3-(Chloromethyl)pyridine → HCID 14209197, compound

HRID 1199036Notes

Reaction equation

HRID 1199036 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.Cl[CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1>CN(C)C=O.C1(C)C=CC=CC=1>[CH3:25][O:24][C:18]1[N:17]=[C:16]2[C:21]([CH:22]=[CH:23][C:14]([N:5]3[CH:4]([O:3][CH2:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[C:12]4[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=4)[C:6]3=[O:13])=[N:15]2)=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 183583-(Chloromethyl)pyridineHCID 24758Sodium hydrideHCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

Product 1

HCID 14209197HCID 14209197, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

An oily suspension (50% by weight; 1.2 g) of sodium hydride is added in small portions at a temperature in the region of 0° C. to a solution, maintained under an argon atmosphere, of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (6.2 g) in anhydrous dimethylformamide (100 cc). The suspension obtained is stirred for 30 minutes at a temperature in the region of 0° C. and a 1.4M solution (16 cc) of 3-chloromethylpyridine in toluene is then added. The reaction mixture is heated with stirring to a temperature of 70° C. for 1 hour, then cooled to a temperature in the region of 10° C., poured into distilled water (600 cc) and extracted with dichloromethane (3×200 cc). The organic phases are combined, washed with distilled water (4×50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 1N aqueous hydrochloric acid solution (30 cc) is added to the residue obtained. After removal of a solid by filtration, the filtrate is alkalinized with 10N aqueous sodium hydroxide solution to a pH in the region of 11, and extracted with dichloromethane (3×150 cc). The organic phases are combined, washed with distilled water (3×25 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in acetonitrile, 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-[(3-pyridyl)methoxy]-1-isoindolinone (3.7 g), m.p. 175° C., is obtained.

Workup

  1. customThe suspension obtained
  2. temperatureThe reaction mixture is heated
  3. stirringwith stirring to a temperature of 70° C. for 1 hour
  4. temperaturecooled to a temperature in the region of 10° C.
  5. additionpoured
  6. distillationinto distilled water (600 cc)
  7. extractionextracted with dichloromethane (3×200 cc)
  8. washwashed with distilled water (4×50 cc)
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  12. addition1N aqueous hydrochloric acid solution (30 cc) is added to the residue
  13. customobtained
  14. customAfter removal of a solid
  15. filtrationby filtration
  16. extractionextracted with dichloromethane (3×150 cc)
  17. washwashed with distilled water (3×25 cc)
  18. dry with materialdried over magnesium sulphate
  19. filtrationfiltered
  20. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  21. customAfter recrystallization in acetonitrile

Sources & evidence

ORD record
ord-71e74a2b31a94df4b45da3d166f1da0f
Source dataset
uspto-grants-1990_02
Patent number
US04898871

Reaction notes

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