SU732263A1 - Method of preparing dibenzo-/b,e/ /1,4/-diazepine drivatives - Google Patents

Description

Dine, as well as the use of derivatives of N- (o-aminophenyl) anthranilic acid having an alkyl substituent on diphenylamine nitrogen, or the introduction of an additional alkyl-ooC position in the 5-position of the dibenzo-b, e 1,4-diazepine ring, if R is hydrogen .

The aim of the invention is to simplify the process and expand the range of target products.

The goal is achieved by treating N- (o-aminophenyl) -anthranilic acid derivatives unsubstituted in diphenylamine nitrogen of formula (III), where R has the above values, Ry is the lower alkoxy group or residue, where R, jH R have the above values, alkyl ester of polyphosphoric acid, the alkyl residue of which contains 1-3 carbon atoms, preferably 10-fold excess of the latter relative to the weight of the compounds of formula (III) in heme:

Moreover, if Rg is an alkoxy group, 5-alkyl-11-oxodibenzo-b ,, 4-diazepines of the formula (Yes, -N .-- are formed).

. n, 1 are obtained

Does Rr residue

VK

5-alkyl-11-aminodibenzo-b, e) 1,4-diazepines of formula (II), the alkyl residue in position 5 of the dibenzo-b, e 1,4-diazepine ring is equivalent to the alkyl residue of the alkyl ester of polyphosphoric acid.

The process proceeds satisfactorily at 100-140s. Target products are recovered by conventional methods. Their structure was confirmed by IR spectroscopy, a comparison of the constants of the compounds obtained with literary data (for known substances), as well as elemental analysis data.

Example 1. 5-Methyl-11-piperidino-5H-dibenzo-b, 4-di-epin.

To 16 g of polyphosphoric acid methyl ester (prepared by dissolving 10.8 g of phosphoric anhydride in 6.5 ml of methyl alcohol) was added 1.6 g of N- (o-aminophenyl) anthranilic acid piperidine. The mixture ia. Is heated in an oil bath at 130–140 ° C for 3.5–4, oh. The end of the reaction is determined using a thin layer | chromatography (TLC) on the plates:. .Silufol UV-254 by the disappearance of the mass of the starting amide (system chloroform: methanol: 3% alachiak, 5). At the end of the exposure, the mass is cooled to 5-10 ° C, 30 ml of cold water is added, and then neutralized with diluted ammonia to pH 8 at a rate So that the temperature in the mass does not exceed. The precipitate which has separated out is filtered and washed with water and neutral reaction.

Obtain 1.3 g (83.5% of the original amide) of the desired product, so pl. 147155С. After recrystallization from methanol, a light yellow substance is obtained with a mp. 159-1 ° C. Literary data: so pl. 157 ° C, 158-159 ° C (acetone-petroleum ether).

Example 2. 5-Methyl-8-chloro-11- (4-methylpiperazino) -5H-dibenzo-4, diazepine.

With stirring, 1.6 g of 4-methylpiperazide N-2- (2-amino-4-chlorophenyl) anthranilic acid are added with stirring to 18 g of polyphosphoric acid methyl ester at 110-115 ° C. The temperature is raised to 130 ° C and stirred at this temperature for 2-2.5 hours. The end of the reaction is determined by thin layer chromatography. The product is isolated as in Example 1. 1.3 g of a greenish-gray cyclic product are obtained (82.3% based on the starting amide), mp. 168-1b9s (from). Literary data: so pl. 163-165 C, 164-165 with (acetone-petroleum ether).

Example 3. 5-Ethyl-11- (4-methylpiperazino) -5H-dibenzo-b ,, 4 diazepine.

1.5 g of N- (aminophenyl) anthranilic acid 4-methylpiperazide are powdered to 15 g of polyphosphoric acid ethyl ester (prepared from 9 g of phosphoric anhydride and 11 ml of absolute ethyl alcohol) and the mixture is kept at 140 s until the starting product disappears in the reaction mass ( TLC on Silufol UV-254 plates) for 2-2.5 h.

The product is isolated in the same way as in Example 1. 1.55 g (quant., Gene yield) of the desired product is obtained, m.p. 171-172 seconds (from methanol). Found,%: with 75.48; H 7.76; N 17.48.

20 24%

Calculated,%; C, 74.96; H 7.55; N 17.48.

Example 4. 5-Methyl-8-chloro-11-oxo-5n-di6benzo, 4-diaaepine.

Analogously to Example 1 of 2 g of N- (2-amino-4-chlorophenyl) -anthranilic acid methyl ester and 20 g of polyphosphoric acid methyl ester (heating for 4 h control on those on Silufol UV-254 plates in the benzene system : methanol 6: 1) 1.67 g (89.3% of the starting amide) of the desired product, m.p. 212-214С (from ethyl alcohol). Literary data: so pl. 214-215 ° C.

Claims (2)

Invention Formula -2 Method for preparing dibenzo- (b, e. 1, 4-diazepines derivatives of general formula (1) or (II) R Where  C-C-alkyl; R. and R, - hydrogen or halogen, the same or different; R and R, lower alkyls or, together with the nitrogen atom to which they are attached, form a heterocycle, which may include a second nitrogen atom, possibly substituted by lower alkyl, Owing to the fact that, in order to simplify the process and expand the range of target products, N- (o-aminophenyl) anthranilic acid derivatives of the general formula five "6 I  . -Rj (#J 0 where R. R is as defined above; RS is a lower alkoxy group or a -N: residue, where R and R. have an index of 5 to 4 The above values are treated with alkyl alkyl ester of polyphosphoric acid, the alkyl residue of which contains 1-3 carbon atoms, at 100- 140C. 0 2. The method according to p. 1, different This is because they use a 10-fold excess of polyphosphoric acid alkyl ester relative to the weight of the compounds of formula (III). five Sources of information taken into account in the examination 1. Swiss patent 416633, cl. 12 p 4/01, publ. 1967 (prototype).