Nitrogen mustard hydrochloride → 3-Bromo-8-(4-methyl-piperazin-1-yl)-quinoline

HRID 2116521Notes

Reaction equation

HRID 2116521 reaction equation
Cl.Cl[CH2:3][CH2:4][N:5]([CH2:7][CH2:8]Cl)[CH3:6].C(=O)([O-])[O-].[Na+].[Na+].[Br:16][C:17]1[CH:18]=[N:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][C:21]=2[NH2:27]>C(O)CCC.ClCCl>[Br:16][C:17]1[CH:18]=[N:19][C:20]2[C:25]([CH:26]=1)=[CH:24][CH:23]=[CH:22][C:21]=2[N:27]1[CH2:8][CH2:7][N:5]([CH3:6])[CH2:4][CH2:3]1

Participants

6

Reactant 3

HCID 5935Nitrogen mustard hydrochlorideHCID 10340Sodium CarbonateHCID 151125453-Bromoquinolin-8-amine

Product 1

HCID 673136243-Bromo-8-(4-methyl-piperazin-1-yl)-quinolineYield 49%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 6344DichloromethaneSolvent

Procedure

bis-(2-Chloroethyl)-methyl-amine hydrochloride (3.7 g, 19.2 mmol) and sodium carbonate (9.0 g, 85 mmol) were added to a suspension of 3-bromo-quinolin-8-ylamine (3.9 g, 17.5 mmol) (for synthesis see Gershon et al., Monatsh. Chem., 1991, 122, 935) in n-butanol (70 ml). The stirred suspension was heated at reflux for 72 h. The reaction mixture was cooled to ambient temperature, diluted with dichloromethane (300 ml) and the solution washed with water (300 ml), dried (MgSO4) and concentrated in vacuo to an oil. The oil was purified by chromatography over silica gel eluting with a gradient of methanol/dichloromethane to afford the title compound (D1) as an oil (2.6 g, 8.5 mmol, 49%);

Workup

  1. temperatureThe stirred suspension was heated
  2. temperatureat reflux for 72 h
  3. washthe solution washed with water (300 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo to an oil
  6. customThe oil was purified by chromatography over silica gel eluting with a gradient of methanol/dichloromethane

Sources & evidence

ORD record
ord-66913ffcfe854603979e57cc5405e3a8
Source dataset
uspto-grants-2008_10
Patent number
US07439244B2

Reaction notes

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