Chlorosulfonic acid → HCID 90449895, compound

HRID 1411268Notes

Reaction equation

HRID 1411268 reaction equation
[C:1]([N:4]1[CH2:8][CH2:7][C:6]2([C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10](C(=O)C(F)(F)F)[CH2:9]2)[CH2:5]1)(=[O:3])[CH3:2].Cl[S:24]([OH:27])(=O)=[O:25].C(N(CC)C(C)C)(C)C.[CH3:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>C(Cl)Cl.O>[CH3:37][N:38]1[CH2:43][CH2:42][N:41]([S:24]([C:14]2[CH:15]=[C:16]3[C:6]4([CH2:7][CH2:8][N:4]([C:1](=[O:3])[CH3:2])[CH2:5]4)[CH2:9][NH:10][C:11]3=[CH:12][CH:13]=2)(=[O:27])=[O:25])[CH2:40][CH2:39]1

Participants

7

Reactant 4

HCID 24638Chlorosulfonic acidHCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 90449878HCID 90449878, compound

Product 1

HCID 90449895HCID 90449895, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-(1′-Acetylspiro[indoline-3,3′-pyrrolidin]-1-yl)-2,2,2-trifluoroethanone (1.19 g, 3.81 mmol) was dissolved in methylene chloride (10 mL). Thereafter, chlorosulfonic acid (1.27 mL, 19 mmol) was added to the above obtained solution under cooling on ice, and the thus obtained mixture was then stirred for 30 minutes. Thereafter, while stirring, the reaction solution was added dropwise to ice water, and was then extracted with chloroform. The obtained organic layer was washed with brine, and was then dried over anhydrous sodium sulfate, followed by concentration in vacuo. The obtained residue was dissolved in methylene chloride (20 mL). Thereafter, N,N-diisopropylethylamine (0.7 mL, 4 mmol) and 1-methylpiperazine (0.22 mL, 2 mmol) were added to the above obtained solution under cooling on ice, and the thus obtained mixture was then stirred at room temperature for 15 hours. Thereafter, the reaction solution was diluted with water, and was then extracted with chloroform. The obtained organic layer was washed with brine, and was then dried over anhydrous sodium sulfate, followed by concentration in vacuo. The obtained residue was dissolved in methanol (3 mL), and a saturated solution of ammonium-methanol (3 mL) was then added to the above obtained solution, followed by stirring the mixture at room temperature for 30 minutes. Thereafter, the reaction solution was concentrated in vacuo, and the obtained residue was then purified by silica gel column chromatography (chloroform:methanol=10:1) to obtain 1-(5-((4-methylpiperazin-1-yl)sulfonyl)spiro[indoline-3,3′-pyrrolidin]-1′-yl)ethanone (559 mg, 82%) in the form of a white solid.

Workup

  1. temperatureunder cooling on ice
  2. stirringThereafter, while stirring
  3. extractionwas then extracted with chloroform
  4. washThe obtained organic layer was washed with brine
  5. dry with materialwas then dried over anhydrous sodium sulfate
  6. concentrationfollowed by concentration in vacuo
  7. dissolutionThe obtained residue was dissolved in methylene chloride (20 mL)
  8. temperatureunder cooling on ice
  9. stirringthe thus obtained mixture was then stirred at room temperature for 15 hours
  10. extractionwas then extracted with chloroform
  11. washThe obtained organic layer was washed with brine
  12. dry with materialwas then dried over anhydrous sodium sulfate
  13. concentrationfollowed by concentration in vacuo
  14. dissolutionThe obtained residue was dissolved in methanol (3 mL)
  15. additiona saturated solution of ammonium-methanol (3 mL) was then added to the above obtained solution
  16. stirringby stirring the mixture at room temperature for 30 minutes
  17. concentrationThereafter, the reaction solution was concentrated in vacuo
  18. customthe obtained residue was then purified by silica gel column chromatography (chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-711381777e4e4fd2bd7c9ae8159a6138
Source dataset
uspto-grants-2014_12
Patent number
US08921576B2

Reaction notes

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