Phthalaldehyde → 2-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-2,3-dihydro-1H-isoindol-1-one

HRID 42254

Reaction equation

HRID 42254 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:11]=[C:12]([NH2:19])[C:13]4[CH:14]=[N:15][NH:16][C:17]=4[CH:18]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:20]1([CH:28]=O)[C:21]([CH:26]=[O:27])=[CH:22][CH:23]=[CH:24][CH:25]=1>C(OCC)(=O)C.C(O)(=O)C>[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:18]=[C:17]4[C:13]([CH:14]=[N:15][NH:16]4)=[C:12]([N:19]4[CH2:28][C:20]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[C:26]4=[O:27])[CH:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 2

HCID 4807PhthalaldehydeHCID 582680196-(1H-indol-4-yl)-1H-indazol-4-amine

Product 1

HCID 445404012-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-2,3-dihydro-1H-isoindol-1-oneYield 13.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

A mixture of 6-(1H-indol-4-yl)-1H-indazol-4-amine (100 mg, 0.403 mmol) and 1,2-benzenedicarbaldehyde (54 mg, 0.403 mmol) in ethyl acetate (1 ml) and acetic acid (0.25 ml) was stirred under a nitrogen atmosphere at room temperature for 3 h then overnight at room temperature. The reaction mixture was diluted with ethyl acetate (20 ml) and washed with 5% sodium bicarbonate solution (10 ml). The phases were separated, and the aqueous phase was extracted with further ethyl acetate (20 ml). The combined organic extracts (which contained a small amount of insoluble solid) were dried over anhydrous sodium sulphate, filtered and evaporated to give a yellow foam. This was partially dissolved in ethyl acetate (20 ml) and pre-adsorbed on silica (1.5 g). This silica was then added to the top of a 20 g silica SPE cartridge. The cartridge was eluted on a Flashmaster (II) instrument using a gradient of 0-100% ethyl acetate in cyclohexane over 30 min. Appropriate fractions were combined and evaporated to give the title compound (20 mg) as a pale yellow solid.

Workup

  1. customovernight
  2. customat room temperature
  3. washwashed with 5% sodium bicarbonate solution (10 ml)
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with further ethyl acetate (20 ml)
  6. dry with materialwere dried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customto give a yellow foam
  10. additionThis silica was then added to the top of a 20 g silica SPE cartridge
  11. washThe cartridge was eluted on a Flashmaster (II) instrument
  12. customover 30 min
  13. customevaporated

Sources & evidence

ORD record
ord-96c609e542224d3793995d64947c00c0
Source dataset
uspto-grants-2013_09
Patent number
US08536169B2

Linked notes

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