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

HRID 2241194Notes

Reaction equation

HRID 2241194 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 66.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
10 °C

Procedure

A stirred mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (2.45 g, 5.00 mmol; prepared as in Example 7, Step B), potassium vinyltrifluoroborate (0.804 g, 6.00 mmol), triethylamine (0.693 mL, 5.00 mmol), and n-propanol (20 mL) was sparged with N2 for 5 minutes, and then Pd(dppf)Cl2 (82 mg, 0.10 mmol) was added. The sealed reaction was heated at 10° C. for 2 hours. The product and residual starting material were separated from catalyst and other by-products and re-subjected to the reaction conditions as follows. 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 separated from catalyst and other by-products by Biotage Flash 40, eluting with 20% EtOAc/hexanes then 1:1 EtOAc/hexanes. The product and starting material (1:1 ratio by 1H NMR) was resubjected to the same reaction conditions as above. After 2 hours at 100° C., all starting material had been consumed. After workup and Biotage Flash 40 purification as before, the product was obtained as an off-white solid (1.29 g, 66%). 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J=6 Hz, 1H), 7.33 (d, J=9 Hz, 2H), 7.18 (m, 1H), 7.01 (t, J=9 Hz, 1H), 6.82 (d, J=9 Hz, 2H), 6.52 (m, 2H), 6.34 (m, 1H), 6.23 (m 1H), 5.62 (s, 2H), 5.45 (m, 1H), 3.81 (br s, 2H), 3.76 (s, 3H).

Workup

  1. customwas sparged with N2 for 5 minutes
  2. customThe sealed reaction
  3. customwere separated from catalyst and other by-products
  4. customre-subjected to the reaction conditions
  5. concentrationThe reaction was concentrated in vacuo
  6. customThe residue was partitioned between DCM (30 mL) and water (30 mL)
  7. customThe phases were separated
  8. extractionthe aqueous phase was re-extracted with DCM (2×10 mL)
  9. dry with materialThe combined organic phases were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude was separated from catalyst and other by-products by Biotage Flash 40
  13. washeluting with 20% EtOAc/hexanes
  14. customwas resubjected to the same reaction conditions as above
  15. customall starting material had been consumed
  16. customAfter workup and Biotage Flash 40 purification as before, the product

Sources & evidence

ORD record
ord-a4006d721fc4423d87769d633126fd92
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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