Hydrochloric Acid → 8-(4-aminomethylphenyl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid

HRID 1354191Notes

Reaction equation

HRID 1354191 reaction equation
Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18]CC)=[O:17])[C:6]2=[O:21].C(=O)([O-])[O-].[Na+].[Na+].Cl.[NH2:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.Cl>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.C(O)C>[NH2:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:14][CH2:15]2)[CH:8]=[C:7]([C:16]([OH:18])=[O:17])[C:6]3=[O:21])=[CH:33][CH:32]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27343114-Aminomethylphenylboronic acid hydrochlorideHCID 12071709ethyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

Product 1

HCID 230196868-(4-aminomethylphenyl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acidYield 60.4%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

350 mg of ethyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate was dissolved in 3.5 ml of toluene. 1.8 ml of ethanol, 1.8 ml of 2 M aqueous sodium carbonate solution, 235 mg of 4-aminomethylphenylboronic acid hydrochloride and 40 mg of bis(triphenylphosphine)palladium (II) chloride were added to the obtained solution, and they were heated under reflux in argon atmosphere for 6 hours. The reaction mixture was acidified with 1 N hydrochloric acid. After washing the aqueous layer with ethyl acetate, it was taken and then concentrated under reduced pressure. 2 ml of methanol and 1 ml of 1 N sodium hydroxide were added to the obtained residue, and they were stirred at 50° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in 10 ml of water and then neutralized with 1 N hydrochloric acid. The crystals thus formed were taken by the filtration to obtain 241 mg of 8-(4-aminomethylphenyl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid.

Workup

  1. temperaturewere heated
  2. temperatureunder reflux in argon atmosphere for 6 hours
  3. washAfter washing the aqueous layer with ethyl acetate, it
  4. concentrationconcentrated under reduced pressure
  5. addition2 ml of methanol and 1 ml of 1 N sodium hydroxide were added to the obtained residue, and they
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. dissolutionthe residue was dissolved in 10 ml of water
  8. customThe crystals thus formed
  9. filtrationwere taken by the filtration

Sources & evidence

ORD record
ord-34e98a201f374b0d82f40875b37b9877
Source dataset
uspto-grants-2007_05
Patent number
US07223773B2

Reaction notes

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