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 79055ノート

反応式

HRID 79055 の反応式
[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]

参加物

3

反応物 1

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
65 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e77115f7e5924d199ee5b7e3108071ba
出典データセット
uspto-grants-2014_09
特許番号
US08841462B2

反応ノート

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