2-Mercaptobenzoic Acid → 4-Isopropyl-N-(6-piperazin-1-ylpyridin-3-yl)benzenesulfonamide

HRID 2251802Notes

Reaction equation

HRID 2251802 reaction equation
C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[N:45]=[CH:44][C:43]([NH:46][S:47]([C:50]3[CH:55]=[CH:54][C:53]([CH:56]([CH3:58])[CH3:57])=[CH:52][CH:51]=3)(=[O:49])=[O:48])=[CH:42][CH:41]=2)[CH2:36][CH2:35]1)C=C.SC1C=CC=CC=1C(O)=O>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:56]([C:53]1[CH:54]=[CH:55][C:50]([S:47]([NH:46][C:43]2[CH:44]=[N:45][C:40]([N:37]3[CH2:36][CH2:35][NH:34][CH2:39][CH2:38]3)=[CH:41][CH:42]=2)(=[O:48])=[O:49])=[CH:51][CH:52]=1)([CH3:58])[CH3:57]

Participants

6

Reactant 3

HCID 54432-Mercaptobenzoic Acid2×HCID 821241,4-Bis(diphenylphosphino)butaneHCID 9843972N-[6-(4-allylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide

Product 1

HCID 115956504-Isopropyl-N-(6-piperazin-1-ylpyridin-3-yl)benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent4×

Procedure

95 mg (0.1 mmol) of tris-(dibenzylideneacetone)dipalladium(0) and 44 mg (0.1 mmol) of 1,4-bis-(diphenylphosphino)butane were dissolved in 10 ml of tetrahydrofuran under an argon atmosphere. A solution composed of 1.1 g (2.75 mmol) of N-[6-(4-allylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide from Example 1.3I in 3 ml of tetrahydrofuran was then added dropwise to the reaction mixture. After that, a solution of 386 mg (2.5 mmol) of 2-mercaptobenzoic acid in 2 ml of tetrahydrofuran was added dropwise to the reaction mixture and the mixture was stirred at room temperature for 90 minutes. A solution of a further 386 mg (2.5 mmol) of 2-mercaptobenzoic acid in 2 ml of tetrahydrofuran was then added dropwise to the reaction mixture. The reaction mixture was stirred overnight at room temperature and, after that, the solvent was evaporated down to dryness. 150 ml of water were added to the resulting residue, after which the mixture was made acid with 1N aqueous hydrochloric acid and extracted three times with diethyl ether. The aqueous phase was then made alkaline, to pH>11, with a 1N aqueous solution of sodium hydroxide and subsequently extracted three times with dichloromethane. After that, the aqueous phase was adjusted to pH 8-9, saturated with an aqueous solution of sodium chloride and, after that, extracted several times with dichloromethane. 840 mg (82% of theory) of the title compound were obtained after the combined organic phases had been dried over sodium sulfate and the solvent had been filtered and evaporated down to dryness.

Workup

  1. additionwas then added dropwise to the reaction mixture
  2. stirringThe reaction mixture was stirred overnight at room temperature
  3. customafter that, the solvent was evaporated down to dryness
  4. addition150 ml of water were added to the resulting residue
  5. extractionextracted three times with diethyl ether
  6. extractionto pH>11, with a 1N aqueous solution of sodium hydroxide and subsequently extracted three times with dichloromethane
  7. extractionafter that, extracted several times with dichloromethane

Sources & evidence

ORD record
ord-8b4e8031d43d4be9b3c3a40baad2acf7
Source dataset
uspto-grants-2008_01
Patent number
US07320979B2

Reaction notes

Loading…