Hydrochloric Acid → HCID 66926202, compound

HRID 41970Notes

Reaction equation

HRID 41970 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[CH:13][C:14]([N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20](C(O)=O)[CH2:19][CH2:18]3)=[N:15][CH:16]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].Cl.C([O-])(O)=O.[Na+]>O1CCOCC1.ClCCl>[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[CH:13][C:14]([N:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[NH:20][CH2:19][CH2:18]3)=[N:15][CH:16]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 67979887HCID 67979887, compound

Product 1

HCID 66926202HCID 66926202, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

41 g of tert-butyl ester of 4-[5-(4-tert-butyl-piperazin-1-yl)pyridin-2-yl]-3,4-dihydro-2H-quinoxaline-1-carboxylic acid is put in a 1-liter three-necked flask under nitrogen atmosphere. 132 ml of dichloromethane is added, the reaction mixture is cooled on an ice bath and 257 ml of 4M solution of hydrochloric acid in dioxane is added dropwise. The temperature is allowed to return slowly to room temperature and then it is stirred for 2 h. The reaction mixture is diluted with dichloromethane, then it is cooled on an ice bath and saturated solution of NaHCO3 is added to pH=8. It is left to settle and the aqueous phase is extracted with dichloromethane. The organic phases are washed with water, then the combined organic phases are dried over Na2SO4, filtered on a frit and concentrated. The raw product obtained is chromatographed on silica gel, eluting with a gradient in the range from 100% dichloromethane to a dichloromethane/ethyl acetate/methanol/concentrated aqueous ammonia mixture in the proportions 70/25/5/1 and then with a dichloromethane/methanol/concentrated aqueous ammonia mixture in the proportions 90/10/1. 0.3 g of 1-[5-(4-tert-butyl-piperazin-1-yl)pyridin-2-yl]-1,2,3,4-tetrahydroquinoxaline is obtained.

Workup

  1. temperaturethe reaction mixture is cooled on an ice bath
  2. customto return slowly to room temperature
  3. temperatureit is cooled on an ice bath
  4. waitIt is left
  5. extractionthe aqueous phase is extracted with dichloromethane
  6. washThe organic phases are washed with water
  7. dry with materialthe combined organic phases are dried over Na2SO4
  8. filtrationfiltered on a frit
  9. concentrationconcentrated
  10. customThe raw product obtained
  11. customis chromatographed on silica gel
  12. washeluting with a gradient in the range from 100% dichloromethane to a dichloromethane/ethyl acetate/methanol/concentrated aqueous ammonia mixture in the proportions 70/25/5/1

Sources & evidence

ORD record
ord-28f058dfc0a243e5af784e928c5bc6f2
Source dataset
uspto-grants-2013_09
Patent number
US08536173B2

Reaction notes

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