2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → N-[2-(Methyloxy)-5-(cis-3,4,5-trimethyl-1-piperazinyl)phenyl]-4-(2-thienyl)benzenesulfonamide

HRID 130471

Reaction equation

HRID 130471 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:7]=1.[CH3:25][N:26]1[C@H:31]([CH3:32])[CH2:30][NH:29][CH2:28][C@@H:27]1[CH3:33].CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>O1CCOCC1.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]>[CH3:24][O:23][C:5]1[CH:4]=[CH:3][C:2]([N:29]2[CH2:30][C@H:31]([CH3:32])[N:26]([CH3:25])[C@H:27]([CH3:33])[CH2:28]2)=[CH:7][C:6]=1[NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)=[CH:14][CH:13]=1)(=[O:11])=[O:10]

Participants

7

Reactant 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 30720221(2R,6S)-1,2,6-TrimethylpiperazineHCID 69197888N-[5-Bromo-2-(methyloxy)phenyl]-4-(2-thienyl)benzenesulfonamide

Product 1

HCID 59007104N-[2-(Methyloxy)-5-(cis-3,4,5-trimethyl-1-piperazinyl)phenyl]-4-(2-thienyl)benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

The product of Step 2 (200 mg, 0.47 mmol), cis-1,2,6-trimethyl piperazine (118 mg, 0.94 mmol), sodium tert-butoxide (90 mg, 0.94 mmol), tris(dibenzylideneacetone)dipalladium(0) (22 mg, 0.024 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (28 mg, 0.071 mmol) in dioxane (10 ml) was heated at reflux for 16 hours. After cooling to room temperature the solution was concentrated in vacuo. The residue was applied to an SCX ion exchange cartridge (Varian bond-elute) and washed with methanol and 2M ammonia in methanol. The combined basic fractions were concentrated in vacuo and the residue purified by mass directed autoprep to afford the title product (E277). MS (ES+) 472 [M+H]+.

Workup

  1. temperatureat reflux for 16 hours
  2. concentrationwas concentrated in vacuo
  3. washThe residue was applied to an SCX ion exchange cartridge (Varian bond-elute)
  4. washwashed with methanol and 2M ammonia in methanol
  5. concentrationThe combined basic fractions were concentrated in vacuo
  6. customthe residue purified by mass

Sources & evidence

ORD record
ord-3ed538457f03455e999eb27dbda60181
Source dataset
uspto-grants-2008_06
Patent number
US07381728B2

Linked notes

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