Nitrogen → 2-cyclohexyl-8-[(E)-2-(1H-indol-5-yl)-ethenesulfonyl]-1,3,8-triaza-spiro[4.5]dec-1-en-4-one

HRID 1754928Notes

Reaction equation

HRID 1754928 reaction equation
[CH:1]1([C:7]2[NH:11][C:10](=[O:12])[C:9]3([CH2:17][CH2:16][N:15]([S:18]([CH:21]=[CH2:22])(=[O:20])=[O:19])[CH2:14][CH2:13]3)[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[CH:27]2.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.N#N>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(N(C)C)=O>[CH:1]1([C:7]2[NH:11][C:10](=[O:12])[C:9]3([CH2:17][CH2:16][N:15]([S:18](/[CH:21]=[CH:22]/[C:24]4[CH:25]=[C:26]5[C:30](=[CH:31][CH:32]=4)[NH:29][CH:28]=[CH:27]5)(=[O:20])=[O:19])[CH2:14][CH2:13]3)[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 5

HCID 947NitrogenHCID 8471TriethylamineHCID 249055-BromoindoleHCID 80271Tri-o-tolylphosphineHCID 668163772-Cyclohexyl-8-ethenesulfonyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one

Product 1

HCID 668166742-cyclohexyl-8-[(E)-2-(1H-indol-5-yl)-ethenesulfonyl]-1,3,8-triaza-spiro[4.5]dec-1-en-4-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Procedure

2-Cyclohexyl-8-ethenesulfonyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (60.0 mg, 0.184 mmol), 5-bromo-indole (72.0 mg, 0.367 mmol), palladium(II) acetate (4.1 mg, 0.0183 mmol), tris(o-tolyl)phosphine (11.2 mg, 0.0368 mmol), triethylamine (0.077 ml, 0.552 mmol) and DMA (0.6 ml) were mixed in a sealed test tube in an N2 atmosphere. This mixture was irradiated with microwaves (190° C., 20 min). The reaction mixture was cooled, and then quenched with saturated brine and extracted with ethyl acetate three times. The organic layers were combined, sequentially washed with water and saturated brine and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (CH2Cl2-MeOH) to give 2-cyclohexyl-8-[(E)-2-(1H-indol-5-yl)-ethenesulfonyl]-1,3,8-triaza-spiro[4.5]dec-1-en-4-one as a yellow form (40.6 mg, 50%).

Workup

  1. customThis mixture was irradiated with microwaves (190° C., 20 min)
  2. temperatureThe reaction mixture was cooled
  3. customquenched with saturated brine
  4. extractionextracted with ethyl acetate three times
  5. washsequentially washed with water and saturated brine
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (CH2Cl2-MeOH)

Sources & evidence

ORD record
ord-aba111a1b6c342e8b2ebbf36823b15ed
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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