4-[acetyl(methyl)amino]butanoic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The procedure is as in Example 1, but starting with 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (9.9 g) in anhydrous dimethylformamide (100 cc), 4-(N-methylacetamido)butanoic acid (4.8 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (4.6 g). The oily residue obtained is purified by chromatography on silica (0.063-0.2 mm; 150 g) contained in a column 3 cm in diameter [eluant: methylene chloride/methanol (99:1 by volume)] and collecting 30-cc fractions. Fractions 76 to 175 are concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. and, after crystallization in ethyl ether, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-(N-methylacetamido)butyrate (3.1 g), m.p. 170° C., is obtained. The oily residue obtained is purified by chromatography on silica (0.063-0.2 mm; 150 g) collecting 30-cc fractions Fractions 76 to 175 are concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. after crystallization in ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The procedure is as in Example 1, but starting with 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (9.9 g) in anhydrous dimethylformamide (100 cc), 4-(N-methylacetamido)butanoic acid (4.8 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (4.6 g). The oily residue obtained is purified by chromatography on silica (0.063-0.2 mm; 150 g) contained in a column 3 cm in diameter [eluant: methylene chloride/methanol (99:1 by volume)] and collecting 30-cc fractions. Fractions 76 to 175 are concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. and, after crystallization in ethyl ether, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-(N-methylacetamido)butyrate (3.1 g), m.p. 170° C., is obtained. The oily residue obtained is purified by chromatography on silica (0.063-0.2 mm; 150 g) collecting 30-cc fractions Fractions 76 to 175 are concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. after crystallization in ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The procedure is as in Example 1, but starting with 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (9.9 g) in anhydrous dimethylformamide (100 cc), 4-(N-methylacetamido)butanoic acid (4.8 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (4.6 g). The oily residue obtained is purified by chromatography on silica (0.063-0.2 mm; 150 g) contained in a column 3 cm in diameter [eluant: methylene chloride/methanol (99:1 by volume)] and collecting 30-cc fractions. Fractions 76 to 175 are concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. and, after crystallization in ethyl ether, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-(N-methylacetamido)butyrate (3.1 g), m.p. 170° C., is obtained. The oily residue obtained is purified by chromatography on silica (0.063-0.2 mm; 150 g) collecting 30-cc fractions Fractions 76 to 175 are concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. after crystallization in ethyl ether