Process for removing trace solvent from a material

#The invention relates to a factory scale process for removing trace solvent from a material, especially a hygroscopic material. In particular, the invention relates to an improved process for producing suramin, the hexasodium salt of a polysulfonated naphthylurea, 8,8′-[carbonylbis[imino-3,1-phenylene-carbonylimino (4-methyl-3,1 -phenylene) carbonyl-imino]]bis-1,3,5-naphthalenetrisulfonic acid.

#Suramin has been utilized clinically since the 1920s as an antiparasitic agent, and more recently has been shown to be active in the treatment of metastatic cancer; Stein et al., J. Clin. Oncology 1989;7(4):499-508. U.S. Pat. Nos. 5,767,110 and 5,597,830 describe the synergistic effect of suramin in combination with a vinca alkaloid or estramustine for treating cancer.

#In addition, suramin can be used for treating autoimmune and allergic diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, glomerular nephrites, systemic lupus erythematosus, polymyositis, Sjogren's syndrome, asthma, and other inflammatory alveolar diseases. Suramin can also be used for treating AIDS and human T cell leukaemia virus.

#142 kg 8-[3-(3-Aminobenzamido)-4-methylbenzamido]-1,3,5-napthalenetrisulfonic acid sodium salt prepared by known methods and 1150 liters water are charged to a reaction vessel and agitated for approximately 10 minutes until the solution is dissolved. 2 N hydrochloric acid (71 kg concentrated hydrochloric acid in 284 liters water) is charged to the reaction vessel until the pH is in the range 3.8 to 4.0.

#A solution of 17 kg triphosgene and 62 kg toluene are charged to the reaction vessel over approximately 2 hours. The pH is maintained at 3.5 to 4.0 by charging as required with a solution of 2 N sodium hydroxide (21.3 kg sodium hydroxide in 264 kg water) and the temperature maintained at 20° C. to 3° C. After agitation for at least 1 hour, 206 kg toluene is added to the reaction vessel and the contents agitated at 70 rpm for 15 minutes. The contents are allowed to settle and the lower rich aqueous layer is transferred to another vessel. A number of toluene washes of the rich aqueous layer are carried out to remove residual phosgene, and all the waste toluene streams are combined for decontamination before disposal. The pH of the rich aqueous layer is adjusted to 6.0 to 6.5 with 2 N sodium hydroxide and the contents agitated for 15 minutes. A full vacuum is applied to the vessel and the contents distilled at 60° C. until 234 to 248 liters remain. The pH is adjusted to 6.0 to 6.5 using 2 N sodium hydroxide. The contents are then heated to 60° C. to 70° C. and 1005 kg filtered methanol is added. The contents are polish filtered through a single plate, a multiplate sparkler, and multielement cartridge filter.

#After filtration, the filtrate is cooled to 34° C. to 36° C. and agitated at 50 to 90 rpm and further cooled at about 1° C./10 minutes until crystallization commences. While cooling, the contents are seeded with 10 g aliquots of suramin seeds. When crystallization begins the contents are agitated for 8 hours without temperature regulation. After 8 hours the contents are agitated at 15° C. to 20° C. for at least 6 hours, the contents are further cooled to −2 to +2° C. and agitated for at least 3 hours. The crude suramin product is centrifuged and discharged to polyethylene lined bins.