Ethylene Glycol → 2-hydroxyethyl 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylate

HRID 1402517ノート

反応式

HRID 1402517 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:33]=[CH:32][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]3[NH:28][CH:27]=[C:26]([C:29]([OH:31])=[O:30])[CH:25]=3)[CH:19]=2)=[CH:15][CH:14]=1)=[O:11].[CH2:34](O)[CH2:35][OH:36].O.Cl>CN(C)C1C=CN=CC=1.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:14]=[CH:15][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]3[NH:28][CH:27]=[C:26]([C:29]([O:31][CH2:34][CH2:35][OH:36])=[O:30])[CH:25]=3)[CH:19]=2)=[CH:32][CH:33]=1)=[O:11]

参加物

7

反応物 4

HCID 174Ethylene GlycolHCID 313Hydrochloric AcidHCID 962WaterHCID 510012875-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid

生成物 1

HCID 670425122-hydroxyethyl 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylate

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

A mixture of 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylic acid (50 mg, 0.11 mmol), ethylene glycol (1 ml), 1-Ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (EDC.HCl, 25 mg, 0.13 mmol) and 4-dimethylaminopyridine (DMAP, 5 mg, 0.04 mmol) in anhydrous THF (10 ml) was stirred at 60° C. for 16 hours. The mixture was poured into 100 ml of water. 2M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give the crude, which was purified by silica gel chromatography with a gradient of 3-5% MeOH/CHCl3 to give 2-hydroxyethyl 5-{4-[4-({[(2-fluoro-5-methylphenyl)amino]carbonyl}amino)phenoxy]pyridin-2-yl}-1H-pyrrole-3-carboxylate as white solid. Yield: 36 mg, 67%.

後処理

  1. filtrationThe precipitates were filtered
  2. washwashed with water
  3. customdried in vacuo
  4. customto give the crude, which
  5. customwas purified by silica gel chromatography with a gradient of 3-5% MeOH/CHCl3

出典と根拠

ORDレコード
ord-ef9a3b991db647e0972ce48246be5ccb
出典データセット
uspto-grants-2014_12
特許番号
US08906944B2

反応ノート

読み込み中…