Tri-o-tolylphosphine → HCID 69353211, compound

HRID 1827483Notes

Reaction equation

HRID 1827483 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[CH:10]([C:12]1[C:20]2[C:15](=[CH:16][C:17]([N+:21]([O-:23])=[O:22])=[CH:18][CH:19]=2)[N:14]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[N:13]=1)=[CH2:11].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:8][C:6]1[CH:5]=[C:4]([CH3:9])[N:3]=[C:2]([CH:11]=[CH:10][C:12]2[C:20]3[C:15](=[CH:16][C:17]([N+:21]([O-:23])=[O:22])=[CH:18][CH:19]=3)[N:14]([CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)[N:13]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 149751952-Bromo-4,6-dimethylpyridineHCID 22136521HCID 22136521, compound

Product 1

HCID 69353211HCID 69353211, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 2-bromo-4,6-dimethylpyridine (2.42 g, 13 mmol), 3-vinyl-6-nitro-1-(tetrahydro -pyran-2-yl)-1H-indazole (2.37 g, 8.67 mmol), palladium acetate (0.145 g, 0.65 mmol), tri-ortho-tolylphosphine (0.791 g, 2.6 mmol), and diisopropylethylamine (2.4 mL, 13.8 mmol) in aqueous DMF (85%, 34.5 mL) was degassed with Argon bubbling for 5 minutes followed by sonication for 5 minutes before heating in microwave apparatus (300 watts, 10% power) at 110° C. for 40 minutes. After cooling, the mixture was dropped into cold water. The resulting yellow ppt was collected by filtration. The solids were dissolved in ethyl acetate, dried (sodium sulfate), and concentrated under reduced pressure. The residue was purified on silica gel using a gradient of 0 to 20% ethyl acetate in a mixture of chloroform and hexanes (1:1) as eluent. Product from chromatography was triturated with MTBElhexanes to obtain clean product as yellow solid. Mother liquor was repurified in a similar fashion on silica gel followed by trituration to obtain product in a 68% yield. 1H NMR (CDCl3): δ 8.54 (1H, s), 8.15 (1H, d, J=9.4 Hz), 8.08 (1H, dd, J=9.04,1.9 Hz), 7.87 (1H, d, J=16.6 Hz), 7.55 (1H, d, J=16.6 Hz), 7.14 (1H, s), 6.90 (1H, s), 5.82 (1H, dd, J=9.0, 3.0 Hz), 4.08–4.01 (1H, m), 3.84–3.76 (1H, m), 2.56 (3H, s), 2.62–2.54 (1H, m), 2.34 (3H, s), 2.24–2.10 (2H, m), 1.88–1.68 (3H, m).

Workup

  1. customwas degassed with Argon bubbling for 5 minutes
  2. customfollowed by sonication for 5 minutes
  3. temperatureAfter cooling
  4. additionthe mixture was dropped into cold water
  5. filtrationThe resulting yellow ppt was collected by filtration
  6. dissolutionThe solids were dissolved in ethyl acetate
  7. dry with materialdried (sodium sulfate)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified on silica gel using a gradient of 0 to 20% ethyl acetate
  10. additionin a mixture of chloroform and hexanes (1:1) as eluent
  11. customProduct from chromatography was triturated with MTBElhexanes
  12. customto obtain clean product as yellow solid
  13. customMother liquor was repurified in a similar fashion on silica gel
  14. customto obtain product in a 68% yield

Sources & evidence

ORD record
ord-8e95db78596e43fa8b1e9efe0a33d9d2
Source dataset
uspto-grants-2006_05
Patent number
US07053107B2

Reaction notes

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