Water → 2-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 3-dimethylaminopropionate

HRID 1029475Notes

Reaction equation

HRID 1029475 reaction equation
Cl.[CH3:2][N:3]([CH3:9])[CH2:4][CH2:5][C:6]([OH:8])=[O:7].N12CCCN=C1CCCCC2.Cl[CH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:31])[N:23]1[C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[N:35][C:36]([Cl:42])=[CH:37][CH:38]=2)[N:33]=1.O>CN(C)C=O.ClCCl>[CH3:2][N:3]([CH3:9])[CH2:4][CH2:5][C:6]([O:8][CH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:31])[N:23]1[C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[N:35][C:36]([Cl:42])=[CH:37][CH:38]=2)[N:33]=1)=[O:7]

Participants

7

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 115863273-(Dimethylamino)propanoic acid hydrochlorideHCID 141824043-Chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone

Product 1

HCID 141824052-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 3-dimethylaminopropionateYield 14.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

3-Dimethylaminopropionic acid hydrochloride 9.2 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (16.7 g) are added at a temperature in the region of 20° C. to a solution, maintained under an argon atmosphere, of 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (16.5 g) in anhydrous dimethylformamide (100 cc), and the suspension obtained is stirred for 24 hours at a temperature in the region of 20° C. Distilled water (200 cc) and dichloromethane (200 cc) are then added. The aqueous phase is separated after settling has occurred and then re-extracted with dichloromethane (3×50 cc). The organic phases are combined, washed with distilled water (2×50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 80° C. The residue obtained is dissolved in dichloromethane (100 cc) and the solution extracted with 1N aqueous hydrochloric acid solution (2×100 cc). The aqueous phases are combined, washed with dichloromethane (50 cc), alkalinized with 10 N sodium hydroxide solution to a pH in the region of 11 and extracted with dichloromethane (2×150 cc). The organic phases are combined, washed with distilled water (2×30 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. After the product thereby obtained has been recrystallized twice successively in ethanol, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 3-dimethylaminopropionate (2.9 g), m.p. 150° C., is obtained.

Workup

  1. customthe suspension obtained
  2. customThe aqueous phase is separated after settling
  3. extractionre-extracted with dichloromethane (3×50 cc)
  4. washwashed with distilled water (2×50 cc)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 80° C
  8. customThe residue obtained
  9. extractionthe solution extracted with 1N aqueous hydrochloric acid solution (2×100 cc)
  10. washwashed with dichloromethane (50 cc)
  11. extractionextracted with dichloromethane (2×150 cc)
  12. washwashed with distilled water (2×30 cc)
  13. dry with materialdried over magnesium sulphate
  14. filtrationfiltered
  15. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 60° C
  16. customAfter the product thereby obtained
  17. customhas been recrystallized twice successively in ethanol

Sources & evidence

ORD record
ord-c668dc35100e4074bc2bc4e6cb577736
Source dataset
uspto-grants-1992_04
Patent number
US05102890

Reaction notes

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