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

HRID 79055노트

반응식

HRID 79055 반응식
[OH:1][C@@H:2]([CH3:35])[CH2:3][O:4][NH:5][C:6]([C:8]1[C:9]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:10]2[CH:16]=[N:15][N:14](CC3C=CC(OC)=CC=3)[C:11]2=[N:12][CH:13]=1)=[O:7]>C(O)(C(F)(F)F)=O>[OH:1][C@@H:2]([CH3:35])[CH2:3][O:4][NH:5][C:6]([C:8]1[C:9]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:10]2[CH:16]=[N:15][NH:14][C:11]2=[N:12][CH:13]=1)=[O:7]

참가 물질

3

반응물 1

HCID 866562434-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ((S)-2-hydroxypropoxy)-amide

생성물 1

HCID 446030824-(2-Fluoro-4-iodophenylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ((S)-2-hydroxypropoxy)-amide수율 27%

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

반응 조건

온도
65 °C

실험 절차

4-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ((S)-2-hydroxypropoxy)-amide (500 mg, 0.85 mmol) was dissolved in TFA (5 mL) and the resulting mixture heated at 65° C. for 3 hours before being concentrated in vacuo. The resultant residue was dissolved in dichloromethane (10 mL) and methanol (2 mL) then stirred vigorously with aqueous saturated sodium bicarbonate solution (20 mL) for 2 hours. The aqueous layer was extracted with dichloromethane (2×10 mL) and the combined organic fractions 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 (106 mg, 27%). LCMS (Method A): RT=7.19 min, [M+H]+=472. 1H NMR (DMSO-d6, 400 MHz) 13.51 (1H, s), 10.37 (1H, s), 8.45 (1H, s), 7.80 (1H, dd, J=9.68, 1.89 Hz), 7.63-7.60 (1H, m), 7.25 (1H, t, J=8.42 Hz), 6.74 (1H, s), 3.88-3.81 (1H, m), 3.73-3.69 (2H, m), 1.05 (3H, d, J=6.34 Hz).

후처리

  1. concentrationbefore being concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in dichloromethane (10 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (2×10 mL)
  4. filtrationthe combined organic fractions filtered through a hydrophobic frit
  5. concentrationthen concentrated in vacuo
  6. customThe 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)

출처 및 근거

ORD 기록
ord-e77115f7e5924d199ee5b7e3108071ba
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841462B2

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