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Oxo-(2-phenyl-5,6,7,8-tetrahydro-indolizin-3-yl)-acetyl chloride (prepared as described in Reference Example 21, 40 g, 0.14 mol) was added portion-wise to a solution of 4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenylamine (prepared as described in Reference Example 94, 18 g, 63.8 mmol) in pyridine (150 mL). The reaction mass was stirred for 1 hour then quenched slowly into cold water (3 L). The precipitated solid was filtered and washed with water (3×50 mL). The solid was dissolved in chloroform (200 mL) and washed successively with bicarbonate solution (3×200 mL) and brine (200 mL). The chloroform layer was separated, diluted with chloroform (800 mL), and to this was added neutral alumina (150 g) and charcoal (5 g). The mixture was stirred for 2 hours at room temperature then filtered through celite. The treatment was repeated with another 75 g of neutral alumina with over night stirring. Filtration and concentration gave a solid which was dissolved in toluene (500 mL) and extracted with 25% aqueous acetic acid solution (3×500 mL). The combined aqueous layers were basified with 25% ammonium hydroxide solution (2 L) to pH ˜7 and extracted with diethyl ether (2×300 mL). The combined ether extracts were washed with bicarbonate solution (2×200 mL), brine (200 mL), dried over sodium sulfate and concentrated in vacuo to give a solid. This was further purified by passing through a short silica pad (60-120 silica gel) eluting with 30% ethyl acetate in chloroform. After concentration, the solid was dissolved at reflux in ethanol (300 mL). The solution was cooled to 0° C., and stirred for 15 minutes, whereupon the precipitated solid was filtered and dried on the sinter. Further drying at 60° C. under high vacuum afforded the title compound N-{4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenyl}-2-oxo-2-(2-phenyl-5,6,7,8-tetrahydro-indolizin-3-yl)-acetamide (10.4 g, 30.5%) as a yellow powder.

1. customthen quenched slowly into cold water (3 L)
2. filtrationThe precipitated solid was filtered
3. washwashed with water (3×50 mL)
4. dissolutionThe solid was dissolved in chloroform (200 mL)
5. washwashed successively with bicarbonate solution (3×200 mL) and brine (200 mL)
6. customThe chloroform layer was separated
7. additiondiluted with chloroform (800 mL)
8. additionto this was added neutral alumina (150 g) and charcoal (5 g)
9. stirringThe mixture was stirred for 2 hours at room temperature
10. filtrationthen filtered through celite
11. stirringstirring
12. filtrationFiltration and concentration
13. customgave a solid which
14. extractionextracted with 25% aqueous acetic acid solution (3×500 mL)
15. extractionextracted with diethyl ether (2×300 mL)
16. washThe combined ether extracts were washed with bicarbonate solution (2×200 mL), brine (200 mL)
17. dry with materialdried over sodium sulfate
18. concentrationconcentrated in vacuo
19. customto give a solid
20. customThis was further purified
21. washeluting with 30% ethyl acetate in chloroform
22. concentrationAfter concentration
23. dissolutionthe solid was dissolved
24. temperatureat reflux in ethanol (300 mL)
25. stirringstirred for 15 minutes, whereupon the precipitated solid
26. filtrationwas filtered
27. customdried on the sinter
28. customFurther drying at 60° C. under high vacuum