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

HRID 1029481Notes

Reaction equation

HRID 1029481 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][C:10]1[N:19]=[C:18]2[C:13]([CH:14]=[CH:15][C:16]([N:20]3[CH:28]([OH:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:21]3=[O:30])=[N:17]2)=[CH:12][CH:11]=1.[CH3:31][CH:32]([CH3:38])[CH2:33][CH2:34][C:35](Cl)=[O:36].O>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:31][CH:32]([CH3:38])[CH2:33][CH2:34][C:35]([O:30][CH:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:28](=[O:29])[N:20]1[C:16]1[CH:15]=[CH:14][C:13]2[C:18](=[N:19][C:10]([O:9][CH3:8])=[CH:11][CH:12]=2)[N:17]=1)=[O:36]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 170008Pentanoyl chloride, 4-methyl-HCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

Product 1

HCID 700566582-(7-Methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoateYield 30.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (27 cc) is added to a solution, maintained at a temperature in the region of 20° C., of 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone (12.3 g) in methylene chloride (200 cc). 4-Methylpentanoyl chloride (10.8 g) and 4-dimethylaminopyridine (50 mg) are then introduced dropwise in the course of 20 minutes, and the reaction mixture is then heated for 19 hours under reflux. The suspension obtained in poured into water (800 cc) and the solid obtained is separated by filtration and removed. The organic phase is separated after settling has occurred, washed with water, dried and concentrated to dryness under reduced pressure (2.7 kPa). The oily residue obtained is purified by chromatography on silica gel (0.063-0.2 mm; 150 g) contained in a column 2.7 cm in diameter (eluant: methylene chloride), eluting 50-cc fractions. Fractions 6 to 18 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After the solid obtained has been recrystallized in acetonitrile, 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate (4.9 g), m.p. 133° C., is obtained.

Workup

  1. temperaturethe reaction mixture is then heated for 19 hours
  2. temperatureunder reflux
  3. customThe suspension obtained
  4. customthe solid obtained
  5. customis separated by filtration
  6. customremoved
  7. customThe organic phase is separated after settling
  8. washwashed with water
  9. customdried
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe oily residue obtained
  12. customis purified by chromatography on silica gel (0.063-0.2 mm; 150 g)
  13. washeluting 50-cc fractions
  14. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  15. customAfter the solid obtained
  16. customhas been recrystallized in acetonitrile

Sources & evidence

ORD record
ord-6f424b40573e43d990b09dc9d2e26c4b
Source dataset
uspto-grants-1992_04
Patent number
US05102890

Reaction notes

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