반응 #166230

반응 방정식

4-(2-fluoro-4-iodo-phenylamino)-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid

EDCI

O-(2-vinyloxy-ethyl)-hydroxylamine

DIPEA

HOBt

→

title compound

수율 66.0%

4-(2-Fluoro-4-iodophenylamino)-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid (2-vinyloxy-ethoxy)-amide

수율 66.0%

용매

DMF

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction stirred for 16 hours
2. 2
   농축before being concentrated in vacuo
3. 3
   workup.DISSOLUTIONThe resultant residue was dissolved in ethyl acetate (10 mL)
4. 4
   세척washed with an aqueous saturated sodium bicarbonate solution (10 mL) before the aqueous fraction
5. 5
   추출was extracted twice with ethyl acetate (2×10 mL)
6. 6
   세척The combined organic extracts were washed with brine (20 mL)
7. 7
   건조dried (MgSO4)
8. 8
   농축concentrated in vacuo

실험 절차

To a solution of 4-(2-fluoro-4-iodo-phenylamino)-1-(toluene-4-sulfonyl)-1H-indazole-5-carboxylic acid (0.58 g, 1.05 mmol) in DMF (10 mL) was added EDCI (0.22 g, 1.1 mmol) followed by HOBt (0.16 g, 1.1 mmol) and the reaction mixture stirred at room temperature for 10 minutes. O-(2-vinyloxy-ethyl)-hydroxylamine (0.12 g, 1.1 mmol) and DIPEA (0.2 mL, 1.1 mmol) were added and the reaction stirred for 16 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (10 mL), washed with an aqueous saturated sodium bicarbonate solution (10 mL) before the aqueous fraction was extracted twice with ethyl acetate (2×10 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-100% ethyl acetate in cyclohexane) to yield the title compound as a pale brown solid (439 mg, 66%). LCMS (Method B): RT=4.40 min, [M+H]+=637.

출처