Oxalyl chloride → 4-[2-(Benzofurazan-5-yl)ethyl]-1-(indole-5-carbonyl)piperazine

HRID 1195677Notes

Reaction equation

HRID 1195677 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([OH:12])=O)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C(Cl)(=O)C(Cl)=O.[N:19]1[O:23][N:22]=[C:21]2[CH:24]=[C:25]([CH2:28][CH2:29][N:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[CH:26]=[CH:27][C:20]=12.C(N(C(C)C)CC)(C)C>C1COCC1.CN(C=O)C.ClCCl>[N:19]1[O:23][N:22]=[C:21]2[CH:24]=[C:25]([CH2:28][CH2:29][N:30]3[CH2:31][CH2:32][N:33]([C:10]([C:6]4[CH:5]=[C:4]5[C:9](=[CH:8][CH:7]=4)[NH:1][CH:2]=[CH:3]5)=[O:12])[CH2:34][CH2:35]3)[CH:26]=[CH:27][C:20]=12

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 742801H-Indole-5-Carboxylic AcidHCID 81531DiisopropylethylamineHCID 151663825-(2-Piperazin-1-ylethyl)-2,1,3-benzoxadiazole

Product 1

HCID 151663954-[2-(Benzofurazan-5-yl)ethyl]-1-(indole-5-carbonyl)piperazine

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Indole-5-carboxylic acid (57 mg, 0.35 mmol) was dissolved in THF (2 ml) and DMF (1 drop), then oxalyl chloride (37 μl, 54 mg, 0.42 mmol) was added. The mixture was stirred at room temperature for 3 hours, the solvent was evaporated under reduced pressure and the residue was dissolved in DMF (2 ml) and added to a stirred solution of 1-[2-(benzofurazan-5-yl)ethyl]piperazine (81 mg, 0.35 mmol) and diisopropylethylamine (91 μl, 68 mg, 0.52 mmol) in dichloromethane (1 ml). The mixture was stirred at room temperature for 24 hours, then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /CH3OH/NH3 ; 96:4:0.4 and crystallized from ethyl acetate/CHCl3 /hexane to give the piperazine as yellow microcrystals (16 mg, 12%), mp 180°-183° C.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (2 ml)
  3. stirringThe mixture was stirred at room temperature for 24 hours
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with CH2Cl2 /CH3OH/NH3
  7. custom96:4:0.4 and crystallized from ethyl acetate/CHCl3 /hexane

Sources & evidence

ORD record
ord-c929f49f7a3c4bd08781344c509356af
Source dataset
uspto-grants-1992_05
Patent number
US05112824

Reaction notes

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