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

HRID 475034

반응식

HRID 475034 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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=11.2 Hz), 8.72 (s, 1H), 8.13 (d, 1H, J=8.0 Hz), 7.87-7.90 (m, 2H), 7.76-7.78 (m, 2H), 7.41 (dd, 1H, J=8.0, 11.2 Hz), 6.73 (d, 1H, J=9.6 Hz), 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).

후처리

  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)

출처 및 근거

ORD 기록
ord-b94f1ef394ad45fe9e5fa67dceefc8ef
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637545B2

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