Triethylamine → 1-((2-methoxy-6-methylpyridin-3-yl)methyl)-4-nitro-3-vinyl-1H-indazole

HRID 79276Notes

Reaction equation

HRID 79276 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[C:16]([O:22][CH3:23])=[N:17][C:18]([CH3:21])=[CH:19][CH:20]=2)[N:3]=1.[CH2:24](N(CC)CC)[CH3:25].[B-](F)(F)(F)C=C.[K+]>C(O)(C)C.O1CCCC1>[CH3:23][O:22][C:16]1[C:15]([CH2:14][N:4]2[C:5]3[C:10](=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][CH:6]=3)[C:2]([CH:24]=[CH2:25])=[N:3]2)=[CH:20][CH:19]=[C:18]([CH3:21])[N:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 23679353Potassium vinyltrifluoroborateHCID 672596093-iodo-1-((2-methoxy-6-methylpyridin-3-yl)methyl)-4-nitro-1H-indazole

Product 1

HCID 672606771-((2-methoxy-6-methylpyridin-3-yl)methyl)-4-nitro-3-vinyl-1H-indazoleYield 52.7%

Reagents, catalysts & solvents 1

HCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 3-iodo-1-((2-methoxy-6-methylpyridin-3-yl)methyl)-4-nitro-1H-indazole (982 mg, 2.31 mmol) in a 4:1 mixture of isopropyl alcohol/tetrahydrofuran (10 mL) was stirred under an argon atmosphere. Argon was bubbled through the solution for 20 minutes. Triethylamine (968 μL, 6.94 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (189 mg, 0.231 mmol) and potassium trifluoro(vinyl)borate (659 mg, 6.94 mmol) were added to the solution. The reaction mixture was heated at 90° C. for 24 hour. The mixture was allowed to cool and then filtered through Celite®, rinsing with ethyl acetate. The filtrate was concentrated under reduced pressure. The material was dissolved in ethyl acetate (50 mL), transferred to a reparatory funnel and washed with water and brine. The solution was dried over sodium sulfate, filtered and concentrated under reduced pressure. The material was purified using column chromatography on silica, eluting with 15-20% ethyl acetate in hexanes to give 1-((2-methoxy-6-methylpyridin-3-yl)methyl)-4-nitro-3-vinyl-1H-indazole (395 mg).

Workup

  1. customArgon was bubbled through the solution for 20 minutes
  2. temperatureto cool
  3. filtrationfiltered through Celite®
  4. washrinsing with ethyl acetate
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. dissolutionThe material was dissolved in ethyl acetate (50 mL)
  7. customtransferred to a reparatory funnel
  8. washwashed with water and brine
  9. dry with materialThe solution was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe material was purified
  13. washeluting with 15-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-deaded45f3d14db78b88fbeca26a0e4d
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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