4-Methylmorpholine → 4-Bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-2-fluorobenzenesulfonamide

HRID 130438Notes

Reaction equation

HRID 130438 reaction equation
[CH3:1][C@H:2]1[NH:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[CH:10]=[CH:11][C:12]([O:16][CH3:17])=[C:13]([CH:15]=2)[NH2:14])[CH2:3]1.CN1CCOCC1.[Br:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[C:28]([F:36])[CH:27]=1>ClCCl>[Br:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([NH:14][C:13]2[CH:15]=[C:9]([N:4]3[CH2:3][C@H:2]([CH3:1])[NH:7][C@H:6]([CH3:8])[CH2:5]3)[CH:10]=[CH:11][C:12]=2[O:16][CH3:17])(=[O:33])=[O:34])=[C:28]([F:36])[CH:27]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 27363104-Bromo-2-fluorobenzene-1-sulfonyl chlorideHCID 590070635-(cis-3,5-Dimethyl-1-piperazinyl)-2-(methyloxy)aniline

Product 1

HCID 590070834-Bromo-N-[5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)phenyl]-2-fluorobenzenesulfonamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-(cis-3,5-dimethyl-1-piperazinyl)-2-(methyloxy)aniline (D4) (1.20 g, 5.09 mmol) in dichloromethane (35 ml) was treated with morpholinomethyl-polystyrene HL resin (2.43 g, 4.2 mmol/g loading, 10.2 mmol) followed by 4-bromo-2-fluorobenzenesulfonyl chloride (2.79 g, 10.2 mmol). The resulting solution was stirred at room temperature overnight, the resin was then filtered off, the solvent evaporated in vacuo and the residue was then passed through an SCX column eluting first with methanol and then by 2M ammonia in methanol. The basic fractions were combined and solvent evaporated in vacuo to afford a crude product which was dry loaded onto a column and purified further by chromatography using a Flashmaster and an elution gradient of 0 to 10% methanol in dichloromethane The relevant fractions were collected, combined and solvent evaporated to afford the title compound (E103). MS (ES+) m/e 472/474 [M+H]+.

Workup

  1. filtrationthe resin was then filtered off
  2. customthe solvent evaporated in vacuo
  3. washeluting first with methanol
  4. customsolvent evaporated in vacuo
  5. customto afford a crude product which
  6. customwas dry
  7. custompurified further by chromatography
  8. customan elution gradient of 0 to 10% methanol in dichloromethane The relevant fractions were collected
  9. customsolvent evaporated

Sources & evidence

ORD record
ord-041f5610500f43838fa3704de16aec37
Source dataset
uspto-grants-2008_06
Patent number
US07381728B2

Reaction notes

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