1-(Piperazin-1-yl)propan-1-one → HCID 20542234, compound

Temperature

2 °C

A solution of 1-propionylpiperazine (6.8 g) in anhydrous acetonitrile (50 cc) is added, at 20° C., to a suspension of 7-(5-chloropyrid-2-yl)-3-methoxy-8-oxo-6-phenoxycarbonyloxy-3,4,7,8-tetrahydro-2H,6H-1,4-dithiepino[2,3-c]pyrrole (11.15 g) in anhydrous acetonitrile (80 cc). The reaction mixture is heated under reflux for 6 hours. The acetonitrile is evaporated off under reduced pressure (20 mm Hg; 2.67 kPa). The residue is treated with water (100 cc) and extraction is carried out three times with methylene chloride (total 210 cc); the organic extracts are washed twice with distilled water (total 200 cc), dried over anhydrous sodium sulphate and evaporated to dryness. The resulting residue (14.7 g; oily) is dissolved in a mixture of chloroform and methanol (97:3 by volume; 50 cc). The solution is chromatographed on silica (0.04-0.063 mm; 400 g) contained in a column of diameter 6 cm, under a pressure of 140 kPa. Elution is carried out with the solvent mixture mentioned above under a pressure of 140 kPa. 1800 cc of eluate are collected and discarded, and then 600 cc of eluate are collected and evaporated to dryness under reduced pressure (20 mm Hg; 2.67 kPa). The resulting partially crystalline residue (11.0 g) is dissolved in a boiling mixture of acetonitrile (10 cc) and diisopropyl ether (50 cc). After cooling the solution for 2 hours at 2° C., the resulting crystals are filtered off, washed twice with diisopropyl ether (total 20 cc) and dried under reduced pressure (20 mm Hg; 2.67 kPa) at 20° C. The resulting product (4.1 g; m.p. 160° C.) is dissolved in boiling acetonitrile (60 cc). After cooling the solution for 2 hours at 2° C., the resulting crystals are filtered off, washed twice with diisopropyl ether (total 80 cc) and dried under reduced pressure (0.2 mm Hg; 0.026 kPa) at 50° C. 7-(5-Chloropyrid-2-yl)-3-methoxy-8-oxo-6-(4-propionylpiperazin-1-yl)carbonyloxy-3,4,7,8-tetrahydro-2H,6H-1,4-dithiepino[2,3-c]pyrrole (1.2 g), melting at 226° C., is obtained.

1. temperatureThe reaction mixture is heated
2. temperatureunder reflux for 6 hours
3. customThe acetonitrile is evaporated off under reduced pressure (20 mm Hg; 2.67 kPa)
4. additionThe residue is treated with water (100 cc) and extraction
5. washthe organic extracts are washed twice with distilled water (total 200 cc)
6. dry with materialdried over anhydrous sodium sulphate
7. customevaporated to dryness
8. dissolutionThe resulting residue (14.7 g; oily) is dissolved in a mixture of chloroform and methanol (97:3 by volume; 50 cc)
9. customThe solution is chromatographed on silica (0.04-0.063 mm; 400 g)
10. washElution
11. custom1800 cc of eluate are collected
12. custom600 cc of eluate are collected
13. customevaporated to dryness under reduced pressure (20 mm Hg; 2.67 kPa)
14. dissolutionThe resulting partially crystalline residue (11.0 g) is dissolved in a boiling mixture of acetonitrile (10 cc) and diisopropyl ether (50 cc)
15. filtrationthe resulting crystals are filtered off
16. washwashed twice with diisopropyl ether (total 20 cc)
17. customdried under reduced pressure (20 mm Hg; 2.67 kPa) at 20° C
18. dissolutionThe resulting product (4.1 g; m.p. 160° C.) is dissolved
19. temperatureAfter cooling the solution for 2 hours at 2° C.
20. filtrationthe resulting crystals are filtered off
21. washwashed twice with diisopropyl ether (total 80 cc)
22. customdried under reduced pressure (0.2 mm Hg; 0.026 kPa) at 50° C

ORD record

ord-d803412d2ab245da93fc6f7e39fe7838

Source dataset

uspto-grants-1982_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04327095