Triethylamine → 4-Methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide

HRID 978300Notes

Reaction equation

HRID 978300 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][CH2:9]2)=[C:4]([NH2:18])[CH:3]=1.C(N(CC)CC)C.C1(O[C:33](Cl)=[O:34])C=CC=CC=1.[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>ClCCl.O>[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([C:33]([NH:18][C:4]2[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][C:5]=2[N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][CH2:9]2)=[O:34])[CH2:39][CH2:38]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformate2×HCID 531671-MethylpiperazineHCID 138129315-Bromo-2-[3,4-dihydro-1(2H)-quinolinyl]aniline

Product 1

HCID 138129394-Methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamideYield 61.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

1-(4-Bromo-2-aminophenyl)-1,2,3,4-tetrahydroquinoline (10.6 g, 0.035 mole) was dissolved on a steam bath in dichloromethane (150 ml). The solution was cooled to -5° C. in ice/methanol and triethylamine (5.01 g, 0.050 mole) was added in one portion, followed by a solution of phenylchloroformate (7.85 g, 0.050 mole) dissolved in dichloromethane (10 ml), dropwise over 15 minutes. The mixture was stirred 1 hour in the cold, 2 hours at room temperature, and an additional charge of phenylchloroformate (1.57 g, 0.010 mole) was added. After one hour, a solution of N-methylpiperazine (14.1 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added over 0.5 hour. The reaction mixture was stirred under nitrogen at room temperature overnight. Water (100 ml) was added and the mixture was stirred 0.5 hour. The organic phase was separated, washed 4 times with water, dried over anhydrous sodium sulfate, and evaporated in a 100° C. bath in vacuo. The residue was dissolved in toluene (40 ml), adsorbed on a column of silica gel (500 g) packed in toluene and eluted with dichloromethane-methanol (98:2). The appropriate fractions were combined and evaporated to give 9.2 g (61%) of product, as an oil.

Workup

  1. additionwas added
  2. waitAfter one hour
  3. additionwas added over 0.5 hour
  4. stirringThe reaction mixture was stirred under nitrogen at room temperature overnight
  5. stirringthe mixture was stirred 0.5 hour
  6. customThe organic phase was separated
  7. washwashed 4 times with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. customevaporated in a 100° C. bath in vacuo
  10. dissolutionThe residue was dissolved in toluene (40 ml)
  11. washeluted with dichloromethane-methanol (98:2)
  12. customevaporated

Sources & evidence

ORD record
ord-13a98f5f3ce24e56a50885170e59c164
Source dataset
uspto-grants-1987_05
Patent number
US04663453

Reaction notes

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