Triethylamine → 2-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-(nicotinamido)-3-methylbutanoate

HRID 1525818ノート

反応式

HRID 1525818 の反応式
[NH2:1][C@@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].[OH:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[CH2:16][CH2:15][CH:14]([N:19]2[C:27](=[O:28])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]2=[O:29])[C:13]1=[O:30].[C:31](ON1C(=O)CCC1=O)(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[N:34][CH:33]=1.C(N(CC)CC)C>C(Cl)Cl>[C:31]([NH:1][C@@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[N:34][CH:33]=1.[OH:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[CH2:16][CH2:15][CH:14]([N:19]2[C:20](=[O:29])[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:27]2=[O:28])[C:13]1=[O:30]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 870586Succinimidyl NicotinateHCID 710827542-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-amino-3-methylbutanoate

生成物 1

HCID 710828912-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-(nicotinamido)-3-methylbutanoate収率 95.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

2-(1-(2-hydroxyethyl)-2,6-dioxopiperidin-3-yl)isoindolin-1,3-dione (S)-2-amino-3-methylbutanoate (200 mg) and 2,5-dioxopyrrolidinyl nicotinate (120 mg) were dissolved in DCM (20 mL). The mixture was stirred on a magnetic stirrer at room temperature. Triethylamine (1 mL) was added in one portion and the mixture was allowed to react overnight. The reaction mixture was then poured into DCM (30 mL), washed with saturated sodium bicarbonate solution three times (30 mL/wash) and brine (30 mL), dried with anhydrous magnesium sulfate, and filtered. The solvent was removed by rotary evaporation in vacuo. The crude product was purified by silica gel column chromatography (eluted with chloroform: acetone=5:2) to yield pure title compound (239 mg). 1HNMR (CDCl3, ppm) δ 9.04 (d, 1H, J=11.2Hz), 8.72 (s, 1H), 8.13 (d, 1H, J=8.0Hz), 7.87-7.90 (m, 2H), 7.76-7.78 (m, 2H), 7.41 (dd, 1H, J=8.0, 11.2Hz), 6.73 (d, 1H, J=9.6Hz), 5.86-5.98 (m, 2H), 5.05-5.08 (m, 1H), 3.00-3.15 (m, 1H), 2.80-2.95 (m, 2H), 2.12-2.28 (m, 1H), 2.10-2.20 (m, 2H), 0.97-1.05 (m, 3H), 0.85-0.88 (m, 3H).

後処理

  1. customto react overnight
  2. washwashed with saturated sodium bicarbonate solution three times (30 mL/wash) and brine (30 mL)
  3. dry with materialdried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed by rotary evaporation in vacuo
  6. customThe crude product was purified by silica gel column chromatography (eluted with chloroform: acetone=5:2)

出典と根拠

ORDレコード
ord-e90e9c1a98094177a8d4af06dcc3f788
出典データセット
uspto-grants-2015_07
特許番号
US09085563B2

反応ノート

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