CS201558B1 - Method of preparing 1-/5-oxohexyl/-3,7-dimethylxanthine - Google Patents

Description

CZECHOSLOVAK SOCIALISTIC DESCRIPTION OF THE INVENTION FOR COPYRIGHT CERTIFICATE 201558 (11) '(Bl) (51) Int. Cl3 C 07 D 473/10 REPUBL 1 (19) XZX KA (22) Entries 14 05 79 (21) (PV 3278—79) (40) Published 29 02 80 OFFICE FOR INVENTIONS AND DISCOVERIES (45) Released 31 03 82 ' 1

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Author of the invention KOVÁŘ PAVOL ing., RYBÁR ALFONZ ing. CSc., BRATISLAVA,

JENDRICHOVSKY JAN ing., HLOHOVEC, ROMANOVA EVA ingKRALIK PETER doc. CSc., BRATISLAVA (54) Preparation of 1- (5-oxohexyl) -3,7-dimethylxanthine

The present invention relates to a process for the preparation of 1- (5-oxo-hexyl) -3,7-dimethylxanthine of the formula I XAA 0 ch5 which is used as an effective peripheral vasodilator.

To date, this compound has been prepared either by reaction of the sodium salt of theobromine and 6-bromo-hexanone-2 in an aqueous alcohol at elevated temperature (in about 26% yield for reacted theobromine), or by reaction with 1 - 3-bromopropyl / theobromine with sodium acetoacetate salt in absolute methanol followed by ketone cleavage (in about 70% yield). (Mohler W., Reiert M., Popendiker K., Ger. Pat. 1,235,320 / 5 Sep. 1964); Mohler W., Reiser M., K. Popendierk, and von Schuh H.-G. U.S. Pat. No. 3,422,107 (Jan. 14, 1969)), or by reaction of potassium] soliteobromine with 6-bromohexanone-2 in a polar aprotic solvent (Czechoslovak Patent No. 164 643; .

The present invention is based on the fact that the alkaline salt of theobromine is not reacted with 6-bromoanone-2 in the presence of alkaline iodide (0.01 to 0.1 M iodide per 1 M alkylating agent) at elevated temperature 40 to 150 ° C in a polar aprotic solvent (dimethylformamide), dimethylacetamide, dimethylsulfoxide, sulfolane) without protonation of the alkali salt of theobromine to theobromine.

The method of the present invention makes it possible to prepare said compound of better purity and, in particular, less time with high yield than previously described. This makes it possible to make better use of the reaction components, especially the expensive 6-bromohexanone-2. In the following, the invention is illustrated by the following examples without limiting the invention to these. Example 1

A mixture of 179 g (1 mol) of 6-bromohexanone-2.175 g (0.8 mol) of theobromine potassium salt and 15 g (0.1 mol) of sodium iodide in 500 ml of Ν-dimethylformamide was heated at 80 ° C with stirring. The reaction mixture was concentrated in vacuo to a syrup to which was added 500 mL of chloroform. The salts were filtered off and the filtrate was concentrated to 1/3 of the pore volume. Adding the meter, respectively. hexane or heptane precipitates 205 g (i.e. 92% of theory) of the product 201558

Claims (1)

2 with a melting point of 99-101 ° C. Crystallization from 2-propanol yields 187 g (i.e., 84% of theory) of 1- (5-oxo-hexyl) -3,7-dimethylxanthine, m.p. 102-103 ° C. EXAMPLE 2 The reaction is carried out in a manner analogous to the previous example, but with different product isolation. The cooled reaction mixture was poured with stirring at 800 g (stirred until the ice was dissolved). The undissolved fractions were filtered off and the filtrate was prepared by the reaction of the alkaline salt of theobromine with 6-bromohexanone-2 in a polar aprotic solvent and extracted with 5x500. ml of benzene. The benzene solution was passed through a silica gel pad and concentrated to dryness. The residue was dissolved in 150 ml of chloroform, dried over sodium sulphate and, after filtration of the drying agent, the product was precipitated by the addition of petroleum ether. 196 g (i.e. 88% of theory) of the product having a melting point of 100 to 102 ° C are obtained. Crystallization from 2-propanol afforded 164 g (i.e. 74% of theory) of 1- (5-oxohexyl) -3,7-dimethylxanthine, m.p. 102-103 ° C. EMBODIMED by the fact that the reaction is carried out in the presence of an alkali iodide at temperatures of 40 to 150 ° C. Jihočeské tiskárny, n. P., Operation 6 Jtndř. HradecPrice: 2.40 Kčs