Benzyl acetone → HCID 22163833, compound

HRID 1087781Notes

Reaction equation

HRID 1087781 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.[CH2:26]([CH2:33][C:34](=[O:36])[CH3:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>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]([CH2:35][C:34](=[O:36])[CH2:33][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[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 17355Benzyl acetoneHCID 24758Sodium hydrideHCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

Product 1

HCID 22163833HCID 22163833, compoundYield 15.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

An oily suspension (50% by weight; 4.7 g) of sodium hydride is added at a temperature in the region of 0° C. to a solution, maintained under a nitrogen atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (15 g) in anhydrous dimethylformamide (280 cc), and the suspension obtained is stirred for 30 minutes at a temperature in the region of 0° C. A solution of benzylacetone (14.4 g) in anhydrous dimethylformamide (20 cc) is added and stirring is continued for 21 hours at a temperature in the region of 0° C. The reaction mixture is then poured into distilled water (1.5 litres). The pH of the aqueous phase is brought to approximately 5 by adding 4 N aqueous hydrochloric acid solution. The product i$ extracted with methylene chloride (3×500 cc). The organic phases are combined and washed with distilled water (3×80 cc), dried over magnesium sulphate and concentrated to dryness at 40° C. under reduced pressure (2.7 kPa). The oily residue obtained is purified by chromatography under pressure (50 kPa) on silica gel (0.040-0.063 mm; 200 g) contained in a column 2.8 cm in diameter. Elution is performed with methylene chloride, collecting 50-cc fractions. Fractions 9 to 21 are combined and concentrated to dryness at 40° C. under reduced pressure (2.7 kPa). After the solid obtained is recrystallized in ethanol, 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-(2-oxo-4-phenylbutyl)-1-isoindolinone (3.4 g), m.p. 180° C., is obtained.

Workup

  1. customthe suspension obtained
  2. stirringstirring
  3. waitis continued for 21 hours at a temperature in the region of 0° C
  4. additionThe reaction mixture is then poured
  5. distillationinto distilled water (1.5 litres)
  6. additionby adding 4 N aqueous hydrochloric acid solution
  7. extractionThe product i$ extracted with methylene chloride (3×500 cc)
  8. washwashed with distilled water (3×80 cc)
  9. dry with materialdried over magnesium sulphate
  10. concentrationconcentrated to dryness at 40° C. under reduced pressure (2.7 kPa)
  11. customThe oily residue obtained
  12. customis purified by chromatography under pressure (50 kPa) on silica gel (0.040-0.063 mm; 200 g)
  13. washElution
  14. customcollecting 50-cc fractions
  15. concentrationconcentrated to dryness at 40° C. under reduced pressure (2.7 kPa)
  16. customAfter the solid obtained
  17. customis recrystallized in ethanol

Sources & evidence

ORD record
ord-4eef0e7dba524bc78307b7962eec65e6
Source dataset
uspto-grants-1990_10
Patent number
US04960779

Reaction notes

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