Reaction #166251

Reaction equation

4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid

O-methyl-hydroxylamine

EDCI

HOBt

DIPEA

→

title compound

Yield 44.0%

4-(2-Fluoro-4-iodo-phenylamino)-1H-indazole-5-carboxylic acid methoxy-amide

Yield 44.0%

Solvents

ethyl acetate

DMF

Conditions

Workup

1. 1
   Washwashed with saturated aqueous sodium hydrogen carbonate
2. 2
   Dryingwater, dried (Na2SO4)
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated in vacuo
5. 5
   OtherThe resultant solid was triturated with a solution of hot methanol/water/NaHCO3
6. 6
   Filtrationthe solid filtered off
7. 7
   Washwashed with water

Procedure

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (70 mg, 0.176 mmol) and O-methyl-hydroxylamine (19 mg, 0.21 mmol) in DMF (2 mL) was added EDCI (40 mg, 0.21 mmol), HOBt (28 mg, 0.21 mmol) and DIPEA (70 μL, 0.42 mmol). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate then water, dried (Na2SO4), filtered and concentrated in vacuo. The resultant solid was triturated with a solution of hot methanol/water/NaHCO3, the solid filtered off, washed with water to give the title compound as a pale pink solid (33 mg, 44%). LCMS (Method A): RT=9.09 min, [M+H]+=427. 1H NMR (DMSO-d6, 400 MHz) 13.20 (1 H, s), 11.62 (1 H, s), 9.99 (1 H, s), 7.66 (1 H, dd, J=10.33, 1.94 Hz), 7.46-7.40 (2 H, m), 7.23 (1 H, s), 7.01 (1 H, d, J=8.78 Hz), 6.92 (1 H, t, J=8.66 Hz), 3.64 (3 H, s).

Source