Water → [2-(7-methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyloxy]-N-cyclohexylacetamide

HRID 1199039Notes

Reaction equation

HRID 1199039 reaction equation
[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.[CH:26]1([NH:32][C:33](=[O:36])[CH2:34]Cl)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.O>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[C:4](=[O:3])[C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[CH:6]3[O:13][CH2:34][C:33]([NH:32][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:36])=[N:15]2)=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2223652-Chloro-N-cyclohexylacetamideHCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

Product 1

HCID 19867698[2-(7-methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyloxy]-N-cyclohexylacetamideYield 10.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

An oily suspension (50% by weight; 2.1 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 (12.3 g) in anhydrous dimethylformamide (150 cc). The suspension obtained is stirred for 45 minutes at a temperature in the region of 0° C., N-(cyclohexyl)chloroacetamide (7.7 g) is then added and the mixture is heated to 80° C. for 18 hours. After being cooled, the reaction mixture is poured into water (700 cc) and the precipitate obtained is separated by filtration, washed with water and dried in the air. The solid obtained is purified by chromatography on silica (0.063-0.2 mm; 220 g) contained in a column 4 cm in diameter (eluant: methylene chloride), collecting 50-cc fractions. Fractions 41 to 60 are combined and concentrated to dryness under reduced pressure (2.7 kPa). By recrystallization of the residue obtained in acetonitrile, [2-(7-methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyloxy]-N-cyclohexylacetamide (1.8 g), m.p. 175° C., is obtained.

Workup

  1. customThe suspension obtained
  2. additionis then added
  3. temperatureAfter being cooled
  4. customthe precipitate obtained
  5. customis separated by filtration
  6. washwashed with water
  7. customdried in the air
  8. customThe solid obtained
  9. customis purified by chromatography on silica (0.063-0.2 mm; 220 g)
  10. customcollecting 50-cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  12. customBy recrystallization of the residue
  13. customobtained in acetonitrile

Sources & evidence

ORD record
ord-e63d39b71d804fb0bbc196a182820031
Source dataset
uspto-grants-1990_02
Patent number
US04898871

Reaction notes

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