SU677357A1 - Derivatives of 5,6-dihydrodipyrimido(4,5-b)(5,4-f)-(1,4)thiazepine and method of producing same - Google Patents

Abstract

1, Derivatives of 5,6-dihydrodipyri-mido

Description

This invention relates to derivatives of a new heterocyclic system, namely, 5.6 dihydro-di-pyrimido (4,5-b) - (5,4-f) (1,4) thiazepine of the general formula

(I)

where R is methyl, ethyl or isopropyl, and to give them a spore.

These compounds may be of interest as potential biological actives (compounds or intermediates for the synthesis of the latter. The presence of reactive moieties such as C1-, W-, OA1K, -S- in compounds of the general formula I opens wide possibilities in this regard.

A known method for the preparation of pyrimido derivatives (4,5-b) - (1,5) benzthiazepine of general formula 1a is obtained by reacting the corresponding 5 acyl-6-chorpyrimidine with o-aminothiophenol at 170-190 ° C.

The scheme of the known method. -. n1 -.

pi g

 g

with

to PMNDS Ri

(la)

where R R is methyl or aryl P. In this way, it is not possible to obtain pyramidothiases of general formula I.

The purpose of this invention is chemical / new compounds containing a new combination of lime bond types: dihydro-1,4-: Tydiste: Pine new cycle jointed with two (Ø: pyrymidine rings. -.

The method for preparing the di. H1yyyyado (4,5-b) (5,4-f) - (1,4) thiase / yine derivatives of the general formula I consists in toM that 4 methoxy-5-amino-6-mercaptpyrimidine of the formula

OSSN

ln

(Ii)

Expose to interaction with 4,6-dichlor-5-0ormylpyrimidine and an excess of lower alcohol of the general formula

(Iii)

R-ou

where R is methyl, ethyl or isopropyl, in case of alkali metal hydroxide at 1.8-20 seconds.

As the alkali metal hydroxide, it is advisable to use sodium hydroxide or potassium hydroxide.

In a process for the preparation of compounds of formula I, the formation of thiazepine

rings consists of two etlup. The first stage is the combination of two aromatic knees, suly1) and 1.11M bridge

6; ™ °

N C1 HjCO

The second stage - the interaction of the amino group with the carbonyl-containing substituent (with formyl or acetyl groups), which are in ortho positions to the sulfur atom that binds both aromatic or heterocyclic rings. easily dehydrating. obtaining azomethine fragment.

Compounds of total I - light yellow crystalline solids, soluble in alcohols, insoluble in water, petroleum, sulfuric esters, have a melting point of 136-226 s, stable in air.

The structure of the compounds of general formula I is confirmed by elemental analysis data and their spectral characteristics,

In the IR spectra of the compounds obtained, there are no absorption bands of carbonyl and primary amino groups; there is an absorption band of the secondary amino group (3300 cm). In the mass spectra there are peaks corresponding to the molecular ion: m of the substances obtained.

In the PMR spectra of the dipyrimidothiazepine general formula I, there are two doublets in the range of 5.85-6.08 and 5.35-5.40 m, d. These signals correspond in intensity to one proton and belong to the NH and CH groups in positions 5 and 6 of the dipyrimido molecule (4,5-b) (5,4-f) - (1,4) thiazepine. The interaction of the protons of the N-H- and CI- groups, leading to their mutual separation by. two doublets indicate the cyclic structure of compounds I and the presence in the compounds of the general formula I of the C-N-bond. The following examples illustrate the process for the preparation of compounds of general formula I. Example 1 4,6-Dimethoxy-7 chloro-5, 6-dihydro-di-pyrimido- (4,5-b) (5,4-f) (1,4) thiazepine. . . To a solution of 0.5 g (3.18 mop) of methoxy-5-amino-6-mercaptopyrmidine in 30 ml of methanol; containing 0.2 g of NaOH, add patcrSop 0.6 g (3.39 mml) 4, 6-Dichloro-5-formylpyridine in 10 MP of methanol. The reaction mixture is stirred at 18-20 ° C for 12 hours, filtered and the filtrate is evaporated without heating to 1/3 of the initial volume. The precipitated precipitate is filtered, and 0.6 g (60%) is obtained. 4,6-dimethoxy-7-xdor-5,6-dihydrop rimido (4, 5) (5,4-f) (1,4) thiazepine in light yellow crystalline 1: o powder with m, pl. 226-228s (water Mie Tanol). Found,%: C 42.24; H 3.28; C1 11.28; N 22.60; S 10.33. C H oClHsOzS Calculated,%: C 42.37; H 3.23; C1 11.37; Ы 22.47; S 10.28. Example 2. 4-Methoxy-6-etrxy-7-chloro 5, 6-dihydro-pyrimido (4.5b) (5,4-f) (1,4) thiazepine. . To a solution of 0.5 g (3.18 mmol) of 4-methoxy-5-amino-6-mercaptopyrimidine in 30 ml of ethanol containing 0.2 g of NaOH, a solution of 0.6 g (3.39 mmol) 4 is added. , 6-dichloro-5-formylpyrimidine in 10 ml of ethanol. The reaction mixture is stirred at 18-20 ° C for 12 hours, filtered, the filtrate is evaporated to 1/3 of the initial volume without heating, and the precipitated precipitate is filtered off. 0.6 g (57.5%) of 4-metoxy-6-ethoxy-5,6-dihydroshifimoado (4,5-b) (5,) (1,4) thiazepine is obtained in the form of a light yellow crystalline powder from m.p. 136138 ° C (aqueous ethanol). Found%: C44.28; H 3.73; C1 11.17; N 21.37; S 9.77. Calc; sleno,%: C 44.24; C 3.71; C1 10.87; N 21.49; S 9.84. EXAMPLE 3, 4-Methxi-b-isopropoxy-7-chloro-5, 6-dihydro-di-pyrimido (4,5-b) (5,4-f) (1,4) thiazepine. . To a solution of 0.5 g (3.18 mmol) of 4methoxy-5-amino-6 mercaptopyrimidine in 30 ml of isopropanol containing O, 2 g of NaOH, add a solution of 0.6 g (3.39 mmol) of 4,6-dichloro -5-frrmylp1 rimioin in 10 ml of isopropanol. The reaction mixture is stirred for 12 hours at 18–20 ° C, filtered, the filtrate is evaporated to 1/3 of the original volume without heating. Out of the filter is filtered. 0.40 g (36%) of 4-methoxy-6-isolropic-7-chloro-5, 6-dihydro-di-pyrimido (4,5-b) (5,4-f) (1,4) t "azepine is obtained in the form of light yellow crystalline powder, with so pl. 160-162 ° C (aqueous isopropanol). Found,%: C 45.96; H 4.05; C1 10.81; N 20.23; S 9.21. С, П, 4С1% ОЗЗ Calculated,%: С 45.94; H 4.15 ;; C1 10.43; N 20.60; S 9.43.

Claims (3)

1. Derivatives of 5,6-dihydro-pyrimido (4,5-b) (5,4 - £) - (1,4) thiazepine 2 where K is methyl, ethyl or isopropyl. 2. The method of producing compounds According to claim 1, characterized in that 4-methoxy-5-amino-6-mercaptopyrimidine of the formula is reacted with 4,6-dichloro-5-formyl pyrimidine and an excess of lower alcohol of the general formula K - OH (III) where K has the above values, in the presence of an alkali metal hydroxide at 18-20 ° C. 3. The method according to p. 2, characterized in that sodium hydroxide or potassium is used as the alkali metal hydroxide. 5TS 677357 This invention relates to derivatives of a new heterocyclic system, namely, _x 5,6-dihydrodirimido (4,5-b) - (5,4-£) (1,4) thiazepine of the general formula II 10 where E is methyl, ethyl or isopropyl, and to obtain them. These compounds may be of interest as potential biological active compounds or intermediates for the synthesis of the latter. The presence in compounds of the general formula I of such reactive groups as C1-, ΝΗ-, 0A1K, -5-, open 3 677357 Λ There are ample opportunities in this regard.