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

HRID 1029498Notes

Reaction equation

HRID 1029498 reaction equation
N12CCCN=C1CCCCC2.Cl[CH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[N:14]1[C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[N:26][C:27]([Cl:33])=[CH:28][CH:29]=2)[N:24]=1.Cl.[CH:35]([N:38]([CH:45]([CH3:47])[CH3:46])[CH2:39][CH2:40][CH2:41][C:42]([OH:44])=[O:43])([CH3:37])[CH3:36].O>CN(C)C=O.C(Cl)Cl>[CH:45]([N:38]([CH:35]([CH3:37])[CH3:36])[CH2:39][CH2:40][CH2:41][C:42]([O:44][CH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[N:14]1[C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[N:26][C:27]([Cl:33])=[CH:28][CH:29]=2)[N:24]=1)=[O:43])([CH3:47])[CH3:46]

Participants

7

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 141824043-Chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinoneHCID 867456314-Diisopropylaminobutyric acid hydrochloride

Product 1

HCID 867456302-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-diisopropylaminobutyrateYield 49.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

1,8-Diazabicyclo[5.4.0]undec-7-ene (10.7 g) is added dropwise to a suspension of 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (9.9 g) and 4-diisopropylaminobutyric acid hydrochloride (6.7 g) in dimethylformamide (100 cc), and the mixture is stirred at a temperature in the region of 20° C. for 20 hours. The reaction mixture is then poured into water (130 cc). The solid obtained is separated by filtration and then dissolved in methylene chloride (200 cc). The organic extracts are washed with 0.1 N aqueous hydrochloric acid solution (2×35 cc), 0.5 N aqueous hydrochloric acid solution (35 cc), and then with water (2×35 cc). The organic phase is dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is taken up with methylene chloride (200 cc). The organic phase is washed with saturated aqueous sodium hydrogen carbonate solution (2×50 cc). The organic phase is dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is recrystallized in isopropyl ether. 2-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-diisopropylaminobutyrate (7.1 g), m.p. 118° C., is thereby obtained.

Workup

  1. customThe solid obtained
  2. customis separated by filtration
  3. dissolutiondissolved in methylene chloride (200 cc)
  4. washThe organic extracts are washed with 0.1 N aqueous hydrochloric acid solution (2×35 cc), 0.5 N aqueous hydrochloric acid solution (35 cc)
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe residue obtained
  9. washThe organic phase is washed with saturated aqueous sodium hydrogen carbonate solution (2×50 cc)
  10. dry with materialThe organic phase is dried over magnesium sulphate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  13. customThe residue is recrystallized in isopropyl ether

Sources & evidence

ORD record
ord-f374675e541843e2856edee1bce806f5
Source dataset
uspto-grants-1992_04
Patent number
US05102890

Reaction notes

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