Pyridine → Phthalimidine

HRID 328280Notes

Reaction equation

HRID 328280 reaction equation
Cl[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]([OH:23])[N:5](C1C=CC3C(=NC(Cl)=CC=3)N=1)[C:6]2=O.Cl.ClC(N1CCN(C)CC1)=O.C(N(CC)CC)C.N1C=CC=CC=1>O.C(Cl)Cl>[C:4]1(=[O:23])[C:3]2[C:7](=[CH:8][CH:9]=[CH:10][CH:2]=2)[CH2:6][NH:5]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 30169344-Methylpiperazine-1-carbonyl chloride monohydrochlorideHCID 21444381HCID 21444381, compound

Product 1

HCID 10199PhthalimidineYield 117%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

The procedure followed is as in Example 28, but using 4-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone (2 g.), 4-chlorocarbonyl-1-methyl-piperazine hydrochloride (6.9 g.), triethylamine (6.5 cc., equivalent to 4.7 g.), pyridine (30 cc.) and methylene chloride (200 cc.). When the reaction has ended, the reaction mixture is taken up in water (200 cc.). A precipitate which forms is filtered off. After decanting from the methylene chloride layer, the aqueous layer is extracted with methylene chloride (400 cc.). The combined organic layers are dried over anhydrous sodium sulphate (10 g.). After filtration followed by concentration, the residue is washed with water. The mother liquor is extracted with methylene chloride (100 cc.). After evaporation of the methylene chloride, the residue is chromatographed on silica gel (125 g.), elution being carried out with a mixture of methylene chloride and ethyl acetate (9/1 by volume), and fractions of 50 cc. being collected. Fractions 1 to 21 (1,050 cc.) yield isoindolinone starting material (0.9 g.) and fractions 22 to 25 (200 cc.) yield a product (0.3 g.) which is recrystallised from acetonitrile (6 cc.). This gives 4-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-3-(4-methyl-piperazinyl)-carbonyloxy-1-isoindolinone (0.2 g.), melting at 191°-193° C.

Workup

  1. filtrationA precipitate which forms is filtered off
  2. customAfter decanting from the methylene chloride layer
  3. extractionthe aqueous layer is extracted with methylene chloride (400 cc.)
  4. dry with materialThe combined organic layers are dried over anhydrous sodium sulphate (10 g.)
  5. filtrationAfter filtration
  6. concentrationfollowed by concentration
  7. washthe residue is washed with water
  8. extractionThe mother liquor is extracted with methylene chloride (100 cc.)
  9. customAfter evaporation of the methylene chloride
  10. customthe residue is chromatographed on silica gel (125 g.), elution
  11. additionbeing carried out with a mixture of methylene chloride and ethyl acetate (9/1 by volume), and fractions of 50 cc
  12. custombeing collected

Sources & evidence

ORD record
ord-ad01a84bf49a4217a656b11f92fed019
Source dataset
uspto-grants-1977_04
Patent number
US04016274

Reaction notes

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