(S)-2-(2-oxo-4-((1-(2,3,5,6-tetrafluorophenyl)propan-2-yl)amino)-1,2-dihydropyridin-3-yl)-6-(pyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione → HCID 136353611, compound

HRID 920473Notes

Reaction equation

HRID 920473 reaction equation
[O:1]=[C:2]1[C:7]([C:8]2[NH:27][C:11]3=[CH:12][C:13]4[C:14](=[O:26])[N:15]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[C:16](=[O:19])[C:17]=4[CH:18]=[C:10]3[N:9]=2)=[C:6]([NH:28][C@@H:29]([CH3:41])[CH2:30][C:31]2[C:36]([F:37])=[C:35]([F:38])[CH:34]=[C:33]([F:39])[C:32]=2[F:40])[CH:5]=[CH:4][NH:3]1>C(O)(=O)C.[Zn]>[OH:26][CH:14]1[C:13]2[CH:12]=[C:11]3[NH:27][C:8]([C:7]4[C:2](=[O:1])[NH:3][CH:4]=[CH:5][C:6]=4[NH:28][C@@H:29]([CH3:41])[CH2:30][C:31]4[C:32]([F:40])=[C:33]([F:39])[CH:34]=[C:35]([F:38])[C:36]=4[F:37])=[N:9][C:10]3=[CH:18][C:17]=2[C:16](=[O:19])[N:15]1[C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 1

HCID 136353563(S)-2-(2-oxo-4-((1-(2,3,5,6-tetrafluorophenyl)propan-2-yl)amino)-1,2-dihydropyridin-3-yl)-6-(pyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

Product 1

HCID 136353611HCID 136353611, compoundYield 32.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

Compound (S)-2-(2-oxo-4-((1-(2,3,5,6-tetrafluorophenyl)propan-2-yl)amino)-1,2-dihydropyridin-3-yl)-6-(pyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione (0.46 g, 0.82 mmol) and zinc powder (1.23 g, 18.8 mmol) were suspended in acetic acid (30 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 50 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 (150 mL). The extracts were concentrated to dryness. The residue was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give a white solid product, 0.15 g, 32.6% yield. MS: 563.0 [M−H]−. 1H NMR (DMSO-d6, 500 MHz): δ 13.21-13.19 (m, 1H), 11.30-11.29 (m, 1H), 11.13-11.09 (m, 1H), 9.08 (s, 1H), 8.41 (d, 1H, J=3.5 Hz), 8.26 (d, 1H, J=7.0 Hz), 8.11 (s, 0.5H), 7.98 (s, 0.5H), 7.90 (s, 0.5 Hz), 7.78-7.73 (m, 1.5H), 7.52-7.50 (m, 1H), 7.41-7.38 (m, 1H), 6.93-6.90 (m, 1H), 6.67-6.64 (m, 1H), 6.20-6.17 (m, 1H), 4.26-4.25 (m, 1H), 3.19-3.14 (m, 2H), 1.41 (d, 3H, J=5.0 Hz).

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 50 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 (150 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 a white solid product, 0.15 g, 32.6% yield

Sources & evidence

ORD record
ord-e2e99040d1b74e58aa4e9087405392ee
Source dataset
uspto-grants-2016_03
Patent number
US09273055B2

Reaction notes

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