2-Thiopheneboronic acid → N-[5-(cis-3,5-Dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-3-fluoro-4-(2-thienyl)benzenesulfonamide

HRID 130449Notes

Reaction equation

HRID 130449 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([N:18]3[CH2:23][C@H:22]([CH3:24])[NH:21][C@H:20]([CH3:25])[CH2:19]3)[CH:15]=[CH:14][C:13]=2[O:26][CH3:27])(=[O:10])=[O:9])=[CH:4][C:3]=1[F:28].[S:29]1[CH:33]=[CH:32][CH:31]=[C:30]1B(O)O.CC(C)([O-])C.[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][C@H:20]1[NH:21][C@@H:22]([CH3:24])[CH2:23][N:18]([C:16]2[CH:15]=[CH:14][C:13]([O:26][CH3:27])=[C:12]([NH:11][S:8]([C:5]3[CH:6]=[CH:7][C:2]([C:30]4[S:29][CH:33]=[CH:32][CH:31]=4)=[C:3]([F:28])[CH:4]=3)(=[O:10])=[O:9])[CH:17]=2)[CH2:19]1

Participants

7

Reactant 3

HCID 27339602-Thiopheneboronic acid2×HCID 23665647Potassium tert-butoxideHCID 590070604-Bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-3-fluorobenzenesulfonamide

Product 1

HCID 11533015N-[5-(cis-3,5-Dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-3-fluoro-4-(2-thienyl)benzenesulfonamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-3-fluorobenzenesulfonamide (E105) (100 mg, 0.21 mmol) and 2-thienylboronic acid (54 mg, 0.42 mmol) in DME (3 ml) was added potassium tert-butoxide (212 mg, 1.89 mmol) and tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.01 mmol) in water (1 ml) and the resulting mixture stirred in a microwave (set at high absorbance) at 100° C. for 30 minutes. Additional 2-thienylboronic acid (27 mg, 0.21 mmol) and tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.01 mmol) were then added and the mixture stirred in a microwave (set at high absorbance) at 100° C. for a further 45 minutes. The solvent was evaporated with addition of a few drops of toluene and the residue passed through an SCX column eluting with methanol followed by 2M ammonia in methanol. The abasic fractions were combined and the solvent evaporated. The crude product was purified by mass directed autoprep HPLC, the relevant fractions collected and solvent evaporated to afford the title compound (E114). MS (ES+) m/e 476 [M+H]+.

Workup

  1. stirringthe mixture stirred in a microwave (set at high absorbance) at 100° C. for a further 45 minutes
  2. customThe solvent was evaporated with addition of a few drops of toluene
  3. washeluting with methanol
  4. customthe solvent evaporated
  5. customThe crude product was purified by mass
  6. customthe relevant fractions collected
  7. customsolvent evaporated

Sources & evidence

ORD record
ord-578a764c98ce48abb55509723bb9dcd0
Source dataset
uspto-grants-2008_06
Patent number
US07381728B2

Reaction notes

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