Acetic Acid → HCID 136340666, compound

HRID 920512Notes

Reaction equation

HRID 920512 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([CH2:8][CH:9]([NH:11][C:12]2[CH:17]=[CH:16][NH:15][C:14](=[O:18])[C:13]=2[C:19]2[NH:37][C:22]3=[CH:23][C:24]4[C:25](=O)[N:26]([CH2:31][CH2:32][N:33]([CH3:35])[CH3:34])[C:27](=[O:30])[C:28]=4[CH:29]=[C:21]3[N:20]=2)[CH3:10])[CH:7]=1.[C:38](O)(=O)C>[Zn]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:38])=[C:6]([CH2:8][CH:9]([NH:11][C:12]2[CH:17]=[CH:16][NH:15][C:14](=[O:18])[C:13]=2[C:19]2[NH:37][C:22]3=[CH:23][C:24]4[CH2:25][N:26]([CH2:31][CH2:32][N:33]([CH3:35])[CH3:34])[C:27](=[O:30])[C:28]=4[CH:29]=[C:21]3[N:20]=2)[CH3:10])[CH:7]=1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 136340667HCID 136340667, compound

Product 1

HCID 136340666HCID 136340666, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst

Procedure

Compound 2-(4-(1-(5-fluorophenyl)propan-2-ylamino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-(dimethylamino)ethyl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione (1.32 g, 2.56 mmol) and zinc powder (4.01 g, 61.32 mmol) were suspended in acetic acid (60 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 a white solid product, 0.85 g, 74% yield. MS: 503.1 [M+H]+. 1H NMR (DMSO-d6, 300 MHz): δ 13.07 (s, 1H), 11.17 (s, 1H), 11.09-11.05 (m, 1H), 7.97 (s, 0.5H), 7.86 (s, 0.5H), 7.80 (s, 0.5H), 7.70 (s, 0.5H), 7.30-7.10 (m, 3H), 6.92-6.84 (m, 1H), 6.15-6.11 (m, 1H), 4.54 (s, 2H), 4.18-4.14 (m, 1H), 3.64 (t, 2H, J=6.0 Hz), 3.02-2.97 (m, 2H), 2.53-2.49 (m, 2H), 2.36 (d, 3H, J=3.9 Hz), 2.20 (s, 6H), 1.35-1.33 (m, 3H).

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 a white solid product, 0.85 g, 74% yield

Sources & evidence

ORD record
ord-bbbe01e85bb34c2388c835c5c543d751
Source dataset
uspto-grants-2016_03
Patent number
US09273055B2

Reaction notes

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