Hydrochloric Acid → 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(4-methyl-2-oxopentyloxy)-1isoindolinone

HRID 1199040ノート

反応式

HRID 1199040 の反応式
[H-].[Na+].[OH:3][CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]1[C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[N:17][C:18]([O:24][CH3:25])=[CH:19][CH:20]=2)[N:15]=1.Cl[CH2:27][C:28](=[O:33])[CH2:29][CH:30]([CH3:32])[CH3:31].Cl>CN(C)C=O.C(OCC)(=O)C.O>[CH3:25][O:24][C:18]1[N:17]=[C:16]2[C:21]([CH:22]=[CH:23][C:14]([N:5]3[CH:4]([O:3][CH2:27][C:28](=[O:33])[CH2:29][CH:30]([CH3:32])[CH3:31])[C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[C:6]3=[O:13])=[N:15]2)=[CH:20][CH:19]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 137209281-Chloro-4-methylpentan-2-oneHCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

生成物 1

HCID 198676522-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(4-methyl-2-oxopentyloxy)-1isoindolinone収率 24.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

An oily suspension (50% by weight; 1.8 g) of sodium hydride is added in small portions at a temperature in the region of -5° C. to a solution, maintained under an argon atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (9.3 g) in anhydrous dimethylformamide (120 cc), and the suspension obtained is stirred for 30 minutes at a temperature in the region of 0° C. 1-Chloro-4-methyl-2-pentanone (8.1 g) is then added dropwise while the temperature is maintained at 0° C., and stirring is continued for a further 1 hour at 0° C. and then for 4 hours at a temperature in the region of 20° C. The reaction mixture is then poured into a mixture of ice (150 g) and water (350 cc), neutralized with 1N hydrochloric acid solution and extracted with dichloromethane (3×250 cc). The organic phases are combined, washed with water (4×75 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The residue obtained is taken up with ethyl acetate (25 cc) and the insoluble product is separated by filtration, washed successively with ethyl acetate (10 cc) and diisopropyl ether (10 cc) and then discarded. The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The residue obtained is purified by chromatography on silica (120 g) contained in a column 3 cm in diameter [eluant: dichloromethane/methanol (98.5:1.5 by volume)]. Elution is first performed with 170 cc of solvent: the corresponding eluate is discarded; elution is then performed with 800 cc of solvent and the corresponding eluate concentrated to dryness under reduced pressure (2.7 kPa). After recrystallization of the residue in ethyl acetate, 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-(4-methyl-2-oxopentyloxy)-1isoindolinone (3 g), m.p. 120° C., is obtained. 1-Chloro-4-methyl-2-pentanone may be prepared by the method described by ASINGER F., et al., Ann. Chem., 1964, 672, 156.

後処理

  1. customthe suspension obtained
  2. temperatureis maintained at 0° C.
  3. stirringstirring
  4. waitis continued for a further 1 hour at 0° C.
  5. waitfor 4 hours at a temperature in the region of 20° C
  6. extractionextracted with dichloromethane (3×250 cc)
  7. washwashed with water (4×75 cc)
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  11. customThe residue obtained
  12. customthe insoluble product is separated by filtration
  13. washwashed successively with ethyl acetate (10 cc) and diisopropyl ether (10 cc)
  14. concentrationThe filtrate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  15. customThe residue obtained
  16. customis purified by chromatography on silica (120 g)
  17. washElution
  18. washelution
  19. concentrationthe corresponding eluate concentrated to dryness under reduced pressure (2.7 kPa)
  20. customAfter recrystallization of the residue in ethyl acetate

出典と根拠

ORDレコード
ord-8902fc1001454cd6b6210839488ec182
出典データセット
uspto-grants-1990_02
特許番号
US04898871

反応ノート

読み込み中…