反应详情

Potassium carbonate (2.1 g) and sodium iodide (0.1 g) are added to a solution of N-propyl-10-[1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarboxamide, L series (2.16 g), and 2-bromoacetophenone (2.5 g) in acetonitrile (25 cc), and the mixture is brought to reflux with stirring for 4 hours. After cooling, the reaction mixture is filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residue is purified by chromatography on a column (height: 25 cm; diameter: 3.6 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting successively with a mixture (3 liters) of methylene chloride and methanol (95:5 by volume) and then with a mixture (2 liters) of methylene chloride and methanol (90:10 by volume) and collecting 75-cc fractions. Fractions 39 to 66 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The yellow meringue-like residue (0.5 g) is taken up with stirring with isopropyl ether (40 cc) for 1 hour at a temperature in the region of 20° C., drained, washed with isopropyl ether (2×5 cc) and dried under reduced pressure (5 mm Hg; 0.7 kPa) at 40° C. 1-Benzoylmethyl-1-[2-(2-propylcarbamoyl-10-phenothiazinyl)propyl]pyrrolidinium bromide, L series (0.33 g), is thereby obtained in the form of a yellow powder, m.p. about 190° C.

1. temperatureto reflux
2. temperatureAfter cooling
3. filtrationthe reaction mixture is filtered
4. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
5. customThe residue is purified by chromatography on a column (height: 25 cm; diameter: 3.6 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa)
6. washeluting successively with a mixture (3 liters) of methylene chloride and methanol (95:5 by volume)
7. customwith a mixture (2 liters) of methylene chloride and methanol (90:10 by volume) and collecting 75-cc fractions
8. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C
9. stirringwith stirring with isopropyl ether (40 cc) for 1 hour at a temperature in the region of 20° C.
10. washwashed with isopropyl ether (2×5 cc)
11. customdried under reduced pressure (5 mm Hg; 0.7 kPa) at 40° C