Triethylamine → HCID 136047360, compound

HRID 410020Notes

Reaction equation

HRID 410020 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[C:7]([C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)=[C:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.Cl.N[OH:27].C(N(CC)CC)C.C1N=C[N:37]([C:40](N2C=NC=C2)=[S:41])C=1>C(O)C>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[C:7]([C:16]3[CH:23]=[CH:22][C:19]([C:20]4[NH:37][C:40](=[O:27])[S:41][N:21]=4)=[CH:18][CH:17]=3)=[C:8]([C:12]([F:15])([F:13])[F:14])[O:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 802641,1'-ThiocarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 67366080HCID 67366080, compound

Product 1

HCID 136047360HCID 136047360, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)benzonitrile (see Example 1, step 1 for synthesis) (250 mg, 0.76 mmol) and hydroxylamine hydrochloride (105 mg, 1.51 mmol) in absolute ethanol (2 ml) was added dropwise triethylamine (0.5 ml). The resulting mixture was heated to reflux for 2 hours. The volatiles were evaporated and the residue was dissolved in anhydrous THF (5 ml). TCDI (202 mg, 1.13 mmol) was added and the suspension was stirred at room temperature for 2 hours, partitioned between EtOAc (50 ml) and water (20 ml). The organic phase was separated, dried with anhydrous Na2SO4, filtered and concentrated. The residue was dissolved in THF (5 ml), BF3-Et2O was added and stirred at room temperature for 2 hours. Workup with 1N HCl, then the volatiles were evaporated and the residue was purified by prep-HPLC to afford the desired product in Example 11 (17.5 mg, 5%) as a white solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 2 hours
  3. customThe volatiles were evaporated
  4. dissolutionthe residue was dissolved in anhydrous THF (5 ml)
  5. custompartitioned between EtOAc (50 ml) and water (20 ml)
  6. customThe organic phase was separated
  7. dry with materialdried with anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in THF (5 ml)
  11. additionBF3-Et2O was added
  12. stirringstirred at room temperature for 2 hours
  13. customWorkup with 1N HCl, then the volatiles were evaporated
  14. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-51a170133a154190b896552921e04adc
Source dataset
uspto-grants-2014_06
Patent number
US08759548B2

Reaction notes

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