1-(2-Hydroxyethyl)piperazine → 4-Chloro-7-{6-[4-(2-hydroxyethyl)piperazin-1-ylcarbonyl]-1-methylindol-2-yl}isoindolinone

HRID 21105Notes

Reaction equation

HRID 21105 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([CH3:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][CH:16]=[C:15]([C:20]([OH:22])=O)[CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:24].CCN=C=NCCCN(C)C.C1C=C2N=NN(O)C2=CC=1.O.[OH:47][CH2:48][CH2:49][N:50]1[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1>CN(C=O)C.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([CH3:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][CH:16]=[C:15]([C:20]([N:53]2[CH2:54][CH2:55][N:50]([CH2:49][CH2:48][OH:47])[CH2:51][CH2:52]2)=[O:22])[CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:24]

Participants

8

Reactant 4

HCID 76771-(2-Hydroxyethyl)piperazineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68489371HCID 68489371, compound

Product 1

HCID 684887384-Chloro-7-{6-[4-(2-hydroxyethyl)piperazin-1-ylcarbonyl]-1-methylindol-2-yl}isoindolinoneYield 62.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a similar manner to Step 1 of Example 20, Compound 158 (20.0 mg, 0.0587 mmol) was dissolved in DMF (1 mL), and the solution was treated with EDCI (23 mg, 0.12 mmol), HOBT monohydrate (7.9 mg, 0.059 mmol) and 1-(2-hydroxyethyl)piperazine (31 mg, 0.24 mmol). The mixture was added with water and ethyl acetate, and then extracted with 1 mol/L hydrochloric acid. The aqueous layer was added with sodium carbonate to adjust the pH to 9 and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in chloroform, and the solution was added with hexane and stirred for 30 minutes. The solid was collected by filtration, washed with hexane and dried under reduced pressure to obtain Compound 160 (16.6 mg, yield 62%).

Workup

  1. extractionextracted with 1 mol/L hydrochloric acid
  2. additionThe aqueous layer was added with sodium carbonate
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. dissolutionThe residue was dissolved in chloroform
  8. additionthe solution was added with hexane
  9. filtrationThe solid was collected by filtration
  10. washwashed with hexane
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-92ce77d3879d4dc2aeeb554b9c53b30d
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Reaction notes

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