Acetic Acid → 4-Chloro-7-{1-(tert-butoxycarbonyl)-5-[4-(methylsulfonyl)piperazin-1-ylmethyl]indol-2-yl}isoindolinone

HRID 21032Notes

Reaction equation

HRID 21032 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH:20]=O)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29].Cl.[CH3:31][S:32]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)(=[O:34])=[O:33].C(N(CC)CC)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][N:38]2[CH2:39][CH2:40][N:35]([S:32]([CH3:31])(=[O:34])=[O:33])[CH2:36][CH2:37]2)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 162656121-Methanesulfonylpiperazine hydrochlorideHCID 866282274-Chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone

Product 1

HCID 684936994-Chloro-7-{1-(tert-butoxycarbonyl)-5-[4-(methylsulfonyl)piperazin-1-ylmethyl]indol-2-yl}isoindolinoneYield 121.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

In a similar manner to Step 2 of Example 6, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (40.7 mg, 0.0991 mmol) was dissolved in acetonitrile (2 mL), and the solution was treated with 1-(methylsulfonyl)piperazine hydrochloride (80.0 mg, 0.399 mmol), triethylamine (0.110 mL, 0.789 mmol), acetic acid (0.115 mL, 2.01 mmol) and sodium triacetoxyborohydride (77.7 mg, 0.367 mmol). The reaction mixture was added with water and sodium carbonate to adjust the pH to 9. The mixture was 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 to obtain 4-chloro-7-{1-(tert-butoxycarbonyl)-5-[4-(methylsulfonyl)piperazin-1-ylmethyl]indol-2-yl}isoindolinone (67.2 mg).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-a05b1039d04b40759945762d22fa6bb6
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Reaction notes

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