Trifluoroacetic acid → HCID 22710169, compound

HRID 352892Notes

Reaction equation

HRID 352892 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[NH:18][C:19]3[C:24]([CH:25]=2)=[CH:23][C:22]([Cl:26])=[CH:21][CH:20]=3)(=[O:16])=[O:15])[CH2:10][CH:9]1[CH2:27][C:28](O)=[O:29])=O)(C)(C)C.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:43]1([S:49]([NH2:52])(=[O:51])=[O:50])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C1CCN2C(=NCCC2)CC1.[F:64][C:65]([F:70])([F:69])[C:66]([OH:68])=[O:67]>O1CCCC1.ClCCl>[F:64][C:65]([F:70])([F:69])[C:66]([OH:68])=[O:67].[Cl:26][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([S:14]([N:11]1[CH2:12][CH2:13][NH:8][CH:9]([CH2:27][C:28](=[O:29])[NH:52][S:49]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)(=[O:51])=[O:50])[CH2:10]1)(=[O:15])=[O:16])=[CH:25]2

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7370BenzenesulfonamideHCID 682631,1'-Carbonyldiimidazole2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 22709504HCID 22709504, compound

Product 1

HCID 22710169HCID 22710169, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In tetrahydrofuran (10 ml) was dissolved 1-tert-butoxycarbonyl-2-carboxymethyl-4-[(5-chloroindol-2-yl)sulfonyl]piperazine (1.00 g), followed by the addition of carbonyldiimidazole (1.06 g). The resulting mixture was heated overnight under reflux. After cooling to room temperature, the reaction mixture was added with benzenesulfonamide (685 mg), 1,8-diazabicyclo[5.4.0]-7-undecene (0.64 ml) and carbonyldiimidazole (353 mg). The resulting mixture was heated under reflux for 1 hour. The reaction mixture was then concentrated under reduced pressure. Dichloromethane was added to the residue and the solid thus precipitated was filtered off. The filtrate was washed successively with 1N hydrochloric acid and saturated aqueous NaCl solution. The organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (Φ3.0×10.0 cm, dichloromethane:methanol=100:1), whereby pale brown foam was obtained. The resulting foam was dissolved in dichloromethane (10 ml), followed by the addition of trifluoroacetic acid (10 ml). After stirring at room temperature for 1 minute, the reaction mixture was concentrated under reduced pressure. Diethyl ether was added to the residue and the resulting precipitate was collected by filtration, whereby the title compound (496 mg, 31%) was obtained as colorless foam.

Workup

  1. temperatureThe resulting mixture was heated overnight
  2. temperatureunder reflux
  3. temperatureThe resulting mixture was heated
  4. temperatureunder reflux for 1 hour
  5. concentrationThe reaction mixture was then concentrated under reduced pressure
  6. additionDichloromethane was added to the residue
  7. customthe solid thus precipitated
  8. filtrationwas filtered off
  9. washThe filtrate was washed successively with 1N hydrochloric acid and saturated aqueous NaCl solution
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. distillationdistilled under reduced pressure
  12. customto remove the solvent
  13. customThe residue was purified by chromatography on a silica gel column (Φ3.0×10.0 cm, dichloromethane:methanol=100:1), whereby pale brown foam
  14. customwas obtained
  15. concentrationthe reaction mixture was concentrated under reduced pressure
  16. additionDiethyl ether was added to the residue
  17. filtrationthe resulting precipitate was collected by filtration, whereby the title compound (496 mg, 31%)
  18. customwas obtained as colorless foam

Sources & evidence

ORD record
ord-d9fa56f70bcb4c5897c2ca0b2b1c44bf
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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