Triethylamine → 4-(1-(4-methoxybenzyl)-3-vinyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine

HRID 2241259Notes

Reaction equation

HRID 2241259 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[CH:29]([B-](F)(F)F)=[CH2:30].[K+].C(N(CC)CC)C>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].C(O)CC>[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([CH:29]=[CH2:30])=[N:9]2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 23679353Potassium vinyltrifluoroborateHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

Product 1

HCID 685144684-(1-(4-methoxybenzyl)-3-vinyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamineYield 64%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (3.68 g, 7.50 mmol, prepared according to the procedure for Example 7, Step B), potassium vinyltrifluoroborate (2.01 g, 15.0 mmol), triethylamine (2.08 ml, 15.0 mmol) and n-propanol (20 mL) was sparged with N2 for 5 min, and then Pd(dppf)Cl2 (0.306 g, 0.375 mmol) was added. The reaction was heated at 100° C. for 3 hours in a sealed vessel. After cooling to ambient temperature, the reaction was concentrated in vacuo. The residue was partitioned between DCM (30 mL) and water (30 mL). The phases were separated, and the aqueous phase was re-extracted with DCM (2×10 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified by Biotage Flash 65 chromatography system, eluting with 20% EtOAc/hexanes (1 L), 1:1 EtOAc/hexanes (1 L), then 2:1 EtOAc/hexanes (2 L). The product was obtained as a reddish colored solid (2.00 g, 64%).

Workup

  1. customprepared
  2. customwas sparged with N2 for 5 min
  3. temperatureAfter cooling to ambient temperature
  4. concentrationthe reaction was concentrated in vacuo
  5. customThe residue was partitioned between DCM (30 mL) and water (30 mL)
  6. customThe phases were separated
  7. extractionthe aqueous phase was re-extracted with DCM (2×10 mL)
  8. dry with materialThe combined organic phases were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude was purified by Biotage Flash 65 chromatography system
  12. washeluting with 20% EtOAc/hexanes (1 L), 1:1 EtOAc/hexanes (1 L)

Sources & evidence

ORD record
ord-165f22d140bd4700a29981b5d7de95ee
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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