5-Methyl-2-hexanone → 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone

HRID 1087775

Reaction equation

HRID 1087775 reaction equation
[H-].[Na+].O[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.[CH3:26][CH:27]([CH3:33])[CH2:28][CH2:29][C:30](=[O:32])[CH3:31]>CN(C)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]([CH2:31][C:30](=[O:32])[CH2:29][CH2:28][CH:27]([CH3:33])[CH3:26])[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

Participants

5

Reactant 3

HCID 80345-Methyl-2-hexanoneHCID 24758Sodium hydrideHCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

Product 1

HCID 141821822-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinoneYield 61.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-5 °C

Procedure

An oily suspension (50% by weight; 0.5 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 (1.6 g) in anhydrous dimethylformamide (20 cc), and the suspension obtained is stirred for 30 minutes at a temperature in the region of -5° C. A solution of 5-methyl-2-hexanone (1.2 g) in anhydrous dimethylformamide (5 cc) is then added and stirring is continued for 5 hours at a temperature in the region of 20° C. The reaction mixture is then poured into distilled water (200 cc) and extracted with dichloromethane (3×100 cc). The organic phases are combined, washed with distilled water (5×20 cc) and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The oily residue obtained is purified by chromatography on silica gel (15 g) contained in a column 1.5 cm in diameter [eluent: dichloromethane/methanol (99:1 by volume)]. Elution is first performed with 30 cc of solvent: the corresponding eluate is discarded; elution is then performed with 100 cc of solvent: the corresponding eluate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The residue obtained is recrystallized in ethyl acetate; 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone (1.3 g), m.p. 150° C., is thereby obtained.

Workup

  1. customthe suspension obtained
  2. stirringstirring
  3. waitis continued for 5 hours at a temperature in the region of 20° C
  4. additionThe reaction mixture is then poured
  5. distillationinto distilled water (200 cc)
  6. extractionextracted with dichloromethane (3×100 cc)
  7. washwashed with distilled water (5×20 cc)
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  9. customThe oily residue obtained
  10. customis purified by chromatography on silica gel (15 g)
  11. washElution
  12. washelution
  13. concentrationthe corresponding eluate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  14. customThe residue obtained
  15. customis recrystallized in ethyl acetate

Sources & evidence

ORD record
ord-9d1556d47bf24276a5648431f0cddca4
Source dataset
uspto-grants-1990_10
Patent number
US04960779

Linked notes

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