5-Bromo-7-chloro-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-one → HCID 178515111, compound

HRID 2427769Notes

Reaction equation

HRID 2427769 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:5]2.C([Sn](CCCC)(CCCC)[C:26]1[N:27]=[CH:28][N:29](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:30]=1)CCC>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:11][C:9]1[CH:10]=[C:2]([C:26]2[N:27]=[CH:28][NH:29][CH:30]=2)[CH:3]=[C:4]2[C:8]=1[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:5]2

Participants

6

Reactant 2

HCID 116393035-Bromo-7-chloro-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-oneHCID 118281174-(Tributylstannyl)-1-tritylimidazole

Product 1

HCID 178515111HCID 178515111, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-Bromo-7-chloro-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-one (127 mg, 0.343 mmol), 4-Tributylstannanyl-1-trityl-1H-imidazole (300 mg, 0.514 mmol), and Pd(PPh3)4 (79 mg, 0.0514 mmol) in toluene (15 mL) stirred overnight at 110° C. The mixture was cooled, diluted with water and extracted with ethyl acetate. The organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue (7-Chloro-2-(4-chloro-benzyl)-5-(1-trityl-1H-imidazol-4-yl)-2,3-dihydro-isoindol-1-one) was dissolved in formic acid (5 mL) and stirred at room temperature for 18 hrs. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate. The organics were washed with 3N HCl (2×30 ml) and the aqueous washes were combined, neutralized with 1N NaOH, and extracted with ethyl acetate. The organics were washed with brine, and dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography (100% Ethyl acetate—5% 2M NH3 in MeOH/CH2Cl2) provided the title compound (22 mg, 18%). 1H NMR (300 MHz, CDCl3): δ 7.80 (s, 2H), 7.7.75 (s, 1H), 7.46 (s, 1H), 7.35-7.30 (m, 4H), 4.77 (s, 2H), 4.27 (s, 2H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with ethyl acetate
  3. washThe organics were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe resulting residue (7-Chloro-2-(4-chloro-benzyl)-5-(1-trityl-1H-imidazol-4-yl)-2,3-dihydro-isoindol-1-one) was dissolved in formic acid (5 mL)
  8. stirringstirred at room temperature for 18 hrs
  9. customThe solvent was removed in vacuo
  10. dissolutionthe residue was dissolved in ethyl acetate
  11. washThe organics were washed with 3N HCl (2×30 ml)
  12. extractionextracted with ethyl acetate
  13. washThe organics were washed with brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-b05bb04b710247e39cfbee2e46f4cb73
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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