Tetrahydrofuran → 2-{4-[6-(3-Dipropylamino-propyl)-pyridin-2-yl]-benzyl}-isoindol-1,3-dione

HRID 2080805Notes

Reaction equation

HRID 2080805 reaction equation
[CH2:1]1[CH2:5]OC[CH2:2]1.Cl[C:7]1[N:12]=[C:11]([C:13]2[CH:30]=[CH:29][C:16]([CH2:17][N:18]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19]3=[O:28])=[CH:15][CH:14]=2)[CH:10]=[CH:9][CH:8]=1.[F-].[Cs+]>ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CN(C=O)C>[CH2:11]([N:12]([CH2:2][CH2:1][CH3:5])[CH2:7][CH2:8][CH2:9][C:7]1[N:12]=[C:11]([C:13]2[CH:30]=[CH:29][C:16]([CH2:17][N:18]3[C:19](=[O:28])[C:20]4[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:26]3=[O:27])=[CH:15][CH:14]=2)[CH:10]=[CH:9][CH:8]=1)[CH2:13][CH3:14]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 25953Cesium fluorideHCID 23155514HCID 23155514, compound

Product 1

HCID 231554522-{4-[6-(3-Dipropylamino-propyl)-pyridin-2-yl]-benzyl}-isoindol-1,3-dione

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

An anhydrous THF solution (1.0 ml) containing 2-propenyl dipropylamine (158 mg) was cooled with ice and a 0.5 mol/l 9-borabicyclo-[3,3,1]-nonane(9-BBN)/THF solution (2.06 ml) was dropped thereto. The whole was gradually warmed to room temperature and stirred for 5 hours. After that, a 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (PdCl2 (dppf)) (210 mg) and the compound (300 mg) obtained in Example 36-3 were added thereto together with DMF (3.0 ml), and a 3 mol/l aqueous solution (0.86 ml) of cesium fluoride was added thereto. The whole was stirred at 80° C. for 23 hours and then heated to 100° C. and stirred for 2 hours. After the resultant was cooled to room temperature, a solid component was separated by filtration and the solvent was distilled off. The concentrate was dissolved in chloroform, washed with saturated aqueous sodium hydrogen carbonate solution, extracted with chloroform, and dried with anhydrous magnesium sulfate, followed by distillating off the solvent. The resultant residue was purified through silica gel column chromatography (chloroform/methanol), thereby obtaining the subject compound (44.0 mg) as a pale-brown liquid.

Workup

  1. temperaturewas cooled with ice
  2. stirringThe whole was stirred at 80° C. for 23 hours
  3. temperatureheated to 100° C.
  4. stirringstirred for 2 hours
  5. temperatureAfter the resultant was cooled to room temperature
  6. customa solid component was separated by filtration
  7. distillationthe solvent was distilled off
  8. dissolutionThe concentrate was dissolved in chloroform
  9. washwashed with saturated aqueous sodium hydrogen carbonate solution
  10. extractionextracted with chloroform
  11. dry with materialdried with anhydrous magnesium sulfate
  12. customThe resultant residue was purified through silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-41077428d64a41368aa5b27054cbf431
Source dataset
uspto-grants-2011_04
Patent number
US07932281B2

Reaction notes

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