반응 #166249

반응 방정식

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

HOBt

EDCI

DIPEA

DMF

→

title compound

수율 26.0%

4-(2-Fluoro-4-iodo-phenylamino)-1H-indazole-5-carboxylic acid (tetrahydro-pyran-4-yloxy)-amide

수율 26.0%

용매

ethyl acetate

반응 조건

후처리

1. 1
   세척washed with saturated aqueous sodium hydrogen carbonate
2. 2
   건조water, dried (Na2SO4)
3. 3
   여과filtered
4. 4
   농축concentrated in vacuo
5. 5
   기타The resultant solid was triturated in methanol
6. 6
   여과the solid filtered off
7. 7
   세척washed with methanol

실험 절차

To a solution of 4-(2-fluoro-4-iodophenylamino)-1H-indazole-5-carboxylic acid (100 mg, 0.252 mmol) in DMF (3 mL) was added 0-(tetrahydro-pyran-4-yl)-hydroxylamine (44 mg, 0.378 mmol), HOBt (37 mg, 0.277 mmol), EDCI (53 mg, 0.277 mmol) and DIPEA (92 μl, 0.529 mmol). The reaction was stirred at room temperature for 70 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 subjected to flash chromatography (Si—PPC, gradient 30-100% ethyl acetate in cyclohexane). The resultant solid was triturated in methanol, the solid filtered off, washed with methanol to yield the title compound (33 mg, 26%). LCMS (Method A): RT=9.27 min, [M+H]+=497. 1H NMR (DMSO-d6, 400 MHz): 13.19 (1 H, s), 11.44 (1 H, s), 9.87 (1 H, s), 7.65 (1 H, dd, J=10.36, 1.95 Hz), 7.48 (1H, d, J=8.77 Hz), 7.44-7.38 (1H, m), 7.28 (1 H, s), 7.03 (1 H, d, J=8.75 Hz), 6.89 (1 H, t, J=8.66 Hz), 4.02-3.93 (1 H, m), 3.84-3.76 (2 H, m), 3.36-3.28 (2 H, m), 1.88-1.81 (2 H, m), 1.51 (2 H, dddd, J=12.96, 9.42, 8.75, 4.11 Hz).

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