反应详情

温度

60 °C

A mixture of a 33% strength solution (10 cc) of methylamine in absolute ethanol and 10-[(2RS)-1-diethylamino-2-propyl]-2-phenothiazinecarbothioamide (2 g) in absolute ethanol (15 cc) is brought for 24 hours to a temperature in the region of 100° C. After cooling, the mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residue is taken up with ethyl acetate (100° C.), washed with distilled water (2×50 cc), dried over magnesium sulphate in the presence of charcoal 3S, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual orange oil (1.7 g) is purified by chromatography on a column (height: 25 cm; diameter: 2.5 cm) of silica gel (0.04-0.063 mm) with a slight excess pressure of nitrogen (40 kPa), eluting successively with ethyl acetate (750 cc) and with a mixture (90:10 by volume) (500 cc) cf ethyl acetate and ethanol and collecting 50-cc fractions. Fractions 2 to 7 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual brown oil (1.3 g) is dissolved at 50° C. in ethanol (3 cc) and the solution obtained is poured into a solution of fumaric acid (0.39 g) in ethanol (3 cc), with stirring and at a temperature in the region of 60° C. After 1 hour with stirring at a temperature in the region of 5° C., the solid formed is drained, washed with ethanol (3×1 cc) and dried in the air. This solid is redissolved in ethanol (20 cc) under reflux and then stored for 1 hour at a temperature in the region of 5° C. The solid formed is drained, washed with ethanol (3×1 cc) and dried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C. 10-[(2RS)-1-diethylamino-2-propyl]-N-methyl-2-phenothiazinecarbothioamide acid fumarate (1.15 g) is thereby obtained in the form of a yellow solid, m.p. 224° C.;

1. temperatureAfter cooling
2. concentrationthe mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
3. customis taken up with ethyl acetate (100° C.)
4. washwashed with distilled water (2×50 cc)
5. dry with materialdried over magnesium sulphate in the presence of charcoal 3S
6. filtrationfiltered
7. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
8. customThe residual orange oil (1.7 g) is purified by chromatography on a column (height: 25 cm; diameter: 2.5 cm) of silica gel (0.04-0.063 mm) with a slight excess pressure of nitrogen (40 kPa)
9. washeluting successively with ethyl acetate (750 cc) and with a mixture (90:10 by volume) (500 cc) cf ethyl acetate and ethanol
10. customcollecting 50-cc fractions
11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
12. dissolutionThe residual brown oil (1.3 g) is dissolved at 50° C. in ethanol (3 cc)
13. customthe solution obtained
14. stirringAfter 1 hour with stirring at a temperature in the region of 5° C.
15. customthe solid formed
16. washwashed with ethanol (3×1 cc)
17. customdried in the air
18. dissolutionThis solid is redissolved in ethanol (20 cc)
19. temperatureunder reflux
20. waitstored for 1 hour at a temperature in the region of 5° C
21. customThe solid formed
22. washwashed with ethanol (3×1 cc)
23. customdried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C