Sodium hydride → HCID 19867666, compound

HRID 1199043Notes

Reaction equation

HRID 1199043 reaction equation
[OH:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[N:15][C:16]([O:22][CH3:23])=[CH:17][CH:18]=2)[N:13]=1.[H-].[Na+].Cl[CH2:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29]>CN(C)C=O>[CH3:23][O:22][C:16]1[N:15]=[C:14]2[C:19]([CH:20]=[CH:21][C:12]([N:3]3[CH:2]([O:1][CH2:27][C:28]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[O:29])[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[C:4]3=[O:11])=[N:13]2)=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74040Morpholine, 4-(chloroacetyl)-HCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

Product 1

HCID 19867666HCID 19867666, compoundYield 11.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The procedure is as in Example 26, but starting with 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (12.3 g) in dimethylformamide (150 cc), an oily suspension (50% by weight; 2.4 g) of sodium hydride and N-chloroacetylmorpholine (8.2 g). The residue obtained is purified initially by chromatography on silica (0.063-0.2 mm; 180 g) contained in a column 4 cm in diameter [eluant: methylene chloride/methanol mixture (95:5 by volume)], collecting 100-cc fractions. Fractions 190 to 210 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is purified again by flash chromatography on silica (0.040-0.063 mm; 82 g) contained in a column 3 cm in diameter (eluant: methylene chloride/methanol [98:2 by volume)], collecting 10-cc fractions. Fractions 220 to 235 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. The solid obtained is recrystallized successively in acetonitrile and in ethanol. 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(2-morpholino-2-oxoethoxy)-1-isoindolinone (2 g), m.p. 192° C., is thereby obtained.

Workup

  1. customThe residue obtained
  2. customis purified initially by chromatography on silica (0.063-0.2 mm; 180 g)
  3. customcollecting 100-cc fractions
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue obtained
  6. customis purified again by flash chromatography on silica (0.040-0.063 mm; 82 g)
  7. custommethylene chloride/methanol [98:2 by volume)], collecting 10-cc fractions
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  9. customThe solid obtained
  10. customis recrystallized successively in acetonitrile and in ethanol

Sources & evidence

ORD record
ord-8cd77f88a4e24e208cf866473efa5545
Source dataset
uspto-grants-1990_02
Patent number
US04898871

Reaction notes

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