Phthalic Anhydride → 2-(1H-pyrrolo[2,3-b]pyridin-6-yl)-isoindole-1,3-dione

HRID 1396363Notes

Reaction equation

HRID 1396363 reaction equation
[NH:1]1[C:5]2=[N:6][C:7]([NH2:10])=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[C:11]1(=O)[O:16][C:14](=[O:15])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.C([O-])(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.C(OCC)(=O)C>[NH:1]1[C:5]2=[N:6][C:7]([N:10]3[C:14](=[O:15])[C:13]4[C:12](=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:11]3=[O:16])=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1

Participants

7

Reactant 4

HCID 6811Phthalic AnhydrideHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 104192271H-pyrrolo(2,3-b)pyridin-6-amine

Product 1

HCID 866897262-(1H-pyrrolo[2,3-b]pyridin-6-yl)-isoindole-1,3-dioneYield 75.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

1H-Pyrrolo[2,3-b]pyridin-6-ylamine (0.12 g, 0.9 mmol) was suspended in acetic acid (1.5 mL), then phthalic anhydride (133 mg, 0.9 mmol) and sodium acetate (118 mg, 1.44 mmol) were added and the mixture heated to 120° C. After 3 h, the mixture was concentrated in vacuo, the residue obtained dissolved in ethyl acetate, and then cooled to 0° C. Ice-water and sodium bicarbonate solution were added then the aqueous layer was extracted with ethyl acetate. The aqueous layer was adjusted to pH 6 with 1M HCl solution and was extracted twice more with ethyl acetate. The combined organic layers were dried over sodium sulfate then concentrated in vacuo. Purification by chromatography (silica, 20 to 70% ethyl acetate in hexanes) gave 2-(1H-pyrrolo[2,3-b]pyridin-6-yl)-isoindole-1,3-dione (179 mg, 75%) as a light brown solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.91 (br. s., 1H) 8.15 (d, J=7.9 Hz, 1H) 7.90-8.05 (m, 4H) 7.59-7.65 (m, 1H) 7.21 (d, J=7.9 Hz, 1H) 6.54-6.60 (m, 1H); LCMS (EI/CI) m/z: 264 [M+H].

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customthe residue obtained
  3. temperaturecooled to 0° C
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. extractionwas extracted twice more with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationthen concentrated in vacuo
  8. customPurification by chromatography (silica, 20 to 70% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-600d3eac2b0a40ca99396041e37af563
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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