Potassium Carbonate → 6-Chloro-3,3-dimethyl-2-[3-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

HRID 1801193Notes

Reaction equation

HRID 1801193 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1)[C:11]([CH3:23])([CH3:22])[CH2:10]2)=[O:4].[CH3:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:29]3[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]3)[CH:16]=1)[C:11]([CH3:23])([CH3:22])[CH2:10]2)=[O:4]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 75605N,N-Dimethylglycine hydrochlorideHCID 674420582-(3-Bromo-phenyl)-6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

Product 1

HCID 674407496-Chloro-3,3-dimethyl-2-[3-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl esterYield 82.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture solution of 2-(3-bromo-phenyl)-6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (1.5 g, 3.7 mmol), 1-methyl-piperazine (2.5 g, 14.7 mmol), copper(I) iodide (282 mg, 1.48 mmol), N,N-dimethylglycine hydrochloride (413 mg, 2.96 mmol) and potassium carbonate (5.6 g, 40.7 mmol) in dimethyl sulfoxide (8.0 mL) was stirred at 120° C. for 16 hours. Then the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate (2×200 mL), washed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL), dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 6-chloro-3,3-dimethyl-2-[3-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (1.3 g, 80%) as a light yellow oil which was used for next step without further purification: LC/MS m/e calcd for C24H30ClN3O2 (M+H)+: 428.98, observed: 428.1.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (2×200 mL)
  2. washwashed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-78eaf98cda334dac9b0f1dfbff53196a
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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