Nitrogen mustard hydrochloride → 8-(4-Methyl-piperazin-1-yl)-3phenylsulfonylquinoline

HRID 883529

Reaction equation

HRID 883529 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13])=[CH:7]2.Cl.Cl[CH2:23][CH2:24][N:25]([CH2:27][CH2:28]Cl)[CH3:26].C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(O)CCC>[CH3:26][N:25]1[CH2:27][CH2:28][N:1]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][C:8]([S:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)(=[O:14])=[O:13])=[CH:7]3)[CH2:23][CH2:24]1

Participants

7

Reactant 5

HCID 5935Nitrogen mustard hydrochloride2×HCID 10340Sodium CarbonateHCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 534255023-(Phenylsulfonyl)-8-quinolinamine

Product 1

HCID 99291628-(4-Methyl-piperazin-1-yl)-3phenylsulfonylquinoline

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 8-amino-3-phenylsulfonylquinoline (D5) (38.8 g, 137 mmol) in n-butanol (360 ml) was treated with bis-(2-chloroethyl)-methyl-amine hydrochloride (40 g, 138 mmol) and sodium carbonate (72 g, 0.68 mol). The mixture was heated to a vigorous reflux (˜100° C.) for 16 h then a further portion of bis-(2-chloroethyl)-methyl-amine hydrochloride (25 g, 86 mmol) introduced and heating continued for a further 4 h. The solution was cooled and a 1:1 mixture of saturated aqueous sodium bicarbonate and aqueous 10% sodium thiosulphate solution (2 L) added. Stirring was continued at ambient temperature for 16 h then the aqueous phase was extracted with dichloromethane (3×500 ml), the combined organic phase dried over magnesium sulphate, evaporated in vacuo and subjected to chromatography on a Biotage Flash 75 apparatus (1 kg Silica gel) to afford the title compound (E1) as the free base form (11.6 g), identical spectroscopically to that prepared by the first method.

Workup

  1. temperatureThe mixture was heated to
  2. temperatureheating
  3. temperatureThe solution was cooled
  4. additionadded
  5. waitwas continued at ambient temperature for 16 h
  6. extractionthe aqueous phase was extracted with dichloromethane (3×500 ml)
  7. dry with materialthe combined organic phase dried over magnesium sulphate
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-e5e255e77d784840af65ccea5c23301c
Source dataset
uspto-grants-2012_08
Patent number
US08236947B2

Linked notes

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