Pyridine → Phthalimidine

Participants

Reaction Steps

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.

Provenance & Evidence