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Water → 2-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate

HRID 1029476
ノート
印刷プレビュー

反応式

HRID 1029476 の反応式
[CH3:1][CH:2]([CH3:8])[CH2:3][CH2:4][C:5]([OH:7])=[O:6].N12CCCN=C1CCCCC2.Cl[CH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[N:22]1[C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[N:34][C:35]([Cl:41])=[CH:36][CH:37]=2)[N:32]=1.O>CN(C)C=O.ClCCl>[CH3:1][CH:2]([CH3:8])[CH2:3][CH2:4][C:5]([O:7][CH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[N:22]1[C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[N:34][C:35]([Cl:41])=[CH:36][CH:37]=2)[N:32]=1)=[O:6]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 962WaterHCID 12587Isocaproic acidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 141824043-Chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone

生成物 1

HCID 141824072-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate収率 48.8%

試薬・触媒・溶媒 2

HCID 6228
Dimethylformamide
溶媒
HCID 6344Dichloromethane溶媒

反応条件

温度
20 °C

実験手順

4-Methylpentanoic acid (2.4 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (3.05 g) are added at a temperature in the region of 20° C. to a solution, maintained under an argon atmosphere, of 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (6.6 g) in anhydrous dimethylformamide (60 cc), and the suspension obtained is stirred for 24 hours at a temperature in the region of 20° C. Distilled water (500 cc) and dichloromethane (150 cc) are then added. The aqueous phase is separated after settling has occurred and then re-extracted with dichloromethane (2×150 cc). The organic phases are combined, washed with distilled water (3×50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. The oily residue is purified by chromatography on silica gel (150 g) contained in a column 3.5 cm in diameter [eluant: dichloromethane/methanol (98.2 by volume)]. Elution is first performed with 200 cc of solvent: the corresponding eluate is discarded; elution is then performed with 900 cc of solvent: the corresponding eluate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in ethanol, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate (4 g), m.p. 147° C., is obtained.

後処理

  1. customthe suspension obtained
  2. customThe aqueous phase is separated after settling
  3. extractionre-extracted with dichloromethane (2×150 cc)
  4. washwashed with distilled water (3×50 cc)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 60° C
  8. customThe oily residue is purified by chromatography on silica gel (150 g)
  9. washElution
  10. washelution
  11. concentrationthe corresponding eluate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  12. customAfter recrystallization in ethanol

出典と根拠

ORDレコード
ord-53a26d1e8c9b446bac8da6ae45058760
出典データセット
uspto-grants-1992_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US05102890

反応ノート

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