反应详情

温度

100 °C

A mixture of 10-[(2RS)-1-(N-ethyl-N-methylamino)-2-propyl]-2-phenothiazinecarbothioamide (2.1 g) and butylamine (8.5 cc) in absolute ethanol (30 cc) is saturated with hydrogen sulphide and heated for 16 hours to a temperature in the region of 100° C. After cooling, the orange solution obtained is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual brown oil is purified by chromatography on a column (height: 4 cm; diameter: 3 cm) of silica gel (0.2-0.063 mm), eluting successively with methylene chloride (2 liters) and with a mixture (90:10 by volume) (1 liter) of methylene chloride and methanol and collecting 60-cc fractions. Fractions 36 to 39 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual orange oil (1.8 g) is again purified by chromatography on a column (height: 25 cm; diameter: 4 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting with mixture (75:25 by volume) (1 liter) of ethyl acetate and cyclohexane and collecting 60-cc fractions. Fractions 5 to 12 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. N-Butyl-10-[(2RS)-1-(N-ethyl-N-methylamino)-2-propyl]-2-phenothiazinecarbothioamide (1.25 g) is thereby obtained in the form of a yellow oil. This product is dissolved in isopropyl ether (100 cc) and treated, dropwise and with stirring, with a 0.28N solution (10.9 cc) of hydrochloric acid in isopropyl ether. After 1 hour's stirring at a temperature in the region of 5° C, the precipitate formed is drained, washed with isopropyl ether (3×10 cc) and dried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C. N-Butyl-10-[(2RS)-1-(N-methyl-N-ethylamino)-2-propyl]-2-phenothiazinecarbothioamide hydrochloride (1.1 g) is thereby obtained in the form of a yellow solid, m.p. 102° C. (melts forming a paste).

1. temperatureAfter cooling
2. customthe orange solution obtained
3. concentrationis concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
4. customThe residual brown oil is purified by chromatography on a column (height: 4 cm; diameter: 3 cm) of silica gel (0.2-0.063 mm)
5. washeluting successively with methylene chloride (2 liters) and with a mixture (90:10 by volume) (1 liter) of methylene chloride and methanol
6. customcollecting 60-cc fractions
7. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
8. customThe residual orange oil (1.8 g) is again purified by chromatography on a column (height: 25 cm; diameter: 4 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa)
9. washeluting with mixture (75:25 by volume) (1 liter) of ethyl acetate and cyclohexane
10. customcollecting 60-cc fractions
11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C