1,1'-Carbonyldiimidazole → HCID 136007785, compound

HRID 410021Notes

Reaction equation

HRID 410021 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][C:15]([OH:21])=[CH:16][CH:17]=2)[O:12][C:11]=1[C:22]([F:25])([F:24])[F:23])[C:5]#[N:6].Cl.[OH:27]N.C1N=CN([C:34]([N:36]2C=NC=C2)=[O:35])C=1>CCO>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[NH:36][C:34](=[O:27])[O:35][N:6]=2)[CH:7]=[CH:8][C:9]=1[C:10]1[C:19](=[O:20])[C:18]2[C:13](=[CH:14][C:15]([OH:21])=[CH:16][CH:17]=2)[O:12][C:11]=1[C:22]([F:25])([F:23])[F:24]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 67365153HCID 67365153, compound

Product 1

HCID 136007785HCID 136007785, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

3-Chloro-4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)benzonitrile (0.3 g, 0.8 mmol) was dissolved in EtOH (5 ml) and cooled with an ice bath. Hydroxyamine HCl salt (46 mg, 0.85 eq.) and TEA (0.11 ml, 1 eq.) were added. The reaction mixture was stirred overnight at room temperature. The solvent was removed and the residue (0.4 g) was suspended in anhydrous THF (5 ml). After addition of CDI (0.24 g, 1.5 eq.) and TEA (0.13 ml), the suspended solution was stirred and heated at 50° C. overnight. After removal of THF, the mixture was suspended in water (15 ml) and the pH was adjusted to 8. The aqueous layer was extracted with EtOAc (10 ml×2). Then, the aqueous layer was acidified to pH˜2 and was extracted with EtOAc (15 ml×4). The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After removal of the solvent, the crude product was purified by prep-HPLC to afford desired product in Example 18 (44 mg, 10%) as tan solid.

Workup

  1. temperaturecooled with an ice bath
  2. customThe solvent was removed
  3. stirringthe suspended solution was stirred
  4. temperatureheated at 50° C. overnight
  5. customAfter removal of THF
  6. extractionThe aqueous layer was extracted with EtOAc (10 ml×2)
  7. extractionwas extracted with EtOAc (15 ml×4)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. customAfter removal of the solvent
  11. customthe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-2184f81ac70f42a4b4a5274890993f29
Source dataset
uspto-grants-2014_06
Patent number
US08759548B2

Reaction notes

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