Hydrochloric Acid → 8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylic acid hydrochloride

HRID 1080190Notes

Reaction equation

HRID 1080190 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][N:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([C:18]([O:20]CC)=[O:19])[C:12]3=[O:23])[CH2:4][CH2:3]1.[OH-].[Na+].[ClH:26]>C1COCC1>[ClH:26].[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][N:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([C:18]([OH:20])=[O:19])[C:12]3=[O:23])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 15389003Ethyl 8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate

Product 1

HCID 882527158-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylic acid hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 0.865 g (2.75 mmol) of ethyl 8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate, from Step 1, in 12 mL of THF and 16.5 mL of a 0.5N aqueous solution of sodium hydroxide was heated, with stirring, at 75° C. for 8 hours. The THF was removed from the reaction mixture by distillation during the reaction. The concentrated reaction mixture was cooled to ambient temperature and adjusted to pH 2.0 with 10.5 mL of 1N aqueous hydrochloric acid solution. The aqueous solution was concentrated in vacuo to remove ~80% of the water and the concentrate was diluted with 50 mL of 95% ethyl alcohol. The solid was collected by filtration, washed with 2×5 mL of ethyl alcohol and dried in vacuo to afford the desired product. The product was recrystallized from ethyl alcohol/water (3:1 v/v) to afford 0.332 g (37% yield) of the title compound, m.p. 257°-258° C.; MS DCI-NH3 : 288 (M-Cl)+ 90%, 244 ((M-Cl)--CO2H)+ base, 270 (M-Cl--H2O)+ ; IR (KBr): 3420 (OH), 1645 (C=O) cm-1 ; 1H NMR (TFA) d 3.20 (m, 3H), 3.52 (dd, 2H, J=10 Hz), 4.02 (m, 4H), 4.63 (d, 2H, J=12 Hz), 7.41 (m, 2H), 7.65 (d, 1H, J=7.5 Hz), 8.26 (d, 1H, J=9 Hz), 9.18 (d, 1H, J=7.5 Hz). Analysis calculated for C15H18ClN3O3 +0.5H2O: C, 54.14; H, 5.75; N, 12.62. Found: C, 54.23; H, 5.54; N, 12.64.

Workup

  1. customThe THF was removed from the reaction mixture by distillation during the reaction
  2. customThe concentrated reaction mixture
  3. temperaturewas cooled to ambient temperature
  4. concentrationThe aqueous solution was concentrated in vacuo
  5. customto remove ~80% of the water
  6. additionthe concentrate was diluted with 50 mL of 95% ethyl alcohol
  7. filtrationThe solid was collected by filtration
  8. washwashed with 2×5 mL of ethyl alcohol
  9. customdried in vacuo

Sources & evidence

ORD record
ord-48eff59baafb439a9d908759a9fc61a1
Source dataset
uspto-grants-1996_12
Patent number
US05580872

Reaction notes

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