反应详情

A solution of 2-(2-cyano-10-phenothiazinyl)-1-propyl methanesulphonate, L series (44 g) and 2,5-dihydropyrrol (42.2 g) in anhydrous toluene (250 cc) is heated to 90° C. with stirring for 18 hours. After cooling, the reaction mixture is extracted with distilled water (2×100 cc) and then with N aqueous hydrochloric acid solution (250 cc). The combined acidic aqueous phases are alkalinized with aqueous N sodium hydroxide solution and extracted with ethyl acetate (3×100 cc). The organic phases are combined, washed successively with distilled water (100 cc) and then with saturated aqueous sodium chloride solution (100 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The yellowish oily residue (30.4 g) is purified by chromatography on a column (height: 38 cm; diameter 3.8 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting with a mixture (75:25 by volume) (15 liters) of cyclohexane and ethyl acetate and collecting 1-liter fractions. Fractions 6 to 11 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. to give 10-[1-(2,5-dihydro-1-pyrrolyl)-2-propyl]-2-phenothiazinecarbonitrile, L series (11.15 g) in the form of a yellow oil.

1. temperatureAfter cooling
2. extractionthe reaction mixture is extracted with distilled water (2×100 cc)
3. extractionextracted with ethyl acetate (3×100 cc)
4. washwashed successively with distilled water (100 cc)
5. dry with materialwith saturated aqueous sodium chloride solution (100 cc), dried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C
8. customThe yellowish oily residue (30.4 g) is purified by chromatography on a column (height: 38 cm; diameter 3.8 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa)
9. washeluting with a mixture (75:25 by volume) (15 liters) of cyclohexane and ethyl acetate
10. customcollecting 1-liter fractions
11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C.