2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → N-{3-(cis-3,5-Dimethyl-1-piperazinyl)-4-[(trifluoromethyl)oxy]phenyl}-4-(2-thienyl)benzenesulfonamide

HRID 130463Notes

Reaction equation

HRID 130463 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:13][S:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]3[S:24][CH:25]=[CH:26][CH:27]=3)=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].[CH3:28][C@H:29]1[CH2:34][NH:33][CH2:32][C@@H:31]([CH3:35])[NH:30]1.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]>[CH3:28][C@H:29]1[NH:30][C@@H:31]([CH3:35])[CH2:32][N:33]([C:2]2[CH:3]=[C:4]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[S:24][CH:25]=[CH:26][CH:27]=4)=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH:5]=[CH:6][C:7]=2[O:8][C:9]([F:12])([F:11])[F:10])[CH2:34]1

Participants

7

Reactant 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 23676156Sodium t-butoxideHCID 69198455N-{3-Bromo-4-[(trifluoromethyl)oxy]phenyl}-4-(2-thienyl)benzenesulfonamide

Product 1

HCID 59007044N-{3-(cis-3,5-Dimethyl-1-piperazinyl)-4-[(trifluoromethyl)oxy]phenyl}-4-(2-thienyl)benzenesulfonamide

Reagents, catalysts & solvents 2

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

Procedure

The product of Step 2 (162 mg, 0.34 mmol), cis-2,6-dimethyl piperazine (78 mg, 0.68 mmol), sodium tert-butoxide (169 mg, 0.68 mmol), tris(dibenzylideneacetone)dipalladium(0) (16 mg, 0.017 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (20 mg, 0.051 mmol) in dioxane (4 ml) were heated in a microwave reactor at 125° C. for 30 minutes. The reaction mixture 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 HPLC to afford the title compound (E245). MS (ES+) m/e 512 [M+H]+.

Workup

  1. washThe reaction mixture was applied to an SCX ion exchange cartridge (Varian bond-elute)
  2. washwashed with methanol and 2M ammonia in methanol
  3. concentrationThe combined basic fractions were concentrated in vacuo
  4. customthe residue purified by mass

Sources & evidence

ORD record
ord-6c0eb222b8b44af7b6c2cde901ab3206
Source dataset
uspto-grants-2008_06
Patent number
US07381728B2

Reaction notes

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