Triphenylphosphine → 4-(1-(2-(1,3-dioxoisoindolin-2-yl)-2-methylpropyl)-1H-pyrazol-3-yl)-2-methylbenzonitrile

HRID 872520Notes

Reaction equation

HRID 872520 reaction equation
O[CH2:2][C:3]([N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]1=[O:16])([CH3:5])[CH3:4].[CH3:17][C:18]1[CH:25]=[C:24]([C:26]2[CH:30]=[CH:29][NH:28][N:27]=2)[CH:23]=[CH:22][C:19]=1[C:20]#[N:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[O:16]=[C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:14](=[O:15])[N:6]1[C:3]([CH3:5])([CH3:4])[CH2:2][N:28]1[CH:29]=[CH:30][C:26]([C:24]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[C:18]([CH3:17])[CH:25]=2)=[N:27]1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 8277892-(1-hydroxy-2-methylpropan-2-yl)-2,3-dihydro-1H-isoindole-1,3-dioneHCID 5363146Diisopropyl azodicarboxylate2×HCID 178422844HCID 178422844, compound

Product 1

HCID 706566914-(1-(2-(1,3-dioxoisoindolin-2-yl)-2-methylpropyl)-1H-pyrazol-3-yl)-2-methylbenzonitrileYield 16.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(1-hydroxy-2-methylpropan-2-yl)isoindoline-1,3-dione (1.10 g; 5 mmol) and 2-methyl-4-(1H-pyrazol-3-yl)benzonitrile (0.366 g; 2.0 mmol) were dissolved in 5 ml of THF under nitrogen atmosphere. Triphenylphosphine (1.05 g; 4.0 mmol) and DIAD (0.79 ml; 4.0 mmol) were added and the reaction stirred at RT over the weekend. Additional triphenylphosphine (0.525 g; 2.0 mmol) and DIAD (0.39 ml; 2.0 mmol) were added and the mixture was stirred at RT for 2 days and then refluxed for 2 hours. Solvent was evaporated, 50 ml of water was added and the mixture was washed with 3×50 ml of DCM, dried over Na2SO4, filtered and evaporated to dryness. The crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane) to obtain 125 mg (16%) of the title product. 1H-NMR (400 MHz; CDCl3): δ 1.56 (s, 6H), 2.60 (s, 3H), 4.2-4.38 (m, 2H), 6.50 (d, 1H), 7.33-7.87 (m, 8H).

Workup

  1. stirringthe mixture was stirred at RT for 2 days
  2. temperaturerefluxed for 2 hours
  3. customSolvent was evaporated
  4. addition50 ml of water was added
  5. washthe mixture was washed with 3×50 ml of DCM
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe crude mixture was purified twice by CombiFlash (column: silica, eluent 0-100% EtOAc in heptane)

Sources & evidence

ORD record
ord-8e42fd57af2f41c99606ebf6247c4356
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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