HU183330B - Process for producing new of 2,4,8-triazaphenalenium-salts - Google Patents

Abstract

2,4,8-Triazaphenalenium salts are described of the general formula… …<IMAGE>… wherein… R<1> stands for C1-4 alkyl or phenyl,… R<2> stands for C1-4 alkyl or phenyl,… R<3> represents C1-4 alkyl, C7-12 aralkyl or phenyl,… R<4> represents hydrogen, C1-4 alkyl,… C7-12 aralkyl, phenyl (optionally substituted by one or more groups which are the same or different and selected from C1-4 alkyl, C1-4 alkoxy, C1-4dialkylamino, halogen, hydroxy and nitro) or… R<3> and R<4> when taken together form a group of the general formula… …<IMAGE>… wherein R<11> is hydrogen or C1-4 alkoxy,… R<5> stands for hydrogen, C1-4 alkyl, phenyl (optionally substituted by one or more groups which are the same or different and selected from C1-4alkyl, C1-4 alkoxy, C1-4 dialkylamino, halogen, hydroxy and nitro),… with the proviso that when R<4> is hydrogen, R<5> is other than hydrogen,… R<6> stands for hydrogen or C1-4 alkyl,… R<7> stands for hydrogen, C1-4 alkyl, phenyl, C2-5 alkoxy-carbonyl or nitrile,… R<8> stands for hydrogen or C1-4 alkyl, and… … … (a) R<9> and R<10> taken together form a chemical bond and X is an anion or … (b) R<10> is hydrogen then X represents -SO3<(-)> attached to the molecule in place of R<9>. … …<??>The compounds of the formula I have anti-asthmatic activity.

Description

and X represents a chlorine atom, optionally a compound of formula IV, wherein Me represents sodium, potassium or ammonium ions and X represents halogen, perchlorate, fluoroborate, nitrate, tipcyanate, azide, cyanate or react with hydrogen sulphithion.

The compounds of the formula I are intermediates of therapeutic drugs.

a bonded SO ₃ group, such that a pyrido [1,2-a] pyrimidine derivative of formula II wherein R ¹ , R ² , R ⁶ , R ⁷ , and R ⁸ is as defined above ( Azomethine of formula III, wherein R ³ , R ^4, and R ⁵ are as defined above, and the 2,4,8-triazafenalenium salt of formula I, wherein R ¹ -R ⁸ are as defined above, R ⁹ and R ¹⁰ together are a valence

The present invention relates to novel 2,4,8-triazafenalenium salts, their geometric and optical isomers, and processes for their preparation. These compounds are intermediates for human therapeutic drugs.

The 2,4,8-triazafenalenium salts are so far unknown in the literature, so the compounds of this application are the first representatives of this novel ring system.

The novel compounds of the present invention are represented by Formula I wherein R ¹ is C 1-4 alkyl or phenyl; R ² is C 1 -C 4 alkyl; R ³ is 1-4; C 1 -C 6 alkyl or phenyl; R ⁴ is hydrogen, C 1-4 alkyl, or phenyl mono- or polysubstituted with C 1-4 alkoxy, or singly C 1-4 dialkylamino, halo, or; may be substituted by nitro; or R ³ and R ^{4 taken} together form a group of formula (V) wherein R ¹¹ is hydrogen or C 1-4 alkoxy; R ^s is hydrogen, C1-4 alkyl, or phenyl which may be substituted by C nip simpler or more C1-4 alkoxy, or mono C 1-4 dialkylamino, halogen, or nitro; with the proviso that R ⁴ and R ^{5 are} not simultaneously hydrogen, C 1-4 alkyl, or phenyl optionally substituted with C 1-4 dialkylamino, halogen, nitro, or one or more C 1-4 alkoxy; R ⁶ is hydrogen, C 1-4 alkyl; R ⁷ is hydrogen, C 1-4 alkyl, phenyl, C 2-5 alkoxycarbonyl, cyano; R ⁸ is hydrogen or C 1-4 alkyl; when R ⁹ and R ¹⁰ are taken together as a bond, X is halogen, perchlorate, fluoroborate, nitro; R, H, Thiocyanate, Azide, Cyanate, when R ¹⁰ is hydrogen then X is R ⁹ , the linked -SO ₃ ® group.

Compounds of formula (I) are prepared by reacting compounds of formula (II) with -!

wherein R ¹ , R ² , R ⁶ , R ⁷ and R ⁸ are as defined above - by reaction with azomethines of formula III wherein R ³ , R ⁴ and R ⁵ are as defined above and the resulting quaternary chloride is isolated in a manner known per se or the chloride ion is replaced by X® anion by addition of a compound of formula IV wherein Me is an alkaline or alkaline earth metal, ammonium ion, X is as defined above. The reaction is preferably carried out in an indifferent organic solvent, such as an aliphatic or aromatic hydrocarbon or chlorinated hydrocarbon, ethers, ketones, but most preferably acetonitrile or dioxane, at 20-100 ° C with equimolar reactant ratios or 20-100 mol% excess of azomethines of formula III. finally. The product is isolated, for example, by filtration or by crystallization after removal of the solvent.

The anion exchange is preferably carried out by mixing an aqueous solution of the quaternary chloride (I) and the salt (IV) at 0-25 ° C and isolating the precipitated product by filtration.

The starting compounds of formula (II) are prepared by reaction of known nitrogen-bridged compounds with phosgene-iminium chloride as described in Belgian Patent No. 873,193.

Preparation of azomethines of formula III from literature [R. W. Layer, Chem. Rev. 63, 489 (1963); R. Thiol: Bull. Soc. Chim. Francé 708 (1947)]. Optically active forms of the compounds of formula (I) are prepared by reaction of compounds of formula (II) prepared from optically active nitrogen-bridge compounds with azomethines.

Our process also includes the preparation of geometric isomers of the compounds of formula (I). Geometric isomers are possible when R ⁸ is C 1 -C 4 alkyl, or X is SO ₃ R ⁴ attached to R ⁹ and R ¹⁰ is hydrogen. The rate of formation of the geometric isomers depends on the reaction conditions employed. Thus, under the reaction conditions indicated above, a mixture of geometric isomers is usually obtained which may be separated, if desired, for example by fractional crystallization or chromatography. The following examples further illustrate the process without limiting the invention to the examples.

Example 1

Ethyl 9 (8H) - [(N, N-dimethylamino) chloromethylene] -6,7-dihydro-6-methyl-4-oxo-4H-pyrido (0.01 mol, 3.25 g) [1,2-a] Pyrimidine-3-carboxylate was dissolved in 30 ml of anhydrous acetonitrile and then 0.01 mol (1.19 g) of benzylidenemethylamine was added. The reaction mixture was refluxed for 3 hours, during which two-thirds of acetonitrile was distilled off at atmospheric pressure, the residue crystallized on inoculation, filtered, washed with acetonitrile and air-dried. There were thus obtained 0.009 moles (4.00 g) of 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11,11-tetrahydro-2,9-dimethyl-7-oxo-7H-2,4, 8-Triaza-phenalenium chloride is obtained. M.p. 232 ° C

183,330 (ethanol). In the product, the triple phenyl group is in trans position with the methyl group at the nine position.

Analysis Calculated for C _{2 3 29} Η € 1Ν Ο ₃ O _4: C, 62.08%; H, 6.57%; N: 12.59%;

Found: C, 61.89; H, 6.58%; N: 12.31%. Δ Hnmr (CDCl ₃ ): 1.29d (3H); 1.33t (3H); 1.8-3.1m (4H); 3.27s (3H); 3.73s (6H); 4.25q (2H); 5.00m (1H); 6.8-7.2m (5H);

8.27s (1H); 9.73s (1H).

¹³ Cnmr (CDCl ₃ ): 7-C 161.4; IIb-C 154.4; 5-C 148.9; 10 1 -C 148.5; Ar-C 135.0, 129.1 128.7,

124.4; 6-C 106.5; IIa-C 85.7; 3-C 74.8; 9-C 46.6; 2-Me, NMe ₂ 42.3; 10-C 25.3; 11-C 18.5; 9-Me 15.2

6-COOEt 161.2 61.1 13.9.

Example 2

Ethyl 9 (8 H) - [(N, N-dimethylamino) chloromethylene] -6,7-dihydro-6-methyl-4-oxo-4 H -pyrido [0.01 mol (3.25 g)] , 2-a] pyrimidine-3-carboxylate was dissolved in 50 ml of anhydrous acetonitrile and then 0.01 mole (1.19 g) of benzene was added.

Example- song R ¹ R ² R ³ R ' R ^s R ⁶ R ⁷ R ⁸ Molecular formula Product obtained (I) ,, Recrystallization Elemental analysis (%) ^ ^Arrl Calculated solvent CH 1 Found N 4 Me Me et Ph H H COOEt Me C ₂₄ H ₃₁ C1N ₄ O ₃ 90 219 et 62.80 6.81 12.21 62.63 6.80 12.16 5 Me Me Me Ph H H COOEt Me c „h _{! 3} cin ₄ o ₃ 96 242 et 66.85 6.40 10.75 66.80 6.50 10.70 6 Me Me i-Pr Ph H H COOEt Me C "H _{) 3} ClN ₄ O ₃ 80 217 THE 63.48 7.03 11.85 63.26 6.91 11.81 7 Me Me pr Ph Me H COOEt Me 6 ₅ C1N ₄ O ₃ 90 170 THE 64.12 7.25 11.50 64.30 7.30 11.20 8 Me Me Me Ph H H COOEt Me c ₂₄ h ,, cin ₄ o ₄ 95 220 et 60.69 6.58 11.80 60.58 6.56 11.70 9 Me Me Me Ph Me H COOEt Me C _J4 H ₃₁ C1N ₄ O ₃ 95 207 THE 62.80 6.81 12.21 62.96 6.79 12.13 10 Me Me Me Ph H H COOEt Me C _2s H _J4 C1N _s 0 ₃ 97 210 et 61.53 7.02 14.35 61.42 7.18 14.42 11 Me Me Me Ph H H COOEt Me C _{2 6} H ₃ 5 C1N ₄ O ₆ 65 190 et 58.37 6.59 10.47 58.17 6.53 10.46 12 Me Me et i-Pr H H COOEt Me C ₂₁ H ₁₃ ClN ₄ 0 ₃ 84 150-158 THE 59.35 7.83 13.18 59.30 7.78 13.36 13 Me Me Me i-Pr H H COOEt Me c ₂₀ h _3I cin ₄ o ₃ 80 116 THE 58.45 7.60 13.63 58.29 7.58 13.60 14 Me Me Me Ph H H CN Me C ₂ .H ^ CINjO 97 252 THE 63.40 6.08 17.60 63.36 6.31 17.50 15 Me Me Me Ph Me H CN Me C ₂₂ H, ₆ C1N _S O 93 217 Ac 64.14 6.36 17,00 64.00 6.39 17.03 16 Me Me Me i-Pr H H CN Me C ₁₈ H ₂₆ C1N ₅ O 87 194 et 59.41 7.20 19.23 59,36 7.09 19.18 17 Me Me Me Ph H H Ph Me c ₂₆ h., cin ₄ o 83 169 V 69.56 6.50 12.48 69.51 6.71 12.31 18 Me Me Me Ph H H H Me c _2O h ₂₅ cin ₄ o 86 240 et 64.42 6.75 15.03 * 88 (Me Me Me H Ph H H Me) 64.38 6.74 15.19 * 12 19 Me Me Me Ph H Me et Me c ₂₃ h ,, n ₄ cio 62 163 Ac 66.57 7.52 ' 13.50 * 90 (Me Me Me H Ph Me et Me) 66.32 7.48 13.29 * 12 20 Me Me Ph Ph H H COOEt Me c ₂₈ h ₃₁ cin ₄ o ₃ 80 190 Ac 66.33 6.16 Mac, 05 66.48 6.08 11.09 21 Ph Me Me Ph H H COOEt Me ^ "Η, ^ ΙΝ, Ο, 72 113 Ac 66.33 6.16 11.05 66.17 6.24 11.19 22 Me Me Me Ph H H COOEt H C ₂₂ H ₂₁ C1N ₄ O ₃ 93 218 Ac 61.32 6.31 13.00 (V) á iltaláno > s formula : group 61.28 6.27 13.03 23 Me Me R ^{1 1} = OMe H H COOEt Me C ₂₆ H ₃₃ C1N ₄ O _s 80 161 Ac 60.40 6.43 10.84 (V) ltaláno s formula group 60.31 6.40 10.81 24 Me Me R ¹¹ = OMe H H CN Me C ₂₄ H ₂₈ C1N _s O ₃ 88 126 et 61.34 6.81 12.21 61.19 6.96 12.10

Et = ethanol, A = acetonitrile, Ac = acetone, V = water, x = isomer ratio

-3183 330 lidene methylamine. The reaction mixture was kept at room temperature for two days and then concentrated in vacuo at 20 ° C. The resulting oil was crystallized with diethyl ether, filtered and washed with ether to give 0.0093 mol (4.13 g) of 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11,11-tetrahydro-2 A mixture of diastereomers of 9-dimethyl-7-oxo-7H-2,4,8-triaza-phenalenium chloride is obtained which is a 1: 1 mixture of geometric isomers, relative to the relative position of the triple phenyl group and the nine position methyl group. Mp: 227 ° C.

1 H NMR (CDCl ₃ , cis-trans isomer): 1.26d (3H); 1.3 (3H); 1.8-3.1m (4H); 3.29s (3.22s) (6H); 3.70s (3.64s) (3H); 5.00m (1H); 6.8-7.2m (5H);

8.26s (8.22s) (1H); 9,74s (9,69s) (H).

Analysis calculated for C2 ₃ H ₂₉ C1N ₄ O ₃ O: C, 62.08%; H, 6.57%; N: 12.59%;

Found: C, 62.19%; H, 6.51%; N: 12.49%.

Example 3

0.01 mol (3.25 g) of optically active (-) - ethyl-9 (8H) - [(N, N-dimethylamino) chloromethylene] -6,7-dihydro-6-methyl-4-oxo Starting from the 4H-pyrido [1,2-a] pyrimidine-3-carboxylate, all procedures were carried out as in Example 1 to give (-) - 1-dimethylamino-6-ethoxycarbonyl (0.0090 mol, 4.00 g). -3-Phenyl-3,9,10,1-tetrahydro-2,9-dimethyl-7-oxo-7H-2,4,8-triaza-phenalenium chloride is obtained.

M.p .: 182-188 ° C (methyl ethyl ketone), ^[5 αβ = (-) 212.6 ° Analysis Calculated for C ₂ H ₃ O _{2 9} C1N ₃ O _4: C, 62.08%; H, 6.57%; N: 12.59%;

Found: C, 62.17%; H: 6-37%; N: 12.45%.

General rule 4-24. examples

Table 1 R ^1, R ^2, R ^6, R ⁷ and R ⁸ substituents corresponding α-chloro-enamine was dissolved in 50 ml of anhydrous acetonitrile, was added 0.01 mole of the table R ^3, R ^4, 0.01 M corresponding azomethine R ⁵ substituents. The reaction mixture is refluxed for two hours, during which two-thirds of acetonitrile is distilled off under atmospheric conditions, if the residue does not crystallize upon inoculation, the product is crystallized by digestion with diethyl ether, filtered, washed with ether and air dried. The compounds prepared are listed in Table 1.

The ratio of trans and cis isomers of the product prepared in Example 18 was determined by the intensity of the signal at the 9-position methyl groups at 1.32 ppm and 1.23 ppm. The ratio of trans and cis isomers of the product prepared in Example 19 was determined from the intensity of the signal of the methyl groups at the 3.71 ppm and 3.66 ppm positions.

General rule 25-32. examples

0.01 mole (4.44 g) of 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,111,11-tetrahydro-2,9-dimethyl-7-oxo-7H-2, 4,8-Triazafenalechloride is dissolved in 15 ml of water and added dropwise to a solution of the quaternary salt in a 20% solution of the corresponding anion-containing alkali salt until no further precipitate has formed. The precipitate was filtered off, washed with water and air dried. All of the above applies even if the starting quaternary chloride is in the order of 4 to 24. was one of the examples.

Example 25

When potassium iodide is used as the compound of formula (IV), 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11,11-tetrahydro-2,9-dimethyl-7-oxo is used. 7H-2,4,8-triazafenalenium iodide is obtained. M.p. 238-242 ° C, yield 96%.

Calcd for the C ₂₃ H ₉ IN ₂ O ₃ O _4: C, 51.47; H, 5.44; N: 10.44%;

Found: C, 51.40%; H: 5.60%; N, 10.79%.

Example 26

When sodium perchlorate is used as the compound of formula (IV), 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11-tetrahydro-2,9-dimethyl-7-oxo-7H -2,4,8-triaza-phenalenium perchlorate is obtained.

190-192 ° C, yield 92%.

Elemental Analysis calculated for C ₂ H ₃ O _{2 9} C1N ₄ O _7: C, 54.28%; H, 5.47%; N: 11.01%;

Found: C, 54.20; H, 6.33%; N: 11.38%.

Example 27

When sodium fluoroborate is used as the compound of formula (IV), 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11-tetrahydro-2,9-dimethyl-7-oxo- ⁷ H -2,4,8-triaza-phenalenium fluoroborate is obtained.

M.p. 246 ° C, yield 90%.

Elemental Analysis for: C ₂₃ H ₂₉ BF ₄ N ₄ O ₃ Calculated: C, 55.66; H, 5.89; N: 11.29%;

Found: C, 55.32%; H, 6.01%; N: 11.40%.

Example 28

When potassium nitrate is used as a compound of formula (IV), 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11,11-tetrahydro-2,9-dimethyl-7-oxo is used. 7H-2,4,8-triaza-phenalenium nitrate is obtained.

M.p. 232 ° C, yield. 65%.

Analysis for the C ₂₃ H ₉ N ₂ O ₅ Calculated _O6: C, 58.59%; H, 6.19%; N: 14.85%;

Because; C: 58.60%; H, 6.23%; N, 14.59%.

Example 29

When potassium cyanate is used as the compound of formula (IV), 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11,11-tetrahydro-2,9-dimethyl-7-oxo is used. 7H-2,4,8-tiaza-phenalenium cyanate is obtained.

M.p. 193-196 ° C, yield 78%.

Analysis Calculated for C ₂₄ H ₂₉ N O _S O _4: C, 63.85%; H, 6.47%; N: 15.51%;

Found: C, 63.51%; H, 6.72; N, 15.38%.

Example 30

When ammonium thiocyanate (IV) is used, 1-dimethylamino-6-ethoxy-41

183,330 Carbonyl-3-phenyl-3,9,10,11-tertrahydro-2,9-dimethyl-7-o-o-7H-2,4,8-triaza-phenalenium thiocyanate is obtained.

M.p. 242 ° C, yield 72%.

Calcd for C24H29N5O3S: C, 61.65; H, 6.25%; N: 14.98%;

Found: C, 61.10%; H, 6.20%; N, 14.59%.

Example 31

When sodium azide is used as the compound of formula (IV), 1-dimethylamino-6-ethoxycarbonyl-3-phenyl-3,9,10,11-tetrachydro-2,9-dimethyl-7-oxo 7H-2,4,8-triaza-phenalenium azide is obtained.

M.p. 186 ° C, yield 92%.

Elemental analysis based on the formula C23H29N7O3

Calculated: C, 61.19; H, 6.47%; N: 21.72%;

Found: C, 61.30; H, 6.10%; N, 21.07%.

Example 32

When sodium hydrosulfite is used as the compound of formula IV, anhydro-3-phenyl-3,5,6,9,10,11-hexahydro-6-ethoxycarbonyl-2,9-dimethyl-5-sulfo-7-oxo 7H-2,4,8-triaza-phenalenium hydroxide is obtained.

Mp 210 ° C, 80% yield.

Elemental analysis for C23H30N4O6S:

calculated:

Because:

C: 56.32%; C: 56.79%;

H, 6.16%; H, 6.01%;

N: 11.42%; N, 11.72%.

General rule on pages 33-37. examples

0.01 mole for a solution of a-chloroenamine corresponding to the substituents R ¹ , R ² , R ⁶ , R ⁷ and R ^{8 in} 50 ml of anhydrous acetonitrile in Table ² , 0.01 mole for R ³ , R ⁴ and R Azomethine corresponding to its ⁵ substituents. The reaction mixture is refluxed for two hours and then two-thirds of acetonitrile is distilled off under atmospheric conditions. The reaction mixture was cooled to 0 ° C. The precipitated product is filtered off and crystallized from the solvent shown in Table 2.

In Examples 33, 35, 36 and 37, a mixture of diastereomers was formed, the ratio of which was determined by 5-H or signal intensity using ¹ H-NMR spectroscopy of images in CDCl ₃ solution. The 5-H signal is 9.63 ppm for the trans isomer of the product prepared in Example 33 and 9.72 ppm for the cis isomer; the trans isomer of the product prepared in Example 35 at 9.48 ppm and the cis isomer

9.59 ppm; the trans isomer of the product prepared in Example 36 at 9.70 ppm and the cis isomer

It was reported at 9.80 ppm. For the product prepared in Example 37, the isomer ratio was determined from the intensity ratio of the dimethylamino group at 3.17 ppm and 3.23 ppm.

R ² R ³

example Number

R ¹

R ⁴

Resultant product (I) rs rt rs x Recrystallize- Elemental analysis.

formula calculation! Calculated / Found ^zo j ^nei 'solvent C Η N ^gold

33rd Me Me Me 4-MeOPh H H COOEt Me cl C ₂₄ H ₃₁ C1N ₄ O ₄ 95 220 66.85 6.57 11.79 80 Me Me Me H 4-MeOPh H COOEt Me cl 67.02 6.55 11.70 20 34th Me Me Me 4-Me ₂ NPh H H COOEt Me cl C ₂₅ H ₃₄ C1N _S O ₃ 90 208 THE 61.52 7.02 14.35 61.41 7.10 14.42 35th Me Me Me 4-NO ₂ Ph H H COOEt Me cl C ₂₃ H ₂₈ C1N _S O ₅ 92 205 et 56.38 5.76 14.29 55 Me Me Me H 4-NO ₂ Ph H COOEt Me cl 56.18 5.82 14.34 45 36th Me Me Me 4-ClPh H H COOEt Me cl 57.62 5.88 11.68 80 Me Me Me H 4-ClPh H COOEt Me cl C ₂₃ H ₂₈ C1 ₂ N ₄ O ₃ 82 208 THE 57.85 5.72 11.70 20 Me Me Me 2,4,6 37th Me Me Me - (MeO) ₃ Ph H H 2,4,6 H COOEt Me cl {- · 2 6 H 3 5 CIN ₄ O ₆ 65 213 Et 58.37 6.59 10.47 67 - (MeO) ₃ Ph H Cooee Me cl EtAc 58.12 6.65 10.52 33

A = acetonitrile; Et = ethanol; Et-EtAc = ethanol-ethyl acetate

Claims (4)

Claims 60 A process for the preparation of 2,4,8-triazafenalenium salts of the formula I and their geometric and optical isomers, wherein R ¹ is C 1 -C 4 alkyl or phenyl; R ² is C 1-4 alkyl; R ³ is C 1-4 alkyl or phenyl; R ⁴ is hydrogen, (C 1 -C 4) alkyl, or phenyl, singly or multiply substituted by (C 1 -C 4) alkoxy, or (C 1 -C 4) dialkylamino, halo, or nitro; -5183 330 may be substituted; or R ³ and R ^{4 taken} together form a group of formula (V) wherein R ¹¹ is hydrogen or C 1-4 alkoxy; ^R5 is hydrogen, C1-4 alkyl, or phenyl C1-4 alkoxy, or mono C 1-4 dialkylamino, halogen, or nitro groups may be mono- or poly-substituted; with the proviso that R ⁴ and R ⁵ are not simultaneously hydrogen, or C1-4 alkyl optionally substituted with one C1-4 alkyl dialkylamino, halogen or nitro, or one or more C1-4 alkoxy; R ⁶ is hydrogen, C 1-4 alkyl; R ⁷ is hydrogen, C 1-4 alkyl, phenyl, C 2-5 alkoxycarbonyl, cyano; R ⁸ is hydrogen or C 1-4 alkyl; if R ⁹ and R ¹⁰ together represent a bond, X is a halogen, perchlorate, fluoroborát-, nitrate, thiocyanate, azide, cyanate, when R ¹⁰ is hydrogen, then X is linked to R ⁹ SO ₃ group in place Characterized in that a pyrido [1,2-a] pyrimidine derivative of the formula (II) in which R ¹ , R ² , R ⁶ , R ⁷ and R ⁸ is as defined above (III); with azomethine of the formula wherein R ³ , R ⁴ and R ⁵ are as defined above, and the resulting 2,4,8-triazafenalenium salt of formula (I) wherein R ¹ -R ⁸ is as defined above, R ^{9 0} and R ¹ together form a bond and X is H; chlorine, optionally with a compound of formula (IV) wherein Me represents sodium, potassium or ammonium ions and X represents halogen, perchlorate, fluoroborate, nitrate, thiocyanate, azide, danate or hydrogen sulfition. ; The process of claim 1, wherein the 2,4,8-triazafenalenium salts of formula (I) wherein R ⁴ -R ⁸ are as defined in claim 1, together R ⁹ and R ¹⁰ form a bond, X for the preparation of a chlorine atom, characterized in that a pyridopyrimidine derivative of the formula (II) in which R ¹ , R ² , R ⁶ , R ⁷ and R ⁸ is as defined in claim 1 is represented by an azomethine of the formula (III) wherein R ³ , R ⁴ and R ⁵ are as defined in claim 1 in the presence of a solvent. 0 3. A process according to any one of claims 1 and 2 wherein the 2,4,8-triazafenalenium salts of the formula (I) wherein R ¹ -R ⁸ are as defined in claim 1, together R ⁹ and R ¹⁰ form a bond. , X represents a chlorine atom Characterized in that a pyridopyrimidine derivative of formula (II) wherein R ¹ , R ² , R ⁶ , R ⁷ and R ⁸ are as defined in claim 1 is an azomethine of formula (III) wherein R ³ And R ⁴ and R ⁵ are as defined in claim 1 at a temperature of from 0 ° C to 100 ° C, preferably from 60 ° C to 85 ° C. A process for the preparation of the 2,4,8-triazafenalenium salts of the formula (I) according to claim 1 wherein R ¹ -R ⁸ are as defined in claim 1, X is halogen, perchlorate, fluoroborate, nitrate, thiocyanate, azide, cyanate, in which case R ⁹ and R ¹⁰ together form a bond, or X is linked to R ⁹ in place -S0 ₃ 'group, in which case R ¹⁰ is hydrogen, wherein an X is chlorine a 2,4,8-triazafenalenium salt of formula I wherein R ¹ -R ⁸ are as defined in claim 1, R ⁹ and R ^{19 are taken} together to form a single bond, and a compound of formula IV wherein Me and X are as defined in claim 1 in the presence of a solvent, preferably water.