound: ESI-MS: 485.2 [M+H]+; tR=3.80 min (System 1); TLC: Rf=0.10 (DCM/MeOH/NH3aq, 91.5:7.5:1).

Workup

  1. customquenched by addition of MeOH
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in MeOH (5 mL)
  4. temperatureheated
  5. temperatureto reflux for 3 h
  6. temperatureto cool
  7. filtrationThe resulting solid was collected by filtration
  8. additiondiluted in in DCM
  9. extractiona saturated aqueous solution of NaHCO3, and extracted with DCM
  10. dry with materialThe organic phase was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel column chromatography (DCM/MeOH/NH3aq, 91.5:7.5:1)

Sources & evidence

ORD record
ord-8d8046c7e3954c319573c523e794f7b2
Source dataset
uspto-grants-2013_09
Patent number
US08536175B2

Reaction notes

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