HCID 16004839, compound → HCID 16004841, compound

HRID 2101333Notes

Reaction equation

HRID 2101333 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:30])[N:15]([CH2:17][C:18]4[C:19]([C:28]#[N:29])=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)=[CH:4][CH:3]=1>C(O)=O.O.[Pt](=O)=O>[NH2:29][CH2:28][C:19]1[C:18]([CH2:17][N:15]2[C:14](=[O:30])[N:11]3[CH:12]=[CH:13][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)=[C:9]([C:31]4[CH:32]=[CH:33][N:34]=[CH:35][CH:36]=4)[C:10]3=[N:16]2)=[CH:23][CH:22]=[C:21]([C:24]([F:25])([F:27])[F:26])[N:20]=1

Participants

5

Reactant 1

HCID 16004839HCID 16004839, compound

Product 1

HCID 16004841HCID 16004841, compoundYield 14.5%

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalystHCID 284Formic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-((7-(4-chlorophenyl)-3-oxo-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-2(3H)-yl)methyl)-6-(trifluoromethyl)picolinonitrile (51 mg, 0.1 mmol) in formic acid (0.8 mL) and water (0.2 mL) was added platinum (IV) oxide (20 mg). The resulting suspension was stirred at 70° C. for 1 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous Na2CO3, water, then saturated aqueous NaCl, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified using preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 40% to 80% B over 8 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The product was dissolved in EtOAc, washed with saturated aqueous NaHCO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 7.4 mg of the title compound as a yellow powder. HPLC/MS: retention time=2.26 min, [M+H]+=511.0.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with saturated aqueous Na2CO3, water
  5. dry with materialsaturated aqueous NaCl, dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified
  8. washeluted with a linear gradient of 40% to 80% B over 8 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm)
  9. concentrationThe desired fractions were concentrated under reduced pressure
  10. dissolutionThe product was dissolved in EtOAc
  11. washwashed with saturated aqueous NaHCO3 once
  12. dry with materialwater twice, then saturated aqueous NaCl, dried over Na2SO4
  13. customevaporated
  14. dissolutionThe residue was dissolved in acetonitrile
  15. temperaturefrozen

Sources & evidence

ORD record
ord-13233d4f11fb486cbdb6810ba0254f2c
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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