Diethylcarbamazine
From The Cure For The Needy
Contents |
Diethylcarbamazine (Hetrazan)
Effective against
Diethylcarbamazine is an anthelmintic drug (a drug that expels parasitic worms (helminths) from the body by either stunning or killing them).
Cost
From Sigma-Aldrich: 80.60 USD (25g)
Reported Routes of Synthesis
Condensation of methylamine (I) with ethylene oxide (II) provides aminodiol (III), which is converted to the corresponding dichloride (IV) upon treatment with SOCl2. Subsequent cyclization of dichloride (IV) with ammonia leads to N-methylpiperazine (V), which is either acylated with phosgene (VIa) or with ethyl chloroformate (VIb) producing carbamoyl chloride (VIIa) or carbamate (VIIb), respectively. Finally, condensation of intermediates (VIIa) or (VIIb) with diethylamine (VIII) yields the title compound (1). Alternatively, the title compound can be obtained by the following ways: 1) By condensation of piperazine hexahydrate (IX) with N,N-diethylcarbamoyl chloride (X) in EtOH at 45-50°C, followed by Eschweiler-Clarke reaction of the resulting 1-diethylcarbamylpiperazine (XI) with formaldehyde and formic acid (2). 2) By condensation of N,N-diethylcarbamoyl chloride (X) with 1-methylpiperazine (V) in CHCl3 or its dihydrochloride salt hydrate (XII) in the presence of NaOH in H2O at 35-40°C (2).
Kushner, S.; Brancone, L.M. Experimental chemotherapy of filariasis; the preparation of derivatives of piperazine J Org Chem, 1948, 13(1): 144
Cost of Starting Materials and Selected Reagents:
Methylamine solution (2.0 M in methanol) from Sigma-Aldrich: 96.6 USD (100 mL)
Ethylene oxide from Sigma-Aldrich: 498.5 USD (227 g)
Thionyl chloride from Sigma Aldrich: 64.4 USD (500 mL)
Ammonia solution (2 M in methanol) from Sigma-Aldrich: 57.8 USD (100 mL)
Ethyl chloroacetate pricing not available from Sigma-Aldrich
Diethylamine from Sigma-Aldrich: 39.8 USD (250 mL)
Please reference Vardnayan, R and Hruby, V. Synthesis of Essential Drugs. Elsevier:2006. pg. 586 for a short synthesis.
Cost of Starting Materials and Selected Reagents:
1-Methylpiperazine from Sigma-Aldrich: 19.9 USD (5 g)
Diethylcarbamoyl chloride from Sigma-Aldrich: 34.5 (100 mL)