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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence