反应详情

温度

115 °C

A stirred suspension of 10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide (2 g) and 2-methylbutylamine (3 cc) in anhydrous ethanol (15 cc) is saturated with hydrogen sulphur and heated for 1 hour to a temperature in the region of 115° C. After cooling, the mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The residual yellow paste is taken up with ethyl acetate (30 cc) and distilled water (20 cc). The organic phase is separated, washed with saturated aqueous sodium chloride solution (20 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual viscous yellow oil (2.2 g) is purified by chromatography on a column (height: 40 cm; diameter: 3.2 cm) of silica gel (0.04-0.063 mm), eluting with a mixture (92:8 by volume) (300 cc) of ethyl acetate and methanol and collecting 25-cc fractions. Fractions 6 to 11 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. N-[(2RS)-2-Methylbutyl]-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide (1.8 g) is thereby obtained in the form of a viscous yellow oil. 0.4 g of this oil is dissolved in isopropyl ether (15 cc), and a 3.3N solution (0.4 cc) of hydrochloric acid in isopropyl ether is added. The precipitate formed is drained, washed with isopropyl ether (3×5 cc) and dried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C. N-[(2RS)-2-Methylbutyl]-10-[(2RS)-1-(1-pyrrolidinyl)-2-propyl]-2-phenothiazinecarbothioamide hydrochloride (0.4 g is thereby obtained in the form of a yellow powder, m.p. 155°-160° C. (melts forming a paste).

1. temperatureAfter cooling
2. concentrationthe mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C
3. distillationdistilled water (20 cc)
4. customThe organic phase is separated
5. washwashed with saturated aqueous sodium chloride solution (20 cc)
6. dry with materialdried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
9. customThe residual viscous yellow oil (2.2 g) is purified by chromatography on a column (height: 40 cm; diameter: 3.2 cm) of silica gel (0.04-0.063 mm)
10. washeluting with a mixture (92:8 by volume) (300 cc) of ethyl acetate and methanol
11. customcollecting 25-cc fractions
12. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C