Iodine → 6-iodo-3-styryl-1-[2-(trimethyl-silanyl)ethoxymethyl]-1H-indazole

HRID 1861078Notes

Reaction equation

HRID 1861078 reaction equation
[CH:1]([C:9]1[C:17]2[C:12](=[CH:13][C:14](N)=[CH:15][CH:16]=2)[N:11]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[N:10]=1)=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.N([O-])=O.[Na+].[I:31]I>CC(O)=O.O.Cl>[I:31][C:14]1[CH:13]=[C:12]2[C:17]([C:9]([CH:1]=[CH:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)=[N:10][N:11]2[CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 807IodineHCID 23668193Sodium NitriteHCID 693709803-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-ylamine

Product 1

HCID 693701476-iodo-3-styryl-1-[2-(trimethyl-silanyl)ethoxymethyl]-1H-indazoleYield 113.7%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent3×

Conditions

Temperature
2 °C

Procedure

To a solution of 3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-ylamine (1.58 g, 4 mmol) in AcOH (14 mL), water (3 mL) and concentrated HCl (1.67 mL) cooled to 2° C. was added a solution of NaNO2 (304 mg, 4.4 mmol) in water (0.5 mL) over 5 min. The resulting dark red solution was stirred at 2° C. for 0.5 h, then a solution of KI (797 mg, 4.8 mmol) and I2 (610 mg, 2.4 mmol) in water (1 mL) was added drop-wise so as to keep the internal temperature below 5° C. After 2 h at 2° C. the reaction was allowed to stir at 23° C. for 17 h. The reaction was quenched with 3 N NaOH (aq), diluted with EtOAc (50 mL) and H2O (15 mL), the phases were separated and the aqueous was extracted 2×15 mL EtOAc. The pooled organic phase was washed 3×20 mL 5% NaHSO3, brine (15 mL), dried with Na2SO4, decanted and concentrated under reduced pressure. The crude reaction was purified by silica gel chromatography (eluting with 1:1 hexane:EtOAc) to give 6-iodo-3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazole as a white solid (1.3 g, 68% yield). 1H NMR (300 MHz, CDCl3) δ 8.03 (s, 1H), 7.79 (d, 1H, J=9.0 Hz), 7.30-7.60 (m, 8H), 5.73 (s, 2H), 3.63 (t, 2H, J=6.0 Hz), 0.96 (t, 2H, J=6.0 Hz), 0.0 (s, 9); 13C NMR (75 MHz, CDCl3) δ 143.6, 142.4, 137.2, 132.1, 130.8, 129.0, 128.3, 126.8, 122.5, 122.4, 119.6, 119.5,92.9, 78.1,66.9, 18.0, −1.2. Anal. Calc'd: C, 52.94; H, 5.29; N, 5.88. Found: C, 52.66; H, 5.29; N, 5.74.

Workup

  1. customthe internal temperature below 5° C
  2. waitAfter 2 h at 2° C. the reaction was allowed
  3. stirringto stir at 23° C. for 17 h
  4. customThe reaction was quenched with 3 N NaOH (aq)
  5. additiondiluted with EtOAc (50 mL) and H2O (15 mL)
  6. customthe phases were separated
  7. extractionthe aqueous was extracted 2×15 mL EtOAc
  8. washThe pooled organic phase was washed 3×20 mL 5% NaHSO3, brine (15 mL)
  9. dry with materialdried with Na2SO4
  10. customdecanted
  11. concentrationconcentrated under reduced pressure
  12. customThe crude reaction
  13. customwas purified by silica gel chromatography (eluting with 1:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-fb90b4f589c84c67aaece47bd0b3a2b8
Source dataset
uspto-grants-2003_03
Patent number
US06531491B1

Reaction notes

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