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A simple method for isolating temozolomide, which is used to treat several types of malignant tumors, from its dimethylsulfoxide (DMSO) solvate was investigated. The method consisted of treating temozolomide DMSO solvate with a refluxing Me 2 CO:H 2 O mixture. It was found that decreasing the H 2 O content in the mixture and reducing the reflux time improved the purity of the final product. The best result was obtained by refluxing the sample in anhydrous Me 2 CO. The reproducibility of the proposed method was demonstrated. It was established that the size of temozolomide crystals obtained by this method was much smaller than after recrystallization from aqueous Me 2 CO.Keywords: temozolomide, dimethylsulfoxide solvate.Temozolomide (I, 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide) is an imidazotetrazine heterocyclic compound that possesses antitumor activity and is used to treat malignant gliomas and melanomas and other malignant tumors [1]. Compound I is stable in acidic solution (pH < 5) and labile in basic solution (pH > 7). Therefore, it can be used perorally. Compound I hydrolyzes spontaneously at physiological pH values to give 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide and then fragments to 5-aminoimidazole-4-carboxamide and methyldiazonium cation. The latter is a methylating agent with respect to DNA [2 -4]. A convenient method for synthesizing I is cycloaddition of methylisocyanate to 5(4)-diazoimidazole-4(5)-carboxamide, which in turn is obtained from 5(4)-aminoimidazole-4(5)-carboxamide (Scheme 1) [5 -7]. The reaction is carried out in dimethylsulfoxide (DMSO). The isolated product requires additional purification in order to be used as a drug. Thus, we observed during reproduction of the described method that I was isolated as its DMSO solvate with a I:DMSO mole ratio of 1:1. However, the product without DMSO is used in medical practice.Compound I can be isolated from the solvate by recrystallization from aqueous Me 2 CO. However, large volumes of solvents must be used because of its poor solubility. A method for purifying I by rinsing with aqueous Me 2 CO was also described [6]. This method consisted of several sequential steps of treating the solvate with Me 2 CO, H 2 O, and again with Me 2 CO. A drawback of this method was the number of operations.The goal of the present study was to develop an improved method for isolating I from its DMSO solvate. EXPERIMENTAL PARTThe DMSO solvate of I was prepared by the literature method [8]. 398 0091-150X/14/4806-0398

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The results of proline-catalyzed aldol reaction of acetone with O,O′-alkylidene derivatives of glyceraldehyde are determined by the configuration of the chiral center in the aldehyde. The reaction of (S)-2,3-O-alkylideneglyceraldehyde with acetone in the presence of L-proline was characterized by higher diastereoselectivity.