Nitrogen → N-{4-[(E)-2-(2-cyclohexyl-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl)-vinyl]-3,5-dimethyl-phenyl}-acetamide

HRID 1754934Notes

Reaction equation

HRID 1754934 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[C:29]([CH3:30])=[CH:28][C:27]([NH:31][C:32](=[O:34])[CH3:33])=[CH:26][C:25]=1[CH3:35].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.O.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[C:29]([CH3:30])=[CH:28][C:27]([NH:31][C:32](=[O:34])[CH3:33])=[CH:26][C:25]=4[CH3:35])(=[O:20])=[O:19])[CH2:14][CH2:13]3)[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

9

Reactant 5

HCID 947Nitrogen2×HCID 8471Triethylamine2×HCID 80271Tri-o-tolylphosphine2×HCID 4246250N-(4-bromo-3,5-dimethylphenyl)acetamideHCID 668163772-Cyclohexyl-8-ethenesulfonyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one

Product 1

HCID 66816542N-{4-[(E)-2-(2-cyclohexyl-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl)-vinyl]-3,5-dimethyl-phenyl}-acetamideYield 41.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-cyclohexyl-8-ethenesulfonyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one (100.0 mg, 0.307 mmol), N-(4-bromo-3,5-dimethyl-phenyl)-acetamide (112. mg, 0.461 mmol), palladium(II) acetate (10 mg, 0.0461 mmol), tris(o-tolyl)phosphine (28 mg, 0.0922 mmol), triethylamine (0.128 ml, 0.922 mmol) and DMA (1.5 ml) was added to a sealed test tube in an N2 atmosphere. This mixture was heated with stirring at 130° C. for 13.5 hours. Palladium(II) acetate (10 mg, 0.0461 mmol), tris(o-tolyl)phosphine (28 mg, 0.0922 mmol) and triethylamine (0.128 ml, 0.922 mmol) were further added to the reaction mixture at room temperature in an N2 atmosphere, and the mixture was heated with stirring at 130° C. for 14 hours. The reaction mixture was cooled and water was then added. The aqueous layer was extracted with ethyl acetate (×3). The organic layers were combined and sequentially washed with water (×2) and saturated brine, and then dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (CH2Cl2-MeOH) to give N-{4-[(E)-2-(2-cyclohexyl-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-sulfonyl)-vinyl]-3,5-dimethyl-phenyl}-acetamide (61.4 mg, 41%).

Workup

  1. temperatureThis mixture was heated
  2. temperaturethe mixture was heated
  3. stirringwith stirring at 130° C. for 14 hours
  4. temperatureThe reaction mixture was cooled
  5. extractionThe aqueous layer was extracted with ethyl acetate (×3)
  6. washsequentially washed with water (×2) and saturated brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (CH2Cl2-MeOH)

Sources & evidence

ORD record
ord-dd294027572342558d54e6deff8e7932
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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