BIS(2-BROMOETHYL)AMINE HYDROBROMIDE

Uses

2,2''-Dibromodiethylamine Hydrobromide is used in the synthesis of quinone phosphorodiamidate drugs that target DT-diaphorase, an enzyme that is overexpressed in solid tumors. Also used in the preparation of anti-depressive drugs, in the treatment of major depressive disorders. Trazadone Impurity.

Uses

Bis(2-bromoethyl)amine hydrobromide is used in the synthesis of quinone phosphorodiamidate drugs that target DT-diaphorase, an enzyme that is overexpressed in solid tumors. Also used in the preparat ion of anti-depressive drugs, in the treatment of major depressive disorders. Trazadone Impurity.

Synthesis

The general procedure for the synthesis of bis(2-bromoethyl)amine hydrobromide from diethanolamine is as follows: 157.5 g (1.5 mol) of diethanolamine is added to a 2-liter three-necked flask equipped with a refluxing or distillation apparatus. 1.35 liters of 48% hydrobromic acid is slowly added with stirring (note: this process is exothermic). The reaction mixture was heated in an oil bath at 180-200°C with a controlled vapor temperature of 122°C until 350 ml of liquid was distilled. Subsequently, the unit was adjusted to reflux and kept for 1 hour. The distillation process was repeated and 465 ml of distillate was collected. The unit was again adjusted to reflux and maintained for 3.75 hours before 400 ml of liquid was distilled. After completion of the reaction, the mixture was cooled and 300 ml of ethyl acetate was added to the residue. The resulting suspension was stirred in an ice bath for 1 hour. The precipitate was collected by filtration and washed with ethyl acetate. A final 367 g of white crystalline product was obtained in 78.5% yield with a melting point of 130-135°C.

References

[1] Patent: US2004/266802, 2004, A1. Location in patent: Page 7-8
[2] Patent: US5233031, 1993, A
[3] Journal of Medicinal Chemistry, 2000, vol. 43, # 16, p. 3157 - 3167
[4] Patent: US2007/259883, 2007, A1. Location in patent: Page/Page column 6; 9