1-(4-methoxybenzyl)-4-(2-fluoro-4-nitrophenoxy)-3-iodo-1H-pyrazolo[3,4-b]pyridine → 3-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

HRID 2241190Notes

Reaction equation

HRID 2241190 reaction equation
[CH3:1][O:2][C:3]1[CH:30]=[CH:29][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]([N+:24]([O-])=O)=[CH:20][C:19]=4[F:27])=[C:11]3[C:10]([I:28])=[N:9]2)=[CH:5][CH:4]=1>CCO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][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:27])=[C:11]3[C:10]([I:28])=[N:9]2)=[CH:29][CH:30]=1

Participants

3

Reactant 1

HCID 672214351-(4-methoxybenzyl)-4-(2-fluoro-4-nitrophenoxy)-3-iodo-1H-pyrazolo[3,4-b]pyridine

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

A stirred mixture of 1-(4-methoxybenzyl)-4-(2-fluoro-4-nitrophenoxy)-3-iodo-1H-pyrazolo[3,4-b]pyridine (10.4 g, 20.0 mmol), stannous chloride-dihydrate (22.6 g, 100.0 mmol), and absolute EtOH (200 mL) was heated to 65° C. for 1.5 hours under N2. After cooling to room temperature, the reaction was concentrated in vacuo, and then diluted with DCM (100 mL) and water (100 mL). Aqueous 2N NaOH was added until the pH of the aqueous phase was in the 11-12 range. The biphasic suspension was filtered through a pad of celite, rinsing with DCM (3×100 mL). The filtered biphase was separated, and the aqueous phase was re-extracted with DCM (3×75 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated. Yield: 7.90 g, 78%. The product was used in the next step without purification. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J=6 Hz, 1H), 7.35 (d, J=9 Hz, 2H), 7.03 (t, J=9 Hz, 1H), 6.83 (d, J=9 Hz, 2H), 6.53 (m, 2H), 6.24 (m, 1H), 5.61 (s, 2H), 3.81 (s, 2H), 3.76 (s, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction was concentrated in vacuo
  3. additiondiluted with DCM (100 mL) and water (100 mL)
  4. additionAqueous 2N NaOH was added until the pH of the aqueous phase
  5. filtrationThe biphasic suspension was filtered through a pad of celite
  6. washrinsing with DCM (3×100 mL)
  7. customThe filtered biphase was separated
  8. extractionthe aqueous phase was re-extracted with DCM (3×75 mL)
  9. dry with materialThe combined organic phases were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe product was used in the next step without purification

Sources & evidence

ORD record
ord-30813002968e4cb2848ced9fa0ab3b5d
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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