Imidazole → 5-(tert-butyldimethylsilanyloxymethyl)-3-iodo-1-methyl-1H-indazole

HRID 246339Notes

Reaction equation

HRID 246339 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:11][OH:12])[CH:9]=2)[N:4]([CH3:13])[N:3]=1.N1C=CN=C1.[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]>CN(C=O)C>[Si:19]([O:12][CH2:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH3:13])[N:3]=[C:2]2[I:1])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 71280092(3-iodo-1-methyl-1H-indazol-5-yl)methanol

Product 1

HCID 712800155-(tert-butyldimethylsilanyloxymethyl)-3-iodo-1-methyl-1H-indazoleYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-iodo-1-methyl-1H-indazol-5-yl)-methanol (810 mg, 2.81 mmol) in DMF (9 mL) was added imidazole (479 mg, 7.03 mmol) followed by tert-butyldimethylsilyl chloride (466 mg, 3.09 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (2×). The combined organics were washed with water (3×) then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 10% EtOAc/hexanes to afford 732 mg (65%) of 5-(tert-butyldimethylsilanyloxymethyl)-3-iodo-1-methyl-1H-indazole as a pale yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.26-7.34 (m, 2H), 7.17-7.23 (m, 1H), 4.73 (s, 2H), 3.97 (s, 3H), 0.84 (s, 9H), 0.00 (s, 6H).

Workup

  1. customthen quenched with water
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organics were washed with water (3×)
  4. dry with materialthen dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-5e19d02294604e75a45a5b5b34d7991a
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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