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4-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (2-hydroxy-1,1-dimethylethoxy)-amide

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title compound

수율 11.0%

4-(2-Fluoro-4-iodophenylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (2-hydroxy-1,1-dimethylethoxy)amide

수율 11.0%

용매

TFA

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후처리

1. 1
   농축The reaction mixture was concentrated in vacuo
2. 2
   workup.DISSOLUTIONthe resultant residue was dissolved in dichloromethane (10 mL)
3. 3
   세척methanol (2 mL) before being washed with aqueous saturated sodium bicarbonate solution (3×10 mL)
4. 4
   추출The aqueous layer was extracted with dichloromethane (2×10 mL)
5. 5
   여과the combined organic extracts filtered through a hydrophobic frit
6. 6
   농축then concentrated in vacuo
7. 7
   기타The resultant residue was purified by reverse-phase HPLC (gradient 10-95% methanol/water+0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm)

실험 절차

4-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (2-hydroxy-1,1-dimethylethoxy)-amide (420 mg, 0.69 mmol) was dissolved in TFA (5 mL) and the reaction mixture heated at 65° C. for 3 hours. The reaction mixture was concentrated in vacuo and the resultant residue was dissolved in dichloromethane (10 mL) and methanol (2 mL) before being washed with aqueous saturated sodium bicarbonate solution (3×10 mL). The aqueous layer was extracted with dichloromethane (2×10 mL) and the combined organic extracts filtered through a hydrophobic frit then concentrated in vacuo. The resultant residue was purified by reverse-phase HPLC (gradient 10-95% methanol/water+0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm) to yield the title compound as a white solid (21 mg, 11%). LCMS (Method A): RT=7.71 min, [M+H]+=486. 1H NMR (DMSO-d6, 400 MHz) 13.53 (1H, s), 11.20 (1H, s), 10.15 (1H, s), 8.49 (1H, s), 7.80 (1H, d, J=9.68 Hz), 7.63 (1H, d, J=8.38 Hz), 7.25 (1H, t, J=8.38 Hz), 6.70 (1H, s), 4.65 (1H, s), 1.17 (6H, s).

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