Chloroform → 2-(2,6-Dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5 oxide

HRID 626803Notes

Reaction equation

HRID 626803 reaction equation
[CH2:1](N(CC)CC)[CH3:2].Br[C:9]1[CH:14]=[C:13]([Cl:15])[C:12]([N:16]2[CH:26]=[C:19]3[CH:20]=[N+:21]([O-:25])[CH:22]=[C:23]([F:24])[C:18]3=[N:17]2)=[C:11]([Cl:27])[CH:10]=1.C(Cl)(Cl)Cl>C(O)CC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:15][C:13]1[CH:14]=[C:9]([CH:1]=[CH2:2])[CH:10]=[C:11]([Cl:27])[C:12]=1[N:16]1[CH:26]=[C:19]2[CH:20]=[N+:21]([O-:25])[CH:22]=[C:23]([F:24])[C:18]2=[N:17]1

Participants

6

Reactant 3

HCID 6212ChloroformHCID 8471TriethylamineHCID 677022952-(4-Bromo-2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5 oxide

Product 1

HCID 677008712-(2,6-Dichloro-4-vinylphenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5 oxideYield 62%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 10311-PropanolSolvent

Procedure

Triethylamine (3.5 mL, 25 mmol) was added to a mixture of 2-(4-bromo-2,6-dichlorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5 oxide (1.88 g, 5.0 mmol), potassium vinyl trifluoroborate (1.0 g, 7.5 mmol) and Pd(dppf)Cl2.CHCl3 (408 mg, 0.5 mmol) in propan-1-ol (50 mL) and the reaction mixture was heated at 100° C. for 1.5 hours. The resultant mixture was allowed to cool to room temperature before being partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (4-5% methanol in DCM) to afford the title compound as a beige solid (1.0 g, 62% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.00 (d, J=2.6 Hz, 1H), 8.89 (d, J=1.4 Hz, 1H), 8.35 (dd, J=6.3, 1.5 Hz, 1H), 7.97 (s, 2H), 6.85 (dd, J=17.6, 11.0 Hz, 1H), 6.24 (d, J=17.6 Hz, 1H), 5.60 (d, J=11.0 Hz, 1H).

Workup

  1. custombefore being partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
  2. customThe layers were separated
  3. washthe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography (4-5% methanol in DCM)

Sources & evidence

ORD record
ord-18a2d21afb77416995e123e0e89c73a2
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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