Triethylamine → 1192720-23-2

Temperature

47.5 °C

A solution of (1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-oxo-acetyl chloride (46 g, 0.176 mol) in dry dichloromethane (300 mL) was added to a solution of 4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenylamine (40 g, 0.140 mol) and triethylamine (14.2 g, 0.140 mol) in dry dichloromethane (300 mL) over 15 min. After stirring for 1 h the reaction mixture was quenched into water (200 mL) and the organic phase separated. The aqueous layer was extracted with dichloromethane (2×50 mL) and the combined organic layers were washed successively with water (2×200 mL), brine (2×100 mL), dried over anhydrous sodium sulfate and concentrated to give a solid. This was dissolved in acetone (580 mL) and silica gel was added (72.5 g, 100-200 mesh). The mixture was stirred at room temperature for 1 h, filtered and the solids washed with acetone (75 mL). The silica treatment was repeated a second time. The filtrate was concentrated to ˜300 mL (˜4 vols), activated carbon (8 g) was added and heated at reflux for 15 min. The mixture was cooled to 45-50° C. and filtered over celite, washing with acetone (75 mL). The solution was again concentrated to ˜300 mL and petroleum ether (725 mL, 10 vols) was added, slowly, at reflux. The resulting suspension was cooled to room temperature, stirred for 15 min, then cooled to 0° C. and stirred for 1 h. The solid was filtered off, washed with petroleum ether (150 mL) and dried under vacuum to afford 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-{4-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-phenyl}-2-oxo-acetamide (53.5 g, 74%) as a yellow solid.

1. customwas quenched into water (200 mL)
2. customthe organic phase separated
3. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
4. washthe combined organic layers were washed successively with water (2×200 mL), brine (2×100 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated
7. customto give a solid
8. additionsilica gel was added (72.5 g, 100-200 mesh)
9. stirringThe mixture was stirred at room temperature for 1 h
10. filtrationfiltered
11. washthe solids washed with acetone (75 mL)
12. concentrationThe filtrate was concentrated to ˜300 mL (˜4 vols), activated carbon (8 g)
13. additionwas added
14. temperatureheated
15. temperatureat reflux for 15 min
16. filtrationfiltered over celite
17. washwashing with acetone (75 mL)
18. concentrationThe solution was again concentrated to ˜300 mL and petroleum ether (725 mL, 10 vols)
19. additionwas added
20. temperatureslowly, at reflux
21. temperatureThe resulting suspension was cooled to room temperature
22. stirringstirred for 15 min
23. temperaturecooled to 0° C.
24. stirringstirred for 1 h
25. filtrationThe solid was filtered off
26. washwashed with petroleum ether (150 mL)
27. customdried under vacuum

ORD record

ord-1dcdd63af92c4ecb8bec5ebf7242aade

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993574B2