Reaction #166253

Reaction equation

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

3-hydroxyazetidine hydrochloride

EDCI

HOBt

DIPEA

→

title compound

Yield 49.0%

[4-(2-Fluoro-4-iodo-phenylamino)-1H-indazol-5-yl]-(3-hydroxy-azetidin-1-yl)-methanone

Yield 49.0%

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 residue was triturated in cyclohexane

Procedure

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (70 mg, 0.176 mmol) and 3-hydroxyazetidine hydrochloride (23 mg, 0.21 mmol) in DMF (1 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 residue was triturated in cyclohexane to give the title compound as a pale tan solid (39 mg, 49%). LCMS (Method A): RT=8.23 min, [M+H]+=453. 1H NMR (DMSO-d6, 400 MHz) 13.17 (1 H, s), 9.55 (1 H, s), 7.63 (1 H, dd, J=10.47, 1.94 Hz), 7.41-7.37 (1 H, m), 7.37 (1 H, s), 7.32 (1 H, d, J=8.69 Hz), 7.05-7.00 (1 H, m), 6.92-6.82 (1 H, m), 5.67 (1 H, d, J=6.13 Hz), 4.44-4.37 (1 H, m), 4.24 (2 H, br, s), 3.83 (2 H, br, s).

Source