Water → 2-{4-[2-(Benzhydryl-amino)-5-chloro-phenyl]-but-3-ynyl}-isoindole-1,3-dione

HRID 1392596Notes

Reaction equation

HRID 1392596 reaction equation
[CH:1]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1I)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH2:30]([N:34]1[C:42](=[O:43])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]1=[O:44])[CH2:31][C:32]#[CH:33].O>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[CH:1]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[C:33]#[C:32][CH2:31][CH2:30][N:34]1[C:42](=[O:43])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:35]1=[O:44])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 11171619N-(3-Butynyl)phthalimideHCID 11486936HCID 11486936, compound

Product 1

HCID 113863132-{4-[2-(Benzhydryl-amino)-5-chloro-phenyl]-but-3-ynyl}-isoindole-1,3-dioneYield 95%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×

Procedure

5 g(11.93 mmol, 1 eq) benzhydryl-(4-chloro-2-iodo-phenyl)-amine made in Example 1 was combined with 5 mL DMF. 0.42 g(0.598 mmol, 0.05 eq) dichlorobis-(triphenylphosphine)-palladium, 0.24 g(1.26 mmol, 0.11 eq) copper iodide and 1.8 g (17.58 mmol, 1.5 eq) triethylamine were added. The mixture was stirred at 25 C and 2.72 g (13.65 mmol, 1.14 eq) 2-but-3-ynyl-isoindole-1,3-dione was added in one portion. The mixture warmed to 40 C and was cooled back to room temperature. It became semi-solid after 2 h; an LC showed that at this time the reaction was complete. The mixture was diluted with 10 mL DMF and then 5 mL water was added slowly. Stirring was continued until solids precipitated. The vessel was cooled to 0-5 C and stirred at this temperature for 30 min. The resulting solid was collected by filtration and washed with 10 mL DMF/water 2:1 and 2×10 mL MeOH. The 8.78 g wet solid was dried at 40 C in vacuo for 14 h to obtain 5.55 g product (95%) with 95% purity.

Workup

  1. additionwas added in one portion
  2. temperatureThe mixture warmed to 40 C
  3. customafter 2 h
  4. customprecipitated
  5. temperatureThe vessel was cooled to 0-5 C
  6. stirringstirred at this temperature for 30 min
  7. filtrationThe resulting solid was collected by filtration
  8. washwashed with 10 mL DMF/water 2:1 and 2×10 mL MeOH
  9. dry with materialThe 8.78 g wet solid was dried at 40 C in vacuo for 14 h

Sources & evidence

ORD record
ord-b826e1db81d140a5a45b2cdde2114e3b
Source dataset
uspto-grants-2008_03
Patent number
US07342119B2

Reaction notes

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