Sodium Hydroxide → HCID 90011400, compound

HRID 1481476Notes

Reaction equation

HRID 1481476 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]3[O:14][CH:15]=CC=3)=[CH:11][C:10]([C:18]([F:21])([F:20])[F:19])=[N:9]2)=[N:6][CH:7]=1.FC(F)(F)C(=O)CC(C1OC=CC=1)=O.Cl.BrC1C=C[C:41]([NH:44][NH2:45])=NC=1.[OH-:46].[Na+]>C(O)(=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]3[O:14][C:15](=[O:46])[N:44]([CH3:41])[N:45]=3)=[CH:11][C:10]([C:18]([F:19])([F:20])[F:21])=[N:9]2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 675944,4,4-Trifluoro-1-(2-furanyl)-1,3-butanedioneHCID 90010651HCID 90010651, compoundHCID 90011365HCID 90011365, compound

Product 1

HCID 90011400HCID 90011400, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Step-1: 5-Bromo-2-(5-(furan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)pyridine: A mixture of 4,4,4-trifluoro-1-(furan-2-yl)butane-1,3-dione (7.0 g, 34.0 mmol) and 5-bromo-2-hydrazinylpyridine hydrochloride (7.62 g, 34.0 mmol) in acetic acid (20 mL) was stirred at 70° C. for 1.5 h. The reaction mixture was cooled to room temperature (RT) and then diluted with ethyl acetate (200 mL) and basified with aqueous sodium hydroxide solution (10%, pH 7-8). The resulting slurry was filtered and the filtrate was washed with water (50 mL), dried (Na2SO4) and filtered. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography (silica gel, 20% ethyl acetate-hexanes as eluent) to afford 10 g (82%) of the title compound as white semisolid. 1HNMR (400 MHz, CDCl3) δ 8.54 (brs, 1H), 8.02 (dd, J=2.5 & 8.5 Hz, 1H), 7.64 (d, J=8.5 Hz, 1H), 7.45 (d, J=1.5 Hz, 1H), 6.93 (s, 1H), 6.62 (d, J=3.5 Hz, 1H), 6.47 (dd, J=3.5 & 1.5 Hz, 1H); ESI-MS (m/z) 358, 360 [(MH)+, Br79,81].

Workup

  1. temperatureThe reaction mixture was cooled to room temperature (RT)
  2. filtrationThe resulting slurry was filtered
  3. washthe filtrate was washed with water (50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customThe filtrate was rotary evaporated
  7. customthe crude product was purified by flash column chromatography (silica gel, 20% ethyl acetate-hexanes as eluent)

Sources & evidence

ORD record
ord-43321c64833748c38e82fe0c76a56f61
Source dataset
uspto-grants-2016_08
Patent number
US09409898B2

Reaction notes

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