Methyl iodide → 5-(3-chlorophenoxy)-3-iodo-2-methyl-2H-indazole

HRID 246360Notes

Reaction equation

HRID 246360 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[I:15].[CH3:19]C([O-])(C)C.[K+].CI.ClC1C=C(C=CC=1)OC1C=C2C(=CC=1)N(C)N=C2I>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][C:6]1[CH:14]=[CH:13][C:12]2[C:8](=[C:9]([I:15])[N:10]([CH3:19])[N:11]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 712799945-(3-chlorophenoxy)-3-iodo-1-methyl-1H-indazoleHCID 178478165HCID 178478165, compound

Product 1

HCID 712806155-(3-chlorophenoxy)-3-iodo-2-methyl-2H-indazoleYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(3-chlorophenoxy)-3-iodo-1H-indazole (194 mg, 524 μmol) in THF (5 mL) at 0° C. was added KOtBu (82.2 mg, 733 μmol) and the mixture stirred at 0° C. for 30 min. MeI (104 mg, 45.8 μL, 733 μmol) was added. The reaction mixture was stirred at 0° C. for 30 min then warmed to 25° C. and stirred for 1.5 h. The reaction mixture was quenched with saturated ammonium chloride in water and extracted with dichloromethane. The combined organics were dried over MgSO4 and concentrated to a clear oil, then purified by chromatography (40 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min) to afford the desired less polar 5-(3-chlorophenoxy)-3-iodo-1-methyl-1H-indazole (154 mg, 400 mmol, 77%) as a clear yellow oil. MS (M+H)+=384.8; 1H NMR (CDCl3) δ: 7.38 (d, J=9.1 Hz, 1H), 7.17-7.29 (m, 2H), 7.11 (d, J=2.3 Hz, 1H), 7.06 (dt, J=7.9, 0.9 Hz, 1H), 6.94 (t, J=2.3 Hz, 1H), 6.86 (dd, J=8.3, 2.3 Hz, 1H), 4.12 (s, 3H). The regioisomer, 5-(3-chlorophenoxy)-3-iodo-2-methyl-2H-indazole, (32 mg, 83.2 μmol, 16%) was also obtained as a clear yellow oil.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 30 min
  2. temperaturethen warmed to 25° C.
  3. stirringstirred for 1.5 h
  4. customThe reaction mixture was quenched with saturated ammonium chloride in water
  5. extractionextracted with dichloromethane
  6. dry with materialThe combined organics were dried over MgSO4
  7. concentrationconcentrated to a clear oil
  8. custompurified by chromatography (40 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min)
  9. customto afford the

Sources & evidence

ORD record
ord-cdbdafc4771e45d2a083891b1629818c
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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