反应详情

温度

5 °C

A solution of 10-[(2RS)-1-(1-pyrrolidinyl)-2propyl]-2-phenothiazinecarbothioamide (0.9 g) and propylamine (3 cc) in absolute ethanol (18 cc) is saturated with hydrogen sulphide, and the mixture is brought to a temperature in the region of 100° C. for 16 hours. After cooling, the mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. to obtain a yellow oil. This oil 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 methylene chloride (100 cc) and then a mixture (95:5 by volume) (300 cc) of methylene chloride and methanol and collecting 50-cc fractions. Fractions 3 to 5 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual yellow oil (1 g) is dissolved in ethanol (9 cc) under reflux and treated with a boiling solution of fumaric acid (0.29 g) in ethanol (5 cc). The mixture is allowed to cool and is maintained for 4 hours at a temperature in the region of 5° C. The crystals formed are drained, washed with ice-cold ethanol (2 cc) and dried under reduced pressure (5 mm Hg; 0.7 kPa) at 35° C. N-propyl-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide neutral fumarate (1.12 g) is thereby obtained in the form of yellow crystals, m.p. 150°-152° C.

1. temperatureAfter cooling
2. concentrationthe mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C.
3. customto obtain a yellow oil
4. customThis oil 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)
5. washeluting successively with methylene chloride (100 cc)
6. customa mixture (95:5 by volume) (300 cc) of methylene chloride and methanol and collecting 50-cc fractions
7. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
8. dissolutionThe residual yellow oil (1 g) is dissolved in ethanol (9 cc)
9. temperatureunder reflux
10. additiontreated with a boiling solution of fumaric acid (0.29 g) in ethanol (5 cc)
11. temperatureto cool
12. customThe crystals formed
13. washwashed with ice-cold ethanol (2 cc)
14. customdried under reduced pressure (5 mm Hg; 0.7 kPa) at 35° C