反应详情

A mixture of (2RS)-2-(2-cyano-10-phenothiazinyl)-1-propyl methanesulphonate (10 g) and pyrrolidine (11.6 cc) in toluene (50 cc) is brought to 90° C. with stirring for 24 hours. After cooling, the mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. and the residue is taken up with ethyl ether (200 cc) and 4N aqueous sodium hydroxide solution (15 cc). After stirring for 10 minutes, settling is allowed to take place and the organic phase is washed with saturated aqueous sodium chloride solution (3×25 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 20° C. The residual oil (11.3 g) is dissolved in 0.5N aqueous hydrochloric acid solution (60 cc). This solution is washed with ethyl ether (100 cc), then alkalinized with an excess of N aqueous sodium hydroxide solution and extracted with ethyl ether (100 cc). The organic phase is washed with saturated aqueous sodium chloride solution (50 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 20° C. The residual yellow oil (9.5 g) is purified on a column (height: 30 cm; diameter: 5.8 cm) on silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting with a mixture (95:5 by volume) (one litre) of methylene chloride and methanol and collecting 100-cc fractions. Fractions 3 to 10 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. 10-[2RS]-1-(1-Pyrrolidinyl)-2-propyl]-2-phenothiazinecarbonitrile (5.45 g) is thereby obtained in the form of a yellow oil.

1. customis brought to 90° C.
2. temperatureAfter cooling
3. concentrationthe mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C.
4. stirringAfter stirring for 10 minutes
5. washthe organic phase is washed with saturated aqueous sodium chloride solution (3×25 cc)
6. dry with materialdried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 20° C
9. dissolutionThe residual oil (11.3 g) is dissolved in 0.5N aqueous hydrochloric acid solution (60 cc)
10. washThis solution is washed with ethyl ether (100 cc)
11. extractionextracted with ethyl ether (100 cc)
12. washThe organic phase is washed with saturated aqueous sodium chloride solution (50 cc)
13. dry with materialdried over magnesium sulphate
14. filtrationfiltered
15. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 20° C
16. customThe residual yellow oil (9.5 g) is purified on a column (height: 30 cm; diameter: 5.8 cm) on silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa)
17. washeluting with a mixture (95:5 by volume) (one litre) of methylene chloride and methanol
18. customcollecting 100-cc fractions
19. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C