反应详情

温度

65 °C

7-Chloroformyl-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole hydrochloride (24 g) is added, at a temperature in the vicinity of 65° C., to a solution of 3-aminobenzophenone (15.7 g) and triethylamine (16.1 g) in dioxane (400 cc) which is heated to a temperature in the vicinity of 65° C., in the course of 15 minutes. The suspension obtained is heated, with stirring, at a temperature in the vicinity of 100° C. for 6 hours and then stirred at a temperature in the vicinity of 20° C. for 16 hours. The solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C. The residue is dissolved in methylene chloride (500 cc) and the solution obtained is washed twice with distilled water (200 cc in total), 4 times with an aqueous 1N sodium hydroxide solution (800 cc in total) and 5 times with distilled water (500 cc in total) and then dried over anhydrous magnesium sulphate, treated with decolourizing charcoal (0.5 g), filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C. The product obtained is chromatographed on an 8.5 cm diameter column containing silica (0.02-0.045 mm; 1 kg). Elution is carried out with mixtures of cyclohexane and ethyl acetate at a pressure of 0.4 bar (40 kPa), collecting 500 cc fractions. The first 10 fractions originating from elution with an ethyl acetate:cyclohexane (60:40 by volume) mixture and the following 5 fractions originating from elution with an ethyl acetate:cyclohexane (80:20 by volume) mixture are discarded. The following 10 fractions originating from elution with an ethyl acetate:cyclohexane (80:20 by volume) mixture and the following 2 fractions originating from elution with an ethyl acetate:cyclohexane (90:10by volume) mixture are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C. A crude product (26.5 g) is thereby obtained, which is dissolved in boiling acetonitrile (150 cc). Decolourizing charcoal (0.5 g) is added to the solution obtained and the suspension is filtered in the heated state. The filtrate obtained is cooled at a temperature in the vicinity of 45° C. for 16 hours. The crystals formed are separated by filtration, washed 3 times with acetonitrile cooled to a temperature in the vicinity of 4° C. (90 cc in total) and 3 times with diethyl ether (90 cc in total) and then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 20° C. in the presence of potassium hydroxide pellets. N-(3-benzoylphenyl)-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (14 g) in the form of creamcoloured crystals, m.p. 154° C, is thereby obtained.

1. customThe suspension obtained
2. temperatureis heated
3. stirringstirred at a temperature in the vicinity of 20° C. for 16 hours
4. customThe solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 60° C
5. dissolutionThe residue is dissolved in methylene chloride (500 cc)
6. customthe solution obtained
7. washis washed twice with distilled water (200 cc in total), 4 times with an aqueous 1N sodium hydroxide solution (800 cc in total) and 5 times with distilled water (500 cc in total)
8. dry with materialdried over anhydrous magnesium sulphate
9. additiontreated with decolourizing charcoal (0.5 g)
10. filtrationfiltered
11. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C
12. customThe product obtained
13. customis chromatographed on an 8.5 cm diameter column
14. additioncontaining silica (0.02-0.045 mm; 1 kg)
15. washElution
16. customcollecting 500 cc fractions
17. washThe first 10 fractions originating from elution with an ethyl acetate:cyclohexane (60:40 by volume) mixture
18. washthe following 5 fractions originating from elution with an ethyl acetate:cyclohexane (80:20 by volume) mixture
19. washThe following 10 fractions originating from elution with an ethyl acetate:cyclohexane (80:20 by volume) mixture
20. washthe following 2 fractions originating from elution with an ethyl acetate
21. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C
22. customA crude product (26.5 g) is thereby obtained
23. dissolutionwhich is dissolved
24. customobtained
25. filtrationthe suspension is filtered in the heated state
26. customThe filtrate obtained
27. temperatureis cooled at a temperature in the vicinity of 45° C. for 16 hours
28. customThe crystals formed
29. customare separated by filtration
30. washwashed 3 times with acetonitrile
31. temperaturecooled to a temperature in the vicinity of 4° C. (90 cc in total) and 3 times with diethyl ether (90 cc in total)
32. dry with materialdried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 20° C. in the presence of potassium hydroxide pellets