2-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-isopropylimidazo[4,5-f]isoindole-5,7(1H,6H)-dione → 2-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-isopropyl-6,7-dihydroimidazo[4,5-f]isoindol-5(1H)-one

HRID 69372Notes

Reaction equation

HRID 69372 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][CH:10]([NH:12][C:13]1[CH:18]=[CH:17][NH:16][C:15](=[O:19])[C:14]=1[C:20]1[NH:36][C:23]2=[CH:24][C:25]3[C:26](=[O:35])[N:27]([CH:32]([CH3:34])[CH3:33])[C:28](=O)[C:29]=3[CH:30]=[C:22]2[N:21]=1)[CH3:11]>C(O)(=O)C.[Zn]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][CH:10]([NH:12][C:13]1[CH:18]=[CH:17][NH:16][C:15](=[O:19])[C:14]=1[C:20]1[NH:21][C:22]2=[CH:30][C:29]3[CH2:28][N:27]([CH:32]([CH3:34])[CH3:33])[C:26](=[O:35])[C:25]=3[CH:24]=[C:23]2[N:36]=1)[CH3:11]

Participants

4

Reactant 1

HCID 1363406572-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-isopropylimidazo[4,5-f]isoindole-5,7(1H,6H)-dione

Product 1

HCID 1363406562-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-isopropyl-6,7-dihydroimidazo[4,5-f]isoindol-5(1H)-one

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

2-(4-((1-(2,5-Difluorophenyl)propan-2-yl)amino)-2-oxo-1,2-dihydropyridin-3-yl)-6-isopropylimidazo[4,5-f]isoindole-5,7(1H,6H)-dione (0.115 g) and zinc powder (0.290 g) were suspended in acetic acid (10 mL). The reaction mixture was stirred and heated to reflux overnight under argon. Then, the solvent was removed under reduced pressure. The residue solid was stirred in 100 mL of saturated K2CO3 solution. The white solid was filtered out, dried under vacuum and extracted with CH2Cl2/MeOH (7/3 v/v) three times (300 mL). The extracts were concentrated to dryness. The residue was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give an off-white solid product, 0.055 g. MS: 475.9 [M+1]. 1H NMR (CDCl3, 500 MHz): δ 12.79 (s, 1H), 12.73 (s, 1H), 11.57 (d, 1H), 11.40 (d, 1H), 11.38 (d, 1H), 11.07 (d, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.70 (s, 1H), 7.50 (s, 1H), 7.30 (t, 1H), 7.26 (t, 1H), 7.06-6.97 (m, 5H), 6.91-6.86 (m, 2H), 6.13 (d, 2H), 4.77-4.71 (m, 2H), 4.43 (d, 5H), 4.07-4.00 (m, 2H), 3.18-3.13 (m, 2H), 2.93-2.89 (q, 2H), 1.74 (s, 6H), 1.44 (d, 8H), 1.34-1.23 (m, 16H).

Workup

  1. temperatureheated
  2. temperatureto reflux overnight under argon
  3. customThen, the solvent was removed under reduced pressure
  4. stirringThe residue solid was stirred in 100 mL of saturated K2CO3 solution
  5. filtrationThe white solid was filtered out
  6. customdried under vacuum
  7. extractionextracted with CH2Cl2/MeOH (7/3 v/v) three times (300 mL)
  8. concentrationThe extracts were concentrated to dryness
  9. customThe residue was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v)
  10. customto give an off-white solid product, 0.055 g

Sources & evidence

ORD record
ord-edd07a754c7b4a44862c662b6143f20b
Source dataset
uspto-grants-2014_09
Patent number
US08822500B2

Reaction notes

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