DE2854113A1 - CONDENSED PYRIMIDINE DERIVATIVES AND METHOD FOR PREPARING THE SAME - Google Patents

Description

/ Ib

rf D :. - te

bf; s =

li- ^! -.i ^ .- ,: t ^ i, -i: h-cß3 3

D-6000 Frankfurt / Main 1 Telephone: 0611/55 50 61

Ffm, December 14, 1978

Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Rt.

To utca 1-5

H-1045 Budapest IV, Hungary

CONDENSED PYRIMIDINE DERIVATIVES AND METHODS TO MAKE THE SAME

The present invention relates to novel nitrogen-containing condensed compounds and. Method of manufacture the same.

It is already known that 2-Methy1-4-oxo-6,7,8,9- -tetrahydro-4H-pyrido / 1,2-a7pyrimidine-9-carboxylic acid derivatives are produced by the catalytic hydrogenation of the corresponding unsaturated compounds can be. / 3, Het. Chem. 13, 797/1976/.J ⁷

A 1499-77

909828/0652

ORIGINAL INSPECTED

-A-

The new compounds can be made by the general formula

To be defined·

In the formula I stands

R for hydrogen or C,. Alkyl, R ¹ for hydrogen or C,. Alkyl.

R and R together form a group of the formula

- (CH = CH) ₂ - which is bonded to the two adjacent ring carbon atoms, and the dashed line represents a hyphen,

R ² means hydrogen or alkyl with 1-4 carbon atoms,

R ^y denotes hydrogen, alkyl with 1-4 carbon atoms, phenyl, carboxy, or its alkali metal salt, alkoxycarbonyl with 1-4 carbon atoms in the alkyl part, carbamoyl, cyano, -CO-IJH-CO-IIH-SO ₂ -CcH.- CH,

or - (CH ₀ ) -COOR ¹ * -, where s = 1-3 and R ¹ * is hydrogen or alkyl with 1-4 carbon atoms and

η ^s 0 or 1,
a / if R ¹ 'is hydrogen and R and R and R ⁹ and R together form a hyphen,

Y stands for an oxygen or sulfur atom deprived of its outer electron pair,

ORiGiNAi INSPECTED

909828/0652

and in this case, R ⁷ and R ^{8 represent} a lone pair of electrons or

Y stands for a nitrogen atom deprived of its outer electron pair.

R denotes alkyl with 1-4 carbon atoms, optionally substituted aryl with 6-10 carbon atoms, or aralkyl with 7-12 carbon atoms, R denotes a lone pair of electrons or C ₁

Alkyl and in the latter case a halide _λ ¹ On forms a salt with the positive nitrogen atom, R, Rj ⁷ means halogen or

X stands for an oxygen or sulfur atom that has been deprived of its outer pair of electrons,
R ^ means hydrogen or CL. Alkyl, R ⁵ and R represent a lone pair of electrons or

X stands for one that is deprived of its outer electron pair Nitrogen atom,

R ⁴ denotes chloroacetyl, alkyl with 1-4 carbon atoms, optionally substituted aryl with 6 * 10 carbon atoms, or an optionally substituted heteroaryl,
R ^ represents hydrogen or alkyl and R represents

a lone pair of electrons or b / if R ¹² and R ^{15 form} a hyphen and R ¹¹ stands for hydrogen and R ³ and R together form a bond

4. ζ 6 dash then the definition of K *, R ^, R,

R ⁷ , R ⁸ , X and Y as indicated in point a /, and c / if R ¹⁰ and R ¹¹ and R ¹² and R. form a hyphen together, then

Y means a pair of electrons deprived of its outer pair Oxygen or sulfur atom, and if

E ⁷ , R ⁸ and R ⁹ mean a lone pair of electrons, then a positive cation forms a salt with the anion thus formed, or
R ⁸ and R ^{9 represent} a lone pair of electrons, R be

909828/0852

ORIGINAL INSPECTED

2864113

indicates hydrogen or alkyl with 1-4 carbon atoms or

Y means one that is deprived of its outer electron pair Nitrogen atom,

R ^c denotes hydrogen, alkyl with 1-4 carbon atoms, optionally substituted aryl with 6-10 carbon atoms,
R stands for alkyl with 1-4 carbon atoms and

R means a lone pair of electrons, 10 X / R ⁵ , R ⁶ , ¹ egg, ¹ J stands for halogen, or

X stands for one that is deprived of its outer electron pair

Oxygen or sulfur atom, and if

4 5 6

R, R 'and R mean a lone pair of electrons, forms a positive cation with the anion thus formed a sale, or.

R * means hydrogen or alkyl with 1-4 carbon atoms,

R ^ and R stand for a lone pair of electrons or X stands for a nitrogen atom deprived of its outer electron pair, and

R ⁴ represents chloroacetyl, alkyl with 1-4 carbon atoms, or optionally substituted aryl with 6-10 carbon atoms or optionally substituted heteroaryl,

r5 means hydrogen or alkyl with 1-5 carbon atoms, and

R ⁶ stands for a lone pair of electrons, and if Y and X stand for an oxygen or sulfur atom deprived of its outer electron pair and R, R, R ^ »R ⁸ and R ^ mean a lone pair of electrons, Y and X for one deprived of their outer electron pair Nitrogen .etehen, and

R ⁶ and R ^ represent a lone pair of electrons and R ⁵ and R ^{8 represent} hydrogen or alkyl with 1-4 carbon atoms, then

909828/0652 original inspected

R and R together form an optionally substituted - (CH ₂ ) ₈ in which ο = 1, 2, 3 or 4.

• Those compounds are particularly preferred of the general formula I in which η = 1, R is hydrogen,

5 R hydrogen or alkyl with 1-4 carbon atoms, beäon-

2
ders methyl, R ^c hydrogen or alkyl with 1-4 carbon

3
atoms, R ^ is carboxy, methoxy carbonyl, JSthoxy carbonyl or carbamoyl.

The invention also relates to a process for the preparation of the compounds of the general formula

optically active antipode, and salts thereof, characterized in that he

a compound of the general formula

CX, - '

R 'ο

wherein R, R ¹ , R ² , R ⁵ and η are as indicated above, a -, / with a dihalomethylene ammonium halide of the general formula III

»\ Φ / ^ Z e

N = C. A.

where ELg stands for halogen,

909828/0652

ORIGINAL INSPECTED

R is alkyl with 1-4 carbon atoms, or optionally substituted aryl with 6-10 carbon atoms, R is alkyl with 1-4 carbon atoms or A is an anion,
and thereby a compound of the general formula

^Λ * ~ ' ⁷ "i Il ^Ia

R. '

wherein R, R ¹ , R ² , R ⁵ , R ¹⁵ , R ¹⁶ , α, η and the dashed line are never as indicated above - or

15 a ₂ / with a carbon disulfide of the formula

CS ₂ IV

preferably, converts in the presence of alkali ions and thereby a compound of the general formula

Ib

25 ^ O

wherein R, R ¹ , R ² , R ⁵ , n, HIg and the dashed line are as indicated above, -and ^ means an alkali * on - contains,

or

a »/ with an isocyanate of the general formula R ¹⁷ - N * C = VV

converts - in which R ^{17 represents} alkyl with 1-4 carbon atoms, chloroacetyl, optionally substituted aryl with 6-10 carbons

909828/0652

ORlGlNAi INSPECTED

ZTj

Means substance atoms or optionally substituted aryl, and

V stands for oxygen or sulfur atom and thereby compounds of the general formula

Ic

obtained, wherein R, R ¹ , R ² , R ⁵ , R ¹⁷ , V, η and the dashed line as indicated above aind -

and, if desired, that obtained by one of the above methods Compound of the general formula Ia, Ib or Ic into another compound of the general formula Ia, Ib, Ic or I converted and, if desired, in a compound obtained of the general formula I a substituent R, R, R,

R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , X or Y into another R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ , X or Y converted in any order and / or converted into a pharmaceutically suitable salt or released from their salts and / or, if desired, a racemate of the general Formula I resolved.

It has now surprisingly been found that the methylene group of the compound of general formula II the is in the / ^ position in relation to the nitrogen atoms, Contains active hydrogens that are involved in electrophilic substitution reactions can participate.

Part of the compounds of general formula I. shows valuable biological activity, another part can be used as starting material for the production of valuable biological

909828/0652

ORlGiNAL INSPECTED

-X-

¹¹ 28bA113

serve active connections. The compounds of general formula I prepared can exist in three tautomeric forms / see Figure Ij. It depends on the substituents present whether one of the tautomeric forms occurs predominantly, or possibly 2 tautomeric forms. Forms under given circumstances form an equilibrium mixture in an amount also proven by spectroscopic methods, a ZE geometric isomerism is also possible between the individual tautomeric forms. The present invention also includes the possible geometric isomers and the racemic or optically active forms of the compounds of the general formula I.

When executing the variant a ^ / the connection of the general formula II, if appropriate dissolved in an inert solvent, for the solution of the dihalo-methylene ammonium halide in an inert solvent is added and the reaction mixture is heated to complete the reaction. to finish quantitatively. When isolating the compounds of the general formula Ia, the reaction mixture is preferred concentrated under reduced pressure and the residue is crystallized.

In process variant a ·, / hydrocarbons, preferably benzene, toluene, xylene, chlorinated hydrocarbons, preferably chloroform, dichloromethane, chlorobenzene, etc., are suitable as inert solvents. The reaction is preferably conducted at 0 - 120 ⁰ C performed - 10§C, especially at 10th

The compound of the formula Ia formed can also be reacted without isolation, for example with an amine, and converted into a

30 compound of the general formula I are converted.

Process variant a ₂ / is preferably carried out in such a way that an alcoholic solution of alkali metal hydroxide is added dropwise to the alcoholic solution of the compound of the general formula II and the carbon disulfide of the formula IV with mild external cooling and the reaction mixture

909828/0652

ORlGJNAl INSPECTED

2854119

Figure 1.

909828/0652

ORIGINAL INSPECTED

preferably at room temperature. The during the Compounds of the general formula Ib formed in the reaction can, if desired, by removing the solvent can be isolated under reduced pressure. The compounds of general formula Ib can also without isolation, for example. under Use of alkylating agents in the compounds of general formula I are converted.

The alcohols used can be methanol, ethanol, n- or iso-propane, or n-butanol. Sodium or potassium hydroxide are suitable as alkali metal hydroxides. The reaction may preferably carried out at 0 to 120 ⁰ C are performed. 1-5 moles of carbon disulfide of the formula IV can be used for 1 mole of the compound of the general formula II.

In process variant a * /, a compound of the general formula II is reacted with isocyanate of the general formula V without a solvent or in the presence of an inert solvent. If one works in the presence of a solvent, the compound of the general formula Ic formed separates out of the reaction mixture and can be removed by filtration. If the compound of the general formula Ic formed does not precipitate from the mixture, the reaction mixture is concentrated under reduced pressure and the residue obtained is recrystallized from a suitable solvent. If you work without a solvent, the reaction mixture can be recrystallized from a suitable solvent after the reaction has ended. The reaction is carried out at 0 25O ⁰ C. The reaction temperature depends on the starting materials.

One uses the for every mole. Compound of the general formula II 1-3 mol of the isocyanate of the general Formula V.

909828/0652

ORlGlNALiNSPECTED

A compound of the general formula I in which R, R, R, R->, _n and the dashed line are as indicated above, R ¹⁰ and R ¹¹ , and R ¹² and R ¹³ together form a hyphen, X and Y a sulfur atom mean and R, R, R, R, R, R ^y mean a lone pair of electrons and an alkali metal! Cation forms a salt with the dianion that forms

a / reacted with an alkylating agent, and such a compound of the general formula I is obtained, wherein R, R ¹ , R ² , R ⁵ , η and the dashed line are as indicated above, R ^ and R and R and R ¹² together form a hyphen, R ³ signifies hydrogen, X and Y signify a sulfur atom, R, R, R ^,

Q a

R represents a lone pair of electrons, R represents alkyl with 1-4 carbon atoms. As an alkylating agent the usual reagents can be used.

You can for example. Alkyl halides e.g. Methyl iodide, ethyl bromide, etc., aralkyl halides e.g. Benzyl chloride etc. Dialkyl sulfates, e.g. Dimethyl sulfate, diethyl sulfate, trialkyl phosphates, e.g. Triethyl phosphate, benzenesulfonic acid and p- -Toluenesulfonic acid, -alkyl ester, trialkyl-o; conium fluoroborate and use other common alkylating agents.

The reaction can preferably be carried out ^{at 0-160 °} C. in the presence of a solvent. The solvents customary in the alkylation and aralkylation reactions are used as solvents. To 1 mole of the compound of general formula I are preferably used 0,3 - 2,0 moles of alkylating or aralkylating · ^T he molar ratio of the reagents may be used if desired in a different ratio;. *

909828/0652

ORIGINAL INSPECTED

Ζϊ

' . 2654113

b / reacted with an alkylene dihalide, and one

obtains those compounds of the general formula I in which R, R ¹ , R ² , R ³ , η and the dashed line are as indicated above, R ¹⁰ and R ¹¹ and R ¹² and R ¹⁵ together form a hyphen, X and Y sulfur

C C QQ

mean, R, R, R, Br mean a lone pair of electrons and R ⁴ and R ⁷ together form - (CH ₂ ), where s = 1, 2, 3 or 4.

The reaction is preferably carried out under the circumstances indicated in point a /.

A compound of the general formula I, wherein

R, R, R, R *, η and the dashed line are as above

Q in 11 IP indicated, R ^ and R and R and R together form a « Hyphen and R ^ stands for hydrogen, X and Y mean

R f \ 7 ft

a sulfur atom, R, R, R, R mean a lone Pair of electrons, R means alkyl with 1-4 carbon atoms » Will be aralkyl of 7-12 carbon atoms

a / reacted with an alkylating agent, preferably in the presence of an acid binder, and compounds of the general formula I are obtained - in which R, R, R, R, η and the dashed line are as indicated above, R and R and R and R together form a hyphen, X and Y _t represents a sulfur atom, and R **, R "R" R len depicting a lone pair and R and R are identical or different and denote alkyl having 1-4 carbon atoms.

As the alkylating agent, the above-mentioned reagents can be used. Used as an acid binder Alkali carbonate, alkali hydrogen carbonate, alkali hydroxide irialkylamine, alkali earth metal carbonate are preferred. The reaction can preferably be carried out in the presence of a solvent. The reaction circumstances become as above

909828/0652

ORlGJNAl INSPECTED

'285A113

specified selected;

b / heated with an acid anhydride and from 2 alkyl-S-CrS groups or from the group Ar ₈ Ikyl-SCS a 1,3-dithiethane ring is formed and a compound of the general formula Id is obtained

10, ·. _Id

where R, R, R% R ^, η and the dashed line like are given above.

Aliphatic acid anhydrides9zB are preferred as acid anhydrides. Acetic anhydride, propionic anhydride etc. are used.

The reaction is preferably carried out at the boiling point of the acid anhydride}

c / reacted with a diamine and man / such compounds

12 3 of the general formula I - in which R, R, R, R, η and the

25 dashed line as indicated above are R and R

and R '*' ² and R ^ together form a hyphen, X and Y represent an its outer electron pair Deprived nitrogen atom, R ⁶ and R ^ represents a lone pair of electrons, R and R atom is a hydrogen, or ^A lkyl of 1-4 Kohlenstoffatomben means, R and R together form a - (CHg) ₈ group, and s = 1, 2, 3 or 4.

909828/0652

ORIGINAL INSPECTED

A compound of the general formula I in which R »R» H, R, η and the dashed line are as indicated above, E ⁹ and,., R ¹⁰ and R ¹¹ and R ^{12 form} a hyphen, K ^{15 is} hydrogen, x / r ⁴ , R ⁵ , R ⁶ J represents halogen, Y represents a nitrogen atom deprived of its outer electron pair, R 'represents an alkyl with 1-4 carbon atoms, or optionally substituted aryl with 6-10 carbon atoms, R ^{8 represents} alkyl with 1-4 carbon atoms, means and a halide ion forms a salt with the po-

10 nitrogen atom - will

a / with an alcohol in the presence of an alkali alkanoate implemented and you get such a connection of the all-

• y ο -z

common formula I - in which R, R, R, R ^, η and the dashed line are as indicated above, and R * is hydrogen, R ⁹ and R ¹ and R ¹¹ and R ^{12 are} a hyphen, X and Y are his represents an oxygen atom deprived of the outer electron pair, R, R, R, <R represent a lone pair of electrons and R represents alkyl with 1-4 carbon atoms.

Aliphatic and aralkyl alcohols are suitable as alcohols. The preferred alkali alkanoates are salts of 'Alkali metals used with aliphatic carboxylic acids. Sodium acetate and potassium acetate can also be used as alkali -Alkanoate serve.

The reaction can preferably be carried out at 0-150 ° C,
b / reacted with a water- containing alcohol and such compounds of the general formula I are obtained - in which R, R ¹ , R ² »R ^» η and the dashed line are as indicated above, R 'is hydrogen atom, R and R ¹⁰ and R ¹¹ and R ^{12 form} a hyphen, X a nitrogen atom deprived of its outer electron pair

909828/0652

ORlGlNAl

3ο

-yr-

atom, Y represents an oxygen atom deprived of its lone pair of electrons, R ⁶ , R ⁷ , R ^{8 represent} a lone pair of electrons, R ⁴ denotes alkyl with 1-4 carbon atoms, optionally substituted aryl with 6-10 carbon atoms, R ⁵ denotes alkyl rait 1- 4 carbon atoms means

As alcohols, aliphatic alcohols are preferred. The reaction is preferably conducted at 0 -, preferably from 150 ⁰ C at the boiling point of the alcohol.

c / reacted with a primary or secondary amine, preferably in the presence of an inert solvent, and one receives such compounds of the general formula I - in

1 2 3
which R, R, R ^, R- ⁷ , η and the dashed line like

Q 10 11 IP are given above, R ^ and R and R and R denote a hyphen, R * denotes hydrogen, X and Y represent a nitrogen atom deprived of its lone pair of electrons, R ^ alkyl with 1-4 carbon atoms, optionally substituted aryl with 1 -4 carbon atoms, optionally substituted heteroaryl, R ^ is hydrogen or alkyl with 1-4 carbon atoms, R is a lone pair of electrons, R 'is alkyl with 1-4 carbon atoms, optionally substituted aryl with 6-10 carbon atoms, R ^{8 is} alkyl with 1-4 carbon atoms and a halide forms a salt with the positive nitrogen atom and, if desired, this base is released from the salt obtained and then those compounds of the general formula I are obtained in which R, R ¹ , R ² , R ³ , η and the dashed line as shown above

are given, R ¹⁰ and R ¹¹ and R ¹² and R ¹³ together form a hyphen and X and Y one of their electron pair; represent deprived nitrogen atom, RY / a.Bser-

909828/0652

ORlGiNAi. INSPECTED

28 ^Γ 4 \ 13

Substance atom, alkyl with 1-4 carbon atoms or optionally substituted aryl with 6-10 carbon atoms or optionally substituted heteroaryl, ir denotes hydrogen atom, or alkyl with 1-4 carbon atoms, R * denotes ⁷ alkyl with 1-4 carbon atoms or optionally substituted aryl with Represents 6-10 carbon atoms, R ^{8 represents} alkyl of 1-4 carbon atoms, R ^ and R ^ represent a lone pair of electrons.

The reaction is conducted at 0 - preferably performed at 160 G ⁰ to the boiling point of the inert solvent used. As an inert solvent, aromatic hydrocarbons, for example. Benzene, toluene, etc., halogenated hydrocarbons, e.g. Chloroform, carbon tetrachloride, chlorobenzene, etc. can be used.

1 mole of the starting compound requires 1-5 moles, preferably 1.9-2.9 moles of ammonia or amine.

The compound of general formula I obtained can be obtained by using a carbonate, alkali metal bicarbonate, 'Alkali hydroxide or trialkyl amine are released.

d / reacted with a diamine, preferably in the presence of an inert solvent, and such a compound of the general formula I is obtained in which R, R ¹ , R ² , R ⁵ , η and the dashed line are as indicated above, and R and R and R and R form a hyphen, X and Y represent nitrogen atom deprived of their lone pair of electrons, R and R ^{8 represent} hydrogen or alkyl with 1-4 carbon atoms and R ^ and R together represent a substituted group of the formula (CH ₂ ) _S form, where s = 2, 3 or

The reaction is carried out under the circumstances indicated in point c /.

909828/0652

ORIGINAL INSPECTED

- Xf-

In the specification, "alkyl of 1-4 carbon atoms" means a straight or branched alkyl group. The term "optionally substituted
Aryl with 6-10 carbon atoms "stands for an optionally mono- or polysubstituted phenyl

or naphthyl group, where the substituents are the same or can be different, * and for alkyl with 1-4 carbon atoms,

Alkoxy with 1-4 carbon atoms, amino, hydroxyl, Carboxylic acid, carboxylic acid derivative, nitro, or halogen. The alkoxy group with 1-4 carbon atoms includes straight or branched alkoxy groups. "The carboxylic acid derivative group is understood to mean Alkoxycarbonyl with 1-4 carbon atoms in the alkyl part, Nitrile, aminocarbonyl, which optionally

on the amino group by alkyl with 1-4 carbon

atoms, acyl with 1-4 carbon atoms ,. DialKylaminomethylene-amino may be substituted with 1-4 carbon atoms in the alkyl part or carbohydrazide. The term in the description "optionally substituted heteroaryl" includes monocyclic or bicyclic, identical or different heteroatoms optionally substituted by alkyl, nitro, alkoxy, amino or halogen containing compounds, such as. 2-, 3- or 4-pyridyl, Furyl, pyrimidinyl, pyrazinyl, pyridazinyl etc.

The heterocyclic compounds of the general formula II used as starting materials can be replaced by the in the Hungarian patents Nos. 156 119, 158 089, 162 384, 373, 166 577 and in Dutch patent application 7212286 Methods described are prepared, whereas the compounds of the general formulas III, IV and V and the au their preparation used commercially available reagents Products are.

909828/0652

ORIGINAL INSPECTED

1654119

The compounds of general formula I can be alkali metal salts on the carboxyl group, for example. Sodium or Potassium salts, ammonium salts, alkali earth metal salts, e.g. Potash or magnesium salts or with organic amines / e.g. Form triethylamine / salts.

The compounds of the general formula I can be used primarily as pharmaceutical intermediates. The compounds can be reacted with aryldiazonium salts and pyrido / l, 2-a7pyrimidine derivatives substituted by hydrazono groups in the 9-position, which have a number of pharmaceutical effects, for example. antiallergic We are sound-showing end products.

Some representatives of the compounds of general formula I are themselves PG antagonists, continue to show analgotic, antiarteriosclerotic, tranquilizer or others Effect.

If the compounds of general formula I are used as pharmaceutical active ingredients, depending on the area of application, a dose of 1-1500 mg per four times a day or in divided doses can be given to the patient.

The compounds of the general formula I can be formulated as dragees, tablets, suspensions, injections, capsules, powders, suppositories or in other forms, whereby disintegration-promoting and other carriers can also be added *

Further details of the invention can be found in the examples without restricting the invention to the examples.

909828/0652

ORIGlNM. INSPfiCTBÖ

39

5.9g 3-'A'thoxycarbonyl-6-eiq t hyl-4- oxo-6,7,8,9- -tetrahydro-4H-pyrido / r, 2-a7pyri ^ idin and 2.3 ml of carbon diulphide are dissolved in 35 n £ fo "ethanol and in the solution is. a solution of 2.8 g of potassium hydroxide in 25 ml of ethanol 25 - 30 C added dropwise. The reaction mixture is stirred for one hour at room temperature and evaporated under reduced pressure. £ an receives 9.8 g of 3-l "fchoxycarbonyl-6-methyl-9- / Tbiß-tiolat) -methylene7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido- / l, 2-a7 pyrimidine Dipotassium salt.

Example 2.

To a solution of 9.7 g of 3- * A * thoxycarbonyl-6-methyl- -9 - / (! Bis-tiolate) -methylene7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / L, 2-a7pyrimidin dipotassium salt, which was prepared according to example 1, in 60 ml of ethanol, is under external cooling, 4.7 ml of dimethyl sulfate was added dropwise and the reaction mixture is stirred for one hour at 40 ⁰ C. The yellow crystals which separate out are filtered off, washed with water and dried. 7.1 g / 6 % of 7 3-ethoxycarbonyl-6-methyl-9- - (methylthio-thiocarbonyl) -4-oxo-l, 6,7,8-tetrahydro-4H-pyrido2T, 2-a7pyrijnidine, the product melts after recrystallization from benzene at 198-199 ⁰ C.
Analysis for the formula ^c i4 ^H i8 ^N 2 ° 3 ^S 2 calculated: 0 51.51 #, H 5.56 $, N 8.58 4,

25 found: C 51.70 4, H 5.78 #, N 8.48 #.

Example 3 *

To a solution of 9 »7 g of 3-A ^# thoxycarbonyl-6- -methyl-9 - / (bis-t ⁷ iolate) -methyleneJ-4-oxo-6,7,8,9-tetrahydro- - ^ - pyrido ^ T ^ -a / py ^ imidine dipotassium salt, prepared according to Example 1, 4.7 g of ethylene bromide are added to 60 ml of 'ethanol, ^ as the reaction mixture is stirred for one hour at 40 0, and the precipitated sodium bromide is filtered

909828/0652

ORIGINAL INSPECTED

2864113

Half of the mother liquor is evaporated and the crystals which separate out after cooling are filtered and dried. 3 g of 3-ethoxycarbonyl-6-methyl-9- (1,3-dithiolane-2- -ylidene) -4-oxo-6,7,8,9-te trahydro-4H-pyridO2T, 2-a7pyrimidine are obtained, and the product melts after recrystallization from "A'thanol at 205 -.207 ⁰ C.
analysis

Calculated: C 53-23% H 5-36 #, N 8.27 4, • found: C 53.3.7 #, H 5.41 #, N 8.22 ü,

10 Example 4.

3 »26 g of 3-'ethoxycarbonyl-6-methyl-9- (methylthio-

-thiocarbonyl) -4-oxo-l, 6,7,8-tetrahydro-4H-pyrido2T, 2-a7-pyrimidine are boiled in 20 ml of acetic anhydride for 2 hours. After cooling, the precipitated crystals are filtered, washed with benzene and dried. 1.6 g is obtained / 57.6 J $ 3 Athoxyearbonyl-6-methyl-9 / 4- (3-äthoxy.carbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro -4H-pyrido ^ T, 2-a7pyrimidin- -9-ylidene) -l, 3-dithiäthan-2-yliden7-4-oxo-6,7,8,9-tetrahydro- -4H-pyrido ^ T, 2- a7pyrimidine, which is converted from dimethylformamide

20 crystallizes and melts at 315 ~ 318 ° C. Analysis C ₂₆ H ₂₈ N ₄ O ₆ S ₂

calculated »C 56.10 H, H 5.07 #, N 10.07 < _f S 11.52 tf, found: 0 55.89 1> _% H 4.98 Ü _t N 10.20 #, S 10.80 $.

Example 5

To a mixture of 16.3 g of phosgene-N, N-dimethyl- -immonlum-chloride in 50 ml dichloromethane is stirred with stirring a solution of 23.6 g of 3- * ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9- -tetrahydro-4H-pyrido ^ I, 2-a7pyrimidine in 30 ml dichloromethane added dropwise and "the mixture is stirred for 3 hours. The solvent is distilled off and the residue is washed with ether crystallized .. 35 »2 g of strongly hygroscopic 3-Xthoxycarbonyl-6-methyl-9- / £ chlorine-N, N-dimethylammonio) -methylene / -

909828/0652

ORlGlNAt INSPECTED

is dried in vacuum. Analysis ^c ₁ 5 ^H 2O ^N 3 ° 3 ^C1 2

calculated: 01 _ionic : 19.6 i. found: Gl _ionic : 19.4 *. Beiapiel 6. ·

A solution of 1.8. g J-Xthoxycarbonyl-G-methyl-g-

- / ^ chlor-N, N-dimethyl-ammonio) -methylene / -4-oxo-6,7,8 _f 9-tetrahydro-4H-pyrido / 1,2-a7pyriniidin chloride and 5 mmol sodium acetate in 5 πα anhydrous' Ethanol is left to stand for 24 hours at room temperature and the precipitated sodium chloride is filtered and the filtrate is concentrated. The residue is dissolved in water and the pH of the solution is adjusted to 7 by adding sodium hydrocarbonate. The precipitated crystals are filtered, washed with water and dried. 0.92 g / 60 % / "3,9-dieth oxy carbonyl- 6-methy 1-4-oxo- -l, 6,7» 8-tetrahydro-4H-pyrido / T, 2-a7pyrimidine is obtained, · which melts at 138-14O ⁰ C.
Analysis C ₁₅ H ₂₀ N ₂ O ₅

calculated: 0 58.43 #, H 6.54 #, N 9.09 #, 20 found: C 58.65 #, H 6.53 $ »N 9.06 4>.

Example 7

A solution of 1.8 g, 3-3fthoxy carbonyl-6-methy 1-9- - / (chloro-N, N-dimethyl-amiiionio) -methylene 7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / 1,2-a7-pyrimidine chloride and 5 mmol sodium acetate in 5 ml anhydrous methanol is 24 hours at tree temperature left to stand and the precipitated sodium chloride is filtered and the filtrate is concentrated. The residue is dissolved in water and the pH of the solution is adjusted with sodium carbonate set to 7. The precipitated crystals are

30 den filtered, washed with water and dried. 0.96 g / S5 ij 3- · thoxycarbonyl-6-methyl-9-methoxycarbonyl-4-oxo-

is obtained

909828/0652

° fi! Q! NAL INSPECTED

which melts at 136-139 ° C. 28b A 1 13

Analysis C ₁₄ H ₁₈ N ₂ O ₅

calculated: O 57.14% H 6 * 17 ti _t -N 9.52 #, found: C 57.00 <&, H 6.25 #, N 9.52 1 °. .

5 Examples 8-13.

To the solution of 3.65 g of 3-ethoxycarbonyl-6-methoxy-9- / TChIOr-N, W-diinethylammonio) -methylene7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido / r, 2-a7pyrimidine chloride in 15 ml of anhydrous dichloroethane is added 0.02 mol of amine and the mixture is boiled for one hour. After cooling, the separated amine hydrochloride is filtered. The filtrate is concentrated. The oily, crystallizing residue is crystallized with * ether. The crystals obtained are filtered, washed with a''ther and dried. The product is recrystallized from anhydrous 'ethanol'. The products obtained and characteristic information can be found in Table 1.

909828/0652

ORIGINAL INSPECTED

Table 1 _#

For example Ami η
No.

product

Mp yield, ^0% C

Empirical Forrcal

Elemental analysis calculated found

C% H%

8. Aniline 3-thoxycarbony 1-5- 74 236 -

-raethyl-Q-CN-phenyl- decomposition

-N *, N'-dimethylformamidinium) -4-oxo- -1,6,7,8-tetrahydro d / Γ f

-4H-py rido / Γ, f pyrimidine-chloride

^C 21 ^H 27 ^N 4 ° 3 ^C1

60.30 60 * 08

6.45 6.54

13.40 13.42

9. 4-chlorine
-aniline

10. 4-methyl
-aniline

(O OO

• ο
ο »

3- <Vthoxycarbonil-6- 75 230 -methyl-9- (N) -4-decomposition

-chlor-phenyl-Ν ', Ν * - -dimethyl-formamidinium-4-oxo-l, 6,7,8- -tetrahydro-4H-pyrido- "" 2-a7py rimidine chloride

81 225 -226

^C 21 ^H 26 ^N 4 ° 3 ^C1 2

3- / ftoxycarbonil-6-

-methyl-9- (N) -4-

-methyl-phenyl-N *, N'-

-dimethyl-formamidini-

um-4-oxo-l, 6,7,8-tet-

rahy d ro-4H-py rido / T, 2-a7 ~ pyrimidine chloride

decomposition

^G 22 ^H 29 ^N 4 ° 3 ^C1

.60 54.95

51.10 60.83

5.74 5.73

6.70 6.81

12.35 12.26

12.92 12.79

cn
»Ο

OO

cn

Table 1 continued,

example
No.

Amine

Product Ausbsuta

Sch mp.

Empirical
formula

tlemantar analysis

calculated • found

> - / WC / MC

11 »

12th

X '
ITi

13th

4-methoxy- 3- * A * toxycarbonyl-6-

aniline -methyl-9-IN) -4-

-methoxy-phenyl-Ν ', Ν'-

-dimethyl-formamidini-

um-4-oxo-l _f 6,7,8-tet-

rahydro-4H-pyrido-

/ t, 2-Sj7py rim id in - =

-chloride

2-naphthyl- 3- "£ thoxycarbonyl" 5-

amine-methyl-9- (N) -2-naphthyl-

-N *, N'-dimethyl-forraamidinium-4-oxo-l, 6,7,8- -t, 3t rahy dro-4H-py rido- "", 2-a7 pyrimidine chloride

2-methoxy- 3- ^e ethoxycarbonil-6-

carbonyl aniline

yy -carbonil-phenyl-N ', N * - -dimethyl-formaraidiniumlh

CO OO to OO

cn to

xjejjStetrahydro -4H-pyrido / T, 2-a7pyrimidine · -chloride - 224 CH NO Cl
Decomposition 22 29 4 4

- 235 C ₂₅ H ₂₉ N ₄ O ₃ Cl

- 211 C _{? 3} H
Decomposition **

53.95
53., 58

64.10
53.69

5 »47
6.65

6.19
6.17

57 .31 5 , 09 11 .75 57 .33 5 , 09 11 .75

Example 14.

To an aqueous solution of 4.2 g of 3- * A * thoxycarbo-

nyl-6-ynethyl-9-CN-phenyl-N ', N ^> -ciimGthyl-formamidiniuin) ~ 4-

a 20 W / V $> potassium carbonate solution is given. The precipitated crystals are filtered, washed with water and dried. 3> 4 g / B9 ij 3-'A * thoxycarbonyl-6-methyl-9- (li-phenyl-N », N-dimethylformamidino) -4-oxo-l, 6,7,8- -tetrahydro-4H-pyrido _i / r, 2-a7pyriii; idin, which is also Umkriotalli

10 sieren from 'ethanol at 193-195 ⁰ C melts. Analysis ^c ₂ i ^H 26 ^N 4 ° 3 calculated: C 65.98 $, H 6.81 '/>, B 14.65 Sb, found: C 65.89 S ", H 6.79 ti, N 14.69 ^.

Example 15.

15 To a mixture of 22.1 g of phosgene-N-methyl-N-

-phenyl-iffinonium -chlorid in 50 ml Dichlormethaa is a solution of 23.6 g 3- "A" thoxy carbonyl-6 ~ me thy 1-4-0X0-6., 7,8,9-tetrahydro-4H -pyrido _i / l, 2-a7pyrimidin in 30 ml of dichloromethane is added dropwise and the reaction mixture is boiled for 3 hours. After the mixture has been distilled off, the residue is crystallized with ether. 41.2 g of strongly hygroscopic 3- - * ethoxycarbonyl-6-methyl-9 - / (chloro-N-methyl-K-phenyl-ammonio) -methylene7 are obtained -4-oxo-6,7,8,9-tetrahydro-4H-pyriäo / T, 2-a7pyΓimidine chloride which is dried in vacuo.

25 Analysis C ₂₀ H ₂₅ N ₅ O ₅ Cl ₂

calculated: Cl _ionic : 8.36 * found: Cl _ionic : 8, ^ 5 *

Example 16.

For the solution of 3-'A'thoxy carbonyl- 6- methyl 1-9- -N-methyl-K-phenyl-ammonio) -methylene7-4-oxo- 6,7,8,9-tetrahydro-4H- pyridO2 ^ L, 2-a7pyi ^> iB ^lidia - ^{cnlorid in 20} ^ ¹¹ anhydrous dichloromethane: 0.2 ml of aniline is added and the reaction mixture is boiled for 1 hour. After cooling down, the

909828/0652

ORIGlNAt. INSPECTED

2854119

Divorced Anllin-HydrοChlorid filtered. The mother liquor containing dichloromethane is concentrated. The residue is crystallized with Vither. The precipitated crystals are filtered off, washed with 'A'ther and dried. 25.9 g / 54 ^e ^ -A'thoxycarbonyl-e-methyl-g- -CN ', ^ -diphenyl-N-methylformamidinium) -4-oxo-1,6,7,8-tetrahydro are obtained -4H-pyrido / I, 2-chloro-aypyrimidin id, which melts after recrystallization from "A'thanol with decomposition at 186-188 ⁰ C.

10 Analysis C ₂₆ H ₂₉ N ₄ O ₅ Cl

calculated: C 64.95 %, H 6.Ο4 6, N 11.66 $ _f found: C 64.76 5ö, H 6.09%, N 11.26 #.

Example 17.

For the aqueous solution of 24 g of 3-xthoxycarbonyl-6-methyl-9- (N, W ^> -diphenyl-N-methyl-formamidinium) -4-oxo-1 _f 6,7,8- -tetrahydro-4H-pyrido _<< / r, 2-a7pyridinium chloride is given a 20 W / V ia potassium carbonate solution. The precipitated crystals are filtered, washed with water and dried. 16.7 g / 75 v £ 7 3-A * thoxycarbonyl-6-methyl-9- (N, K »-diphenyl-U-methylformamidino) -4-oxo-l, 6,7,8 are obtained tetrahydro-4H-pyrido / X, 2-a7pyrimidin, which after recrystallization from 'ethanol at 199 - 202 ⁰ C melts. Analysis C ₂ 6 ^H 28 ^N 4 ° 3
calculated: C 70.25% H 6.31 #, N 12.61 £,

25 found: C 69.97 #, H 6.27 *, N- 12.42 tf.

Example 18.

For the solution of 21 g of 3- * A "thoxycarbonyl-6-methyl-9- - / ^ chloro-K-methyl-N-phenyl-ammonio) -methylene7-4-oxo-6,7,8,9- -tetrahydro -.4H-pyrido ^ :, 2-a7pyrimidin chloride in 20 ml water-free dichloromethane 0.2 mol of 4-chloroaniline is added urtä is boiled for one hour the reaction mixture. After cooling, the precipitated 4-chloro-aniline hydrochloride is filtered.

909828/0652

2 β C ₅ λ 113

The dichloromethane-containing cutter liquor is concentrated. The 3-ethoxycarbonyl-6-methyl-9- / CT- (4-chloro-phenyl) -li ^> -phenyl-li ^t -methylformamidiniuin7-4-oxo-l, 6.7 _f 8- tetrahydro -4H-pyridoZl, 2-a7pyrimidine chloride is dissolved in the water and a 20 w / vg potassium carbonate solution is added to the solution. The precipitated crystals are filtered, washed with water and dried. 13.3 g / 55.5 °] of 3-ethoxycarbonyl-6-methyl-9- / N- (4-chlorophenyl) -N ^f - -phenyl-N ^f -methylformamidineq / -4-oxo-1 are obtained, 6,7,8-tetrahydro-4H- -pyrido ^^^ - e / pyrimidine, which melts at 194 - 196 ⁰ C after recrystallization from ethanol.
Analysis C ₂₆ H ₂₇ NO ₅ Cl

calculated: C 65.15 # _t H 5.65 9S ₁ N 11.71 $>, found: C 64.85 # _t H 5.83 #, ΪΓ 11.66 Ii.

15 Example 19.

For the solution of 21 g 3-2Üthoxycarbonyl ~ 6-methyl-9- - / Cchlor-N-methyl-N-phenyl-ammonio) -methylene7-4-oxo-6,7,8,9- -tetrahydro-4H- pyrido / r, 2-a7pyrimidine chloride in anhydrous dichloromethane is added to 0.2 mol of 4-methyl-1-aniline and the reaction mixture is boiled for 1 hour. After cooling, the 4 ^{l /} l ethyl aniline hydrochloride which has separated out is filtered off. The dichloromethane filtrate is concentrated. D _a ^# s obtained 3- -2L thoxycarbonyl-6-methyl-9 - /? - (4-methyl-phenyl) -N'-phenyl-N ^f - methyl-formamidinium / -4-oxo-l, 6, 7,8-tetrahydro-4H-pyrido- / Ϊ, 2-a7pyrimidine chloride is dissolved in water. A 20% potassium carbonate solution is added to the aqueous solution. The precipitated crystals are dissolved, washed with water and dried. This gives 14.7 g / 64 * A * U 3 thoxycarbonyl- -6-methyl-9-Z '- (4-methyl-phenyl) -li ^l -phenyl-N "-methyl-f ormamidinq7-4-oxo -l, 6,7, e-tetrahydro ^ H-pyrido / T, 2-a7pyrimidine, the product melts at 161-163 ⁰ C after recrystallization from 'ethanol.

909828/0652

Analysis C ₂₇ H ₅₀ N ₄ O ₅

calculated: C 70.75 # _f H 6.56 #, N 12.21 #, 'found: C 70.55%, H 6.62 4>, N 11.91 <&.

Examples 20-23.

In the solution of 0.05 mol of pyrido / 1,2-a7p.yrimidine The starting material in Di chlorine than is 0.055 mol of isocyanate Added dropwise at room temperature. The reaction mixture is boiled for 10 hours and left to stand at room temperature for 2 days the solvent is distilled off. The residue is crystallized from ethanol. The compounds produced are listed in Table 2.

909828/0652

Table 2.

2990/838606

Example starting material no.

Isocyanate

product

ÄU3-

beuta

C /

/O

Schmp,
⁰ C

Empirical formula

":. · 3ηΐ3Γ analysis ö arsenic? 31 ge for. ds η

22nd

23

20. S-Älhoxycarbonyl-e-phenyl- -methy1-4-0X0-6,7,8,9- -iso- -tetrahydro ^ H-pyridocyanate T 2-e7pyrimidine

chloroacetyl isocyanate

tooyl-

iso-

cyanate

21 «3-ethoxycarbonyl -e-methyl ^ -oxo- -6,7,8,9-tetrahydro d ^ T7

py pyriraidin

3-A \ hoxycarbonyl- -S-methyl ^ -oxo- -6,7,8,9-tetrahydro -4H-py rido ^ T, 2-a7-pyrimidine ""

3-Anino-carbonyl- -e-roethyl ^ -oxo- -6,7,8,9-tetrahydro-4H-pyrido / T, 2-pyrimid in

tosyl

ioo-

cyanate 3-'A * choxycarbonyl- 46 2CO-2O1 G ₁ -6-rnethyl "9- (N- -

-phenyl-amino- carbonyl) -4-oxo- -1,6,7,8-tetrahd ro-4H-pyrido _t 2-a7py riraidin

3- ^ Aloxycarbonyl- 74 158-160
hl ^ hl

acetyl-aminocarbonyl) -4-oxo-l, 6, 7,8-tetrahydro- -4H-pyride o ££, 2-a7 ~ pyrimidine

3- ^ tho> ycarbonyl- 80 182-183 hlC

zylamino-carbonyl) -4-oxo-l, 6,7,8- -teteahydro ^ H-pyrido ^ T, 2-7U

SZtTosylaminocar bonyl) aminocarbonil 7-6-methyl-9- 49 -Ctozylaminocarbo-

nil) -4j-oxo-l _Ä 6,7,8- -fetrahyaro-4H * *

-py rido / T, 2-a7 « py rimidin

164

C _{1 (} -H _1i3 N η Cl 15 18 3 5

^C 26 ^H 27 ^N 5 ° 8 ^S 2

64.21 5.95 11.83 63.95 5, Eq 11.55

50.63 5.06 11.30 51.02 .5.02 11.63

55.42 55.92

5.35

5 * 30

51.90 4.52 11.64 52.28 4.48 11.51

2.1 moles of isocyanate are used for 1 mole of starting material.

_ oar -

Examples 24-28.

A mixture of 23.6 g of 3-A * thoxycarbonyl-6-methyl-4-oxo-4H-pyrido / T, 2-a7-pyrimidine and 0.1 mol of isocyanate is stirred for 72 hours at 40-50 hours. The thick viscous reaction mixture formed is suspended in 200 ml of ethanol, filtered and washed with ethanol. / If the reaction using n-butyl isocyanate is carried out, is carried out at 80-100 ⁰ C. /

The compounds produced are shown in the table

10 enumerated.

909828/0652

3390/828606

Tabel

Example isocyanate no.

product

Empirical

Yield m.p. C formula
%

elementary analysis barschnet found

C %%

24. n-butyl isocyanate

25 · phenyl isocyanate

26. 4-chloro-phenyl isocyanate

27. 3-chloro-phenyl- -ioocyanate

S-iethoxycarbonyl-e-methyl-

-9 - / "Cn -butylamino) -carbo- 35 152-155

ny17-4-oxo-l, 6,7,8-tetra-

hyddo-4H-py rido / I, 2-a7 «

pyrimidine

3 - /? Thoxycarbonyl-6-methyl-

-9- ^ phenyl-aminay-carbo- 74 198-200

nil / -4-oxoal, 6,8,9-tetrahydro-4H- d ^ I pyrimidine

S-ethoxycarbonyl-e-methyl-

-9 - / (4-chloro-phenyl-ai!) Ino) - 82 206-210

-carbony17-4-oxo-l, 6,7,8- -tetrahydro-4H-pyrido- / Ί, 2-a / pyrimidine

3-ethoxycarbonyl-6-methyl-

-9- / i3-chloro-phenyl-amino) - 78 194-198 b

-carbonyl / M-oxo-l ^^. S- -t et rahyd * ro-4H-py rido ^ T, 2-a / pyrimidine ^C 17 ^H 25 ^N 3 ° 4

^C 19 ^H 21 ^N 3 ° 4

60.90 7.47 12.52

60.25 7.41 12.40

No melting point depression with the product of example 20.

^C 19 ^H 20 ^N 3 ° 4 ^C1

^C 19 ^H 20 ^N 3 ° 4 ^C1

58.50 58.10

58.50 58.21

5.13 5.07

5.13 5.05

10.78 10.59

10.78 10.61

28. 3,4-dichloro-phenyl- isocyanate

3-Ai: hoxycarbonyl-6-methylg ^ S ^ dihlhl

^^ chorphenyl -amino) -carbonyl / -4 · οχο- -1,6,7,8-tetrahydΓ0-4Η- -py rido ^ T, 2-a / py rimidin

79

208-212 ^C 19 ^H 19 ^N 3 ° 4 ^C1 2

53.80
53.28

4.48
4.40

9.90 9., 3

2 8 S A 113

Example 29.

A solution of 1.8 g of 3-'AT; hoxycarbonyl-6-methyl-S- - / Cchlor-N, N-diDieth.yl8immonio) -methylene7-4 ~ oxo-6,7 _> 8,9-tetrahydro-4H -pyriao ^ L, 2-a7pyrimidine chloride in 5 ml of ethanol is boiled for 30 minutes. After cooling, the precipitated crystals are filtered, washed with ethanol and dried. Ivan receives 1.08 g / I3 ti? 3-'A'thoxycarbonyl-6-methyl-9- (^, K-diniethylamino-carbonyl) '- 4-oxo-6,7,8,9-tetrahyano-4H-- -pyrido / I ^ -a / pyrimiäin-hydrochloriä, which, after recrystallization from ethanol, melts at 166-168 ° C. with decomposition. Analysis ^G i5 ^H 22 ⁱⁱ 3 ⁰ 4 ^G1

calculated: C 52.40> £, H 6.45 *, W 12.22 <·, Cl 10.31 1 » found: C 52.18 g, H 6.58 %, N 12.30 <?>, Cl 10.45 i *

Example 30.

3.26 g of 3- * A * thoxycarbonyl-6-methyl-9- (methyltio-thiocarbonyl) -4-oxo-l, 6,7 »8-tetrahydro-4H-pyrido2T, 2-a7pyrimidine ₍ and 0.6 g 'ethylenediamine are boiled for 10 hours in 50 ml Eenzol. After cooling, the precipitated yellow crystals are filtered, covered with benzene and dried to i'.ian 1.9 g / u> 2 ij 3-üSthoxycarbonyl-6-methyl-9- (2-imidazolides) -4-oxo-6,7, ü _t 9-tetrahydro-pyrido 4K / r, 2-a7pyriiaidin, which after recrystallization from i 'in; ethylformamidin at 252 - 254 ⁰ C melts.
Analysis C ₁₅ H ₁₈ M ₄ O ₅

25 calculated: C 59.15 #, H 5.90 $, N 18.40? Έ, found: C 58.91 #> H 5.85 U ₉ U 18.35 $

Example 31

ivian dissolves 1.0 g of 3- * A * thoxycarbonyl-6-methyl-9- (2- -imidazoliden) -4-oxo-6,7,8, S-tetrahydro-4H-pyrido ^ :, 2-a7-pyriinidine in 10 ml of ethanol. The solution is made with hydrogen

chloride gas saturated and concentrated. The residue becomes out • Recrystallized from a mixture of 'ether and' ethanol. Man

909828/0652

receives 0.9 g of 3-thoxycarbonyl-6-methyl-9- (2-imidazoliden) -4-0X0-6,7, S, 9-tetrahydro-4H-pyrido ^ T, 2-a7pyrimidine bis- hydrochloride, which melts at 19O ^{0 C with decomposition.} Analysis ^G i ₅ ^H ₂ 0 ^I ' ⁱ 4 ⁰ 3 ^C1 2

5 calculated: C 59.15 £, H 5.90 #, N 10.40 #, found: 0 58.91 #, H 5.85%, N 18.35 #.

Example 32.

lian stirs 3.6 g of 3-'Athoxycartonyl-6-methyl-9 _: / 'Cchlor- -K, K-dimethylammonio) methylene / -4-0X0-6,7,8,9-tetrahydro-4H- -pyrido _J / r ^{2-r-pyrimidine} a7P3 chloride and 1.2 g 'A'thylendiamin in 40 ml of dimethylformamide at 40 ⁰ C and after cooling the precipitated crystals are filtered, ater with "washed, dried. 1.0 g of 3-ethoxycarbonyl-6-methyl-9- (2- -iir, idazoliden) -4-oxo-6,7,8,9-tetrahydro-4H-pyrido / T, 2-a7- are obtained

15 pyrimidin which at 252 - 254 ⁰ C melts.

Example 33

A mixture of 2.0 g of 3-amino-carbonyl-2,6-dimethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido _i / l, 2-a7pyrimiäin and 2.2 g of phenyl isocyanate is heated to 80 ⁰ C and the resulting solution is stirred at 50-6O ⁰ C. After cooling, the reaction mixture is treated with 30 μl of ether, the precipitated crystals are dissolved in ethanol, filtered and the filtrate is allowed to crystallize in the refrigerator and the precipitated crystals are filtered and washed with ethanol. 1.4 g of 3-aminocarbonyl are obtained -9- (phenyl-amino- carbonyl) -2,6-dimethyl-4-oxo-l, 6,7,8-tetrahydro-4H-pyrido- ^ / X, 2-a7pyrimidine _f Melting point: 187-1 " 88 ⁰ C. Analysis C ₁₈ H ₂₀ N ₄ O ₃

calculated: C 63.51 ¹ ^, H 5.92 #, N 16.46 *, 30 found: C 63.49 i, H 6.00 4, Ν 16.26 #.

909828/0652

Example 34.

1.6 g of potassium hydroxide are dissolved in 20 ml of ethanol. An ethanolic solution of 3.6 g of 3-ethoxycarbonyl-9- (phenyl-aminocarbonyl) -6-methy 1-4-oxo is added to the ethanolic solution of potassium hydroxide -1,6,7,8-tetrahydro-4H-pyrido - "/ T, 2 ~ a7pyrimidine given -" The reaction mixture is boiled for 50 hours and the crystals which separate out after cooling are filtered, washed with chloroform and dried. 5.1 g of potassium 9- (phenylamino-carbonyl) -6-methyl-4-oxo-1,6,7,8-tetrahydro-4H-pyrido / r, 2-a7pyrimidine-3-carboxylate, which is obtained in 276-280 ⁰ C melts with decomposition.

Analysis C ₁₇₅₄

Calculated: C 55.88 f6, H 4.41 1 », N 11 * 50 <fo _f found: C 56.02 7 °, H 4 * 50 %, N 11.42 #.

15 Example 35.

3.1 g of potassium 9- (phenylamino-carbonyl) -6- methyl ~ 4 ~ oxo-1,6,7,8-tetrahydro-4H-pyrido / T, 2-a7pyrimidine- -5-carboxylate are dissolved in 250 ml of water with heating. The pH of the solution at 40 - 50 ⁰ C set at 38 W / V $ hydrochloric acid solution to 1. The crystals which have separated out are filtered off, washed with water and dried. 2.2 g of crystals are obtained, which are crystallized from acetonitrile. 9- (Phenyl-aminocarbonyl) -3-carboxy-6-methyl- -4-oxo-l, 6,7,8-tetrahydro-4H-pyrido / r, 2-a7pyrimidine with a

25 ner yield of 25 #
Analysis ^ γΗχγ ^ Οφ

calculated: C 62.37 ^a / °, H 5.24%, N 12.84 #, found: C 62.18 $, H 5.18 &, N 12.45 3 $.

Example 36.
2 g of 6- ^ ethyl-4-oxo-6,7,8,9-tetrahydro- -4H-pyrido ^ r, 2-ajpyrimidine with phosgene-N ^ -dimethyl-immonium- chloride on the · in example 5. specified way around. You get

909828/0652

such a strongly hygroscopic 6-methyl-9 / chloro-N, N-dime ethyl-ammonio) -niQthylene / -4-oxo-6,7,8,9-tetrahydro-4H- -pyrido ^ I ^ - ^ pyrimidine chloride, which is dried in vacuo will.

Analysis ^σ ι ₂ ^Η ΐ7 ^ίΙ 3 ⁰⁰¹ 2

calculated: Cl _ioniach : I ₂ .22 f> found: Cl _ioniach : 12.10 *

Example 37.

Heat 6- & ethy 1-9 - ^ - ChIOr-N, N-dimethylammonio) -methylene / -4-oxo-6,7,8,9-tetrahydro-4H-pyrido ^ T _f 2-a / ⁷ -pyrimidine -chloride in ethanol 30 minutes. The reaction mixture is concentrated and the 6-kethyl-9- (N _f JT-dimethylamino-carbonyl) -4-0x0-6,7,8,9-tetrahydr0-4H-pyrido- ^ / T, 2-a7pyrimidine hydrochloride obtained is usually run over into a base. Me base is crystallized from petroleum ether.

6-iiethyl-9 "2iii, N-dimethylan! Ino) carbonyl / -4-oxo- -1, 6,7,8-tetrahydro-4H-pyrido ^, 2-a7-pyrimidine.

Analysis ^c i2 ^H 17 ^N 3 ° 2

calculated: C 61.26 <&, H 7.28 U ₉ S 17.86 νί, found: C 61.40 #, H 7.11 4> _t N 17.69 ^.

20 Example 38.

3-Cyano-6-methyl-4-oxo-6,7,8,9-tetrabydro -4H-pyrido ^ T, 2-a7pyrimidine - as indicated in Example 5 with phosgene-NjN-dimethyl-immonium chloride . Strongly hygroscopic 3-cyano-6-methy 1-9- / C chloro-Ii, N-dimethyl-ammonio) -methylene / -4-oxo-6,7,8,9-tetrahydro-4H-pyrido- / Xt 2-a7 pyrimidine chloride.
Analysis C ₁₃ H ₁₆ N ₄ ⁰⁰ I ₂
Calculated: Cl _ionic : 10.70 ^: / - found: Cl _ionic : 10.52 %.

Example 39.
_{Treats 3-cyano-6-methyl-9ä / /} (chlor-N,li-dimetnyl-ammonio)-metnylen7-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-

as indicated in example 29.

909828/0652

The ethanolic solution is concentrated and the residue is crystallized from ethyl acetate. 3-Cyano- -6-methyl-9- (W, N-dimethylamino-carbonyl) -4-oxo-l, 6,7,8- tetrahydro - ^ - pyrido / r ^ -a / pyrimidine, yield : 60% analysis ^G.

calculated: C 59.98 #, H 6.20 #, N 21.51 #, found: C 59.90 #, H 6.11 #, N 21.22 #.

Example 40.

3.4 g of 3- * ethoxy car bony 1-6-methy 1-9- (N, ΝΙΟ -dime thylamino-carbonyl) -4-oxo-6,7,8,9-tetrahydro-4H- are dissolved pyrido-Zl »2-a7pyrimidine hydrochloride in 20 ml of water and the solution • is neutralized with a 5 W / V # sodium bicarbonate solution. The reaction mixture is extracted with chloroform. The chloroform solution is dried over sodium sulfate, filtered and concentrated. The residue is recrystallized from a mixture of ethanol and water. 2.1 g of 3-ethoxycarbonyl-6-methyl-9- (li, N-dimethylamino-carbonyl) -4- -oxo-l, 6,7,8-tetrahydro-4H-pyrido _i / r, 2- a7 pyrimidine. Analysis ⁰ ι ₅ ^Η ₂₁ ^Ν 3 ° 4

20 calculated: C 58.60 #, H 6.90 4>, N 13.66 #, found: C 58.25 4, H 6.94 #, N 13.56 <&.

Example 41 «

3.07 g of 3-ethoxycarbonyl-6-methy 1-9- (N, N- -dimethylamino-carbonyl) -4-oxo-1,6,7,8-tetrahydro-4H-pyrido- / T are dissolved , 2-a7pyrimidin solution ² obtained in Ur ^# A'thanol · are added to a 20 W / V $> solution of ammonia and the reaction mixture for 3 days in a closed vessel left. The precipitated crystals are filtered off and washed with ethanol. 1.18 g of 3-aminocarbonyl-6-methyl-9- - (N, N-dimethylamino-carbonyl) -4-oxo-l, 6,7,8-tetrahydro-4H- are obtained

-pyrido ^ T, 2-a7pyrimidine, melting point: 220 ⁰ C.

909828/0652

285-11

Analysis C ₁₅ H ₁₈ N ₄ O

calculated: G 56.09 H ₉ H 6.53 #, N 20.12 #, found: C 55.89 tf _# H 6.52 #, N 20.33 K>

Example 42.

3,6-diethoxycarbonyl-6-methyl-4-oxo-1,6,7, e-tetrahydro- ^ H-pyridine ^ / T, 2-a7pyrimidine according to Example 41 is treated with ammonia in ethanol. This gives 1.51 g of 3-aminocarbonyl-9-ethoxycarbonyl-6-methyl-4-oxo-1,6,7,8 "-tetrahydro ^ H-pyrido / T ^ -a / pyrimidine, which at 251 ⁰ C melts.

Analysis β ^, Ι ^ γΝ-Ο *

calculated: C 57.12 g, H 6.28 tf, N 15.30 tf found: C 56.98 #, H 6.12 tf, N 15.50 £.

Example 43

15 Dissolve 0.416 g of 3- * A * thoxycarbonyl-4-oxo-4,6,7f8-

- te trahy droopy rrolo ^ T, 2-g7pyrimidine in 4 ml of benzene land to the solution add 0.24 g of phenyl isocyanate. ^ & a reaction mixture is left to stand for 5 days at room temperature and the precipitated crystal is filtered and washed with Ben

20 zoles of washed M <m Q & hßlt O ₉ g © g / f6o5 ^ J 3- ^# ethoxycarbonyl

£ ₉ / ρ ^ eJhiGS melts at 240-241 ⁰ C.

Analysis: O ^ ™! ^ ™! ^ © «

calculated: G 62.38 ^ ₉ H 5.23 *, N 12.84 4>, found: C 62.51 $ »H 5.15 1> _% N 12.90 g.

Example 44 *

Is added dropwise to the solution of 0.8 g of _{3-cyano-4-oxo-7,8-f} -4.6 tetraliydr © -pyrrolo / r, 2-a7pyrimidin and 0.6 ml of carbon disulfide in 10 ml ethanol a Löstsng of 0 , 6 g potassium hydroxide 30 in 10 ml 'athaaol. The reaction mixture is stirred for 1 hour at room temperature and concentrated under reduced pressure. One obtains a dipotassium salt of 3-cyano-9- / XBIS-t ⁱ iolat) -

909828/0652

methylene / «4 ~ oxo-4, f>, 7> 8-tetrahydro-pyrrolo /, 2-a7pyriraidine.

Example 45.

A dipotassium Sal ζ of the cyano-9- / £ bis-thiolate) - methylene / -4-oxo ~ 4,6,7 »8-tetrahydro-pyrrolo / 1,2-a7pyrimi ~ DinB - prepared as in Example 44 - Is dissolved in 20 ml of ethanol and 1.25 g of dimethyl sulfate are added to the solution and the reaction mixture is stirred for 1 hour at 40 G. The crystals which separate out are filtered off and washed with ethanol. This gives 0.46 g / 36.5 ¹ ^ / 3-cyano-9 ~ - (methylthio-thiocarbonyl) -4-0x0-1,4,6,7rtetrahydro-pyrrolo-ZI, 2 ~ a7pyrimidine, which at 202 - 203 ⁰ C melts. Analysis C ₁₀ H ₉ N ₅ OS ₃ .

calculated: C 47.79 #, H 3.61 #, N 16.72 H ₉ found: C 48.01 H ₉ H 3.52 #, N 16.81 Ά.

909828/0652

Claims (2)

Claims
1. Compounds of the general formula I ¹⁰ O optically active .Antipode and salts thereof, wherein R represents hydrogen or C _1-4 alkyl, E 'represents hydrogen or C _1-4 alkyl, R and R' together form a group of the formula - / CH = CH /, -, which are attached to the two adjacent Hing- -Bond carbon atoms, the dashed line stands for a hyphen, R ² denotes hydrogen or alkyl with 1-4 carbon atoms, S? Hydrogen, alkyl with 1-4 carbon atoms, Phenyl, carboxy, or its alkali metal salt, A Ik oxy carbonyl with 1-4 carbon atoms in the alkyl part, carbamoyl, cyano, -CONH-CO-NH-SO ₂ -C ₆ H ₄ -Ch ₅ or - / CH ^ / -COOR ¹ ^ "means, where s« 1-3 and ß ¹⁴ for hydrogen or alkyl with 1-4 carbons material atoms stands,
and
η = O or 1, 809828/0652 a / when R ° is hydrogen and H ¹² and H ¹¹ η ιλ and RP and R together form a hyphen, Ϊ stands for an oxygen or sulfur atom deprived of its outer electron pair, and in this case R and R ⁸ mean a lone pair of electrons or Y stands for one who has been robbed of its outer pair of electrons Nitrogen atom, R ⁷ denotes alkyl with 1-4 carbon atoms, optionally substituted .Aryl with 6-10 carbon atoms, or aralkyl with 7-12 carbon atoms, R denotes a lone pair of electrons or C 1-4 alkyl and in the latter case a halide ion forms a salt with the positive nitrogen atom, X / R ⁴ , R ^ R ⁶ J means halogen or X stands for an oxygen or sulfur atom deprived of its outer electron pair, R means hydrogen or G _{1 A} alkyl, R- ^ and R mean a lone pair of electron pairs or X stands for a nitrogen atom deprived of its outer electron pair, R ^ means chloroacetyl, alkyl with 1-4 carbon atoms, optionally substituted ArIy having 6-10 carbon atoms, or an optionally substituted heteroaryl, R ^ represents hydrogen or alkyl and R represents a lone pair of electrons or b / if R ¹² and R ^{15 form} a hyphen and R is hydrogen and R ^ and R together form a hyphen, then the definition of R ⁴ , R ⁵ , R ⁶ , fi ⁷ , H ⁸ , * and Y is as given in point a /, and 909828/0652 c / if H ¹⁰ and H ¹¹ and R ^1Z and R ¹³ together each form a hyphen, then Ϊ means an oxygen or sulfur atom deprived of its external pair of electrons, and if R, R and -R? a lone pair of electrons, then a positive cation forms a salt with the so geoildefcen anion, or and R ^y denotes a lone pair of electrons, R ' denotes hydrogen or alkyl with 1-4 carbon atoms or Ϊ means one deprived of its outer pair of celabs Nitrogen atom, R? means hydrogen, alkyl with 1-4 carbon atoms, optionally substituted aryl with 6-10 carbon atoms, R stands for alkyl with 1-4 carbon atoms and R- * means a lone pair of electrons, K ⁶ , r7j stands for halogen, or X stands for one deprived of its outer pair of electrons Oxygen or sulfur atom, and if R ^, R- ^ and R is a lone pair of electrons, forms a positive cation with the anion thus formed is a salt, or R ^ means hydrogen or alkyl of 1-4 carbons material atoms,
R ^ and R ⁶ stand for a lonely pair of electrons or X stands for a pair of regrets that has been regretted by its outer pair Nitrogen atom, and R ⁴ stands for Ohloroacetyl, alkyl with 1-4 carbon atoms, or optionally substituted 909828/0652 285A113 tes aryl with 6-10 carbon atoms or optionally substituted heteroaryl, H ^ is hydrogen or alkyl _with 1-4 Carbon atoms and
5 R stands for a lonely pair of celabs, and if I and X for one of its outer electron pair deprived oxygen or sulfur atom, and K ^, R, R, R and R / mean a lone pair of electrons or Y and Ji for one of their outer pair of electrons tes nitrogen and R and R ^y mean a lone pair of electrons and Br and R stand for hydrogen or Alley 1 with 1-4 carbon atoms, then R and R ^{ together form an optionally substituted -ZCH ₂ / - ,. where s = 1, 2, 5 or 4. 2. Compounds of general formula I according to claim 1, wherein η «1 is. 3. Compounds of general formula I according to claim 1, characterized in that R and K ^{1 represent} hydrogen. 4. Compounds of general formula I according to claim 1, characterized in that H for hydrogen and R ¹ for alkyl nit 1-4 carbon atoms 25 men, preferably methyl. 5. Compounds of general formula I according to claims 1-4, characterized in that R ^{5 represents} carboxyl, methoxycarbonyl, 'ethoxycarbonyl or Carbamcyl stands.
30 6. Process for making the compounds of the general formula I. 909828/0652 optically active antipode, and salts of the same, “by g k β η η ζ e i c h η θ t that one a combination of the general formula II II 12 3
where £, ß, H, H, 0 and η are as given above, a, / with a di-halogen-methylene-ammonium-halide der general formula III ; ν = c; • St. HIg- III where HIg stands for halogen ß ¹ ^ for AIiQ / 1 with 1-4 carbon atoms, or optionally substituted aryl with 6-10 carbon atoms, ü ^{16 means} alkyl with 1-4 carbon atoms or A means an anion, 909828/0652 28B4113 and thereby a connection · of the general formula Ia wherein R, R ¹ , R ^, R ³ , R ¹⁵ , R ¹⁶ , A, η and the dashed line are as indicated above - obtained, or
3p / with a carbon disulfide of the formula IV CS ₄ , IV preferably implemented in the presence of alkali ions and thereby a compound of the general formula Ib 12 3
wherein R, H, R, R, n, HIg and the dashed line are as indicated above - and M means an alkali ion - is obtained, or
a -, / with an isocyanate of the general formula V ³⁰ H ¹⁷ -N 909828/0652 - where R ^{7 is} alkyl with 1-4 carbon atoms, chloroacetyl, optionally substituted aryl with 6-10 carbon atoms or optionally substituted heteroaryl, and V is oxygen or sulfur atom and thereby compounds of the general formula Ic ■ rfjrfV τ obtained, wherein R, R ¹ , R ² , R, R ¹⁷ , V, η and the dashed 15th line as indicated above - and if desired, the compound of the general formula Ia, Ib or Ic obtained by one of the above methods is converted into another compound of the general formula Ia, Ib, Ic or I and, if desired, in a compound of the general formula I obtained, a substituent R ² , R V- ^, R ^, R ⁶ , R ⁷ , R ⁶ , R ⁹ , R ¹⁰ , 11 Ί? 13 en 2 E ₁ R, R, X or Ϊ in another substituent R, _K 5, fl \ * 5, H ⁶ , J ?. H ⁸ , H ⁹ , H ¹⁰ , JJ ¹¹ , K ¹² , E ¹ 'converted in any order and / or converted into a pharmaceutically suitable salt or released from its salt and / or, if desired, a racemate of the general formula I resolved. 7. The method according to claim 6, characterized in that in the process variant a · ^ / dihalo-methylene-ammonium halide of the general formula III - wherein R ¹ ^, R, HIg and A are as indicated in claim 6 - with a compound of the general formula II 909828/0652 worm R ₁ R, R, R, η and the dashed line are as indicated in claim 1. - Reacts in the presence of an inert solvent. 8. The method according to any one of claims 6-7, characterized in that. that one driving variant aj / at 0 - 180 ⁰ C carries out. 9. The method according to claim 6, characterized in that in the process variant a ~ / carbon disulfide of the formula IV with a compound of the general formula II - in which R, R ¹ , R ² , R ⁵ , n. _and the dashed line are as indicated in claim 1 - is reacted in the presence of an alkali cation in a lower alcohol. 10. The method according to claim 9s characterized by g e, that process variant a ~ / at 0 - 120 ⁰ G. 11. The method according to claim 6, characterized in that when carrying out process variant a, / an isocyanate of the general formula 17 ·
mel V - in which R ' and V are as indicated in claim 6 with a compound of the general formula II - in which R, JR, R, R * and η and the dashed line are indicated in the claim - in the presence of a Lewis acid or Base at O - 250 ⁰ C carries out. 25 12. The method according to any one of claims 6 and 10-11, characterized in that a compound of the general formula I - in which β, R , R ² , R ^, η and the dashed line are as indicated above - and R ¹⁰ and R ¹¹ , and R ² and R ⁵ together one 30 form a hyphen, X and Ϊ represent a sulfur atom, and fi ⁴ , R ^, R ⁶ , R ^, R ⁸ » ^ Qi ⁿ mean solitary electron pair, and an alkali cation with the dianion forming it 909828/0652 ⁶ 285-113 o forms in salt - alkylated and receives such a compound of the general formula I, in which R, R ¹ , R ² , κ ⁵ , η and the dashed line are as indicated in claim 1, R ⁹ and H ¹⁰ and R ¹¹ and R ¹² together form a connective b dash, K stand for ¹⁵ hydrogen, X and Y represents a sulfur atom, R, R, K ', R representing a lone ülektronenpaar, R ⁴ is alkyl having 1-4 carbon atoms. 13. The method according to claim 6 and according to any one of claims 11-12, characterized in that that a compound of the general formula I - wherein 12 3
R, R , R, R, η and the dashed line as in the claim 1. are given, R ^ü and R and β ² and H * together form a hyphen, X and Y denote a sulfur atom and R ⁴ , R ⁵ , R ⁶ , fi ", H and R ^{9 represent} a lone electron pair and an alkali metal Cation forms a salt with the dianion forming, reacts with an alkylene dihalide and a compound of the general 12 3 nen formula I - in which K, R , R, R , η and the dashed line are as indicated above and R and R and H and fi together form a hyphen, X and X mean a sulfur atom, and β, R , R and R ^ form a lone pair of electrons and R and R together form a - ^ CH ^ _s "", where s = 1, 2, 3 or 4. 14. The method according to any one of claims 6 and 11-12, characterized in that a compound of the general formula I, wherein fi, R , R , R, R ^, R ^, R ⁶ , X, η and the dashed line are as indicated in claim 1, R ^ and R ¹⁰ and R and R form a hyphen and R ¹ ^ is hydrogen and Y is a sulfur atom, R? and R ^{8 represent} a lone pair of electrons - if necessary, reacts with an alkylating agent in the presence of an acid binder and thereby sol- 909828/0652 2854119 before compounds eier general formula I are obtained in which R, Ji ¹ , R ² , R ⁵ , R ⁴ , h? _t R ⁶ , X, η and the dashed line, as indicated in claim 1, R and R and R ^Δ and R ⁵ together a hyphen O Q form, Y is sulfur, and R and R ^ are a lone pair of electrons, and & ^{f is} alkyl of 1-4 carbon atoms. 15 · Method according to one of claims 6 and 12- characterized in that one Compound of the general formula I - in which R, R R, D and the dashed line are as indicated in claim 1., R ^y and R together form a hyphen, R denotes hydrogen, X and ϊ denote a sulfur atom, R, R, R, R form a lone pair of electrons, R ^ 'means an alkyl with 1-4 carbon atoms, reacts with an acid anhydride and that such a compound of the general formula Id Id receives, in which R, R κ ² , . , η and the dashed te line as specified in claim 1, 909828/0652 285-113 16. The method according to any one of claims 6 and 12, characterized in that one Compound of the general formula I - in which R, R, R , R , η and the dashed line in claim 1 are given are, R ⁹ and R and R ^Χ and R ¹² together form a hyphen, R ¹⁵ denotes hydrogen, X and Y represent a sulfur atom, R ^, R, R? _t R ^{8 form} a lone pair of electrons, R means alkyl with 1-4 carbon atoms - reacts with a diamine and thereby obtains compounds of the general formula in which R, R ¹ , R, R, η and the dashed line are as indicated above , R and R and R and R ^ together form a hyphen, X and Ϊ denote a nitrogen atom deprived of its pair of electrons, R and R ^ a solitary one tr ο Represent electron pairs, R and R 'hydrogen or Al- 4 7 kyl with 1-4 carbon atoms, R and R together form an optionally substituted - / ^ H ₂ Z ₃ group and s = 1, 2, 3 or 4. . 17 · Method according to one of Claims 6-S. characterized in that one connects 12 3 formation of the general formula I - in which R, R, R, R, η and the dashed line are as indicated in claim 1, r9 and R ¹⁰ and R ¹¹ and R ^{12 form} a hyphen, R ^{13 is} hydrogen, X / Ü ⁴ , R " , R ⁶ J is halogen, Y is one of its solitary ones Electron pair deprived nitrogen atom means, R ^ is alkyl with 1-4 carbon atoms or optionally substituted aryl with 6-10 carbon atoms, .R ^{8 means} alkyl with 1-4 carbon atoms and a halide ion with the positive nitrogen atom forms a salt - with a Alcohol, preferably in the presence of an alkali alkanoate, and such a compound of the general formula I is obtained, in which R, R, R, R, 909828/0652 -χ- / 12 / η and the dashed line are as indicated in claim T., R ^{13 is} hydrogen, R ⁹ and R ¹⁰ and R ¹¹ and R together form a hyphen, X and 1 an oxygen atom deprived of its lone pair of electrons 1 " £ ZT ~ J Q represent, R- ⁷ , R, R ', R signify a lone electron pair, R signifies alkyl with 1-4 carbon atoms or aralkyl with 7-12 carbon atoms. 18. The method according to any one of claims 6-8., Characterized in that one 10 bond of the general formula I - in which R, R ₃ R, R, η and the dashed line are as indicated in claim "1. R ⁷ and R ^AW and R and K ~ form a hyphen, R * means hydrogen, X / R , Ep, RJ means halogen, ϊ a nitrogen atom deprived of its lone pair of electrons represents, R 'alkyl with 1-4 carbon atoms, optionally substituted aryl with 6-10 carbon 8th
represents material atoms, R is alkyl with 1-4 carbon atoms means and a halide ion forms a salt with the positive nitrogen atom - with one containing water Alcohol converts and thereby a compound of general 12 3 Formula I is obtained, wherein R, R, R, R, η and the dashed Line as in claim 1. 'are given, and R denotes hydrogen, R ° and R and R and R together form a hyphen, and X for one of its lonely 25 electron pair deprived nitrogen atom stands, ϊ for an oxygen atom deprived of its lone pair of electrons and R ⁶ , R ⁷ , R ^{8 represent} a lone pair of electrons, } £ alkyl with 1-4 carbon atoms, or optionally substituted aryl with 6-10 carbon atoms and E ⁵ denotes alkyl with 1-4 carbon atoms . 19. The method according to 3inem of claims 6-8. through this marked that a connection 909828/0652 dung the. general formula I - where fi, fi ¹ , fi ² r $ η and the dashed line are as indicated in claim 1, fi9, _fi 10 _{and R} ll _{and R} l2 _{Q ± nQn hyphen} £ _η _ den, K ^{3 is} hydrogen, X / R ⁴ , fi ⁵ , R ⁶ / halogen atom. Y is a nitrogen atom deprived of its lone pair of electrons, R ^{7 is} alkyl with 1-4 carbon atoms, or optionally substituted aryl with 6-10 carbon atoms, fi is ⁸ alkyl with 1-4 carbon atoms and a halide ion. forms a salt with the positive nitrogen atom - reacts with a primary or secondary amine and thereby obtains compounds of the general formula in which fi, R , fi, fi ⁹ , η and the dashed line are given as in claim 1, and fi ⁹ and fi ¹⁰ and fi ¹¹ and fi ^{12 form} a hyphen, fi ¹³ denotes hydrogen and X and Y denote a nitrogen atom deprived of its lone pair of electrons. n
th and fi stands for alkyl with 1-4 carbon atoms, or for optionally substituted aryl with 6-10 carbon atoms, or optionally substituted heteroaryl and R? Hydrogen, or alkyl with 1-4 carbon atoms, fi denotes a lone pair of electrons, fi ^ alkyl with 1-4 carbon atoms, or optionally substituted aryl with 6-10 carbon atoms, fi ⁸ denotes alkyl with 1-4 carbon atoms, and a halide -Ion forms a salt with the positive nitrogen atom and from which the base is optionally released. 20. The method according to any one of claims 6-8, characterized in that a connection 1 2 3 formation of the general formula I- in which'fi, ß, fi, fi, η and the dashed line are given as in Example 1., fi ⁹ and fi ¹⁰ and K ¹¹ and fi ^{12 form} a hyphen, H ^{13 is} hydrogen means, X / R ⁴ , R ⁵ , fi7-halogen represent- 909828/0652 original inspected represents, Y one deprived of its lonely pair of electrons. Nitrogen atom means, R ^{7 means} alkyl with 1-4 carbon atoms, or if necessary substituted aryl with 6-10 carbon atoms, R ^{8 means} alkyl with 1-4 carbon atoms b means atoms and a halide ion forms a salt with the positive nitrogen atom - reacts with a diamine and thereby obtains compounds of the general formula I in which R, R, R ² , R, η and the dashed line in claim 1 are given are, R and R and R and K form a hyphen, Σ and Y represent a nitrogen atom deprived of its lone pair of electrons, R Q [Γ Ο and R / signify an identical pair of electrons, Rr and R signify hydrogen or alkyl with 1-4 carbon atoms 4 7 and R and R ' together an optionally substituted 15 te - ^ EL / group, where m = 2, 5 or 4. 21. The method according to any one of claims 6-20. for the preparation of the compounds of the general formula I - in which η = 0 and R- R , X, Y and the dashed line are as indicated in claim 1, characterized in that compounds of the general formula II are used as starting materials .- in which η β 0, and R, R , R , R and the dashed line are as indicated in claim 1. 22. The method according to any one of claims 6-20. for the preparation of the compounds of the general formula I in which η * 1, and fi, R ¹ - R ¹⁵ , X and Y and the dashed line are as indicated in claim 1, characterized in that such compounds of the general formula are used as starting materials II used wherein η = 1, and R, R ¹ , R ² , R ³ and the dashed line are as indicated in claim 1. 909828/0652 ORIGINAL INSPECTED 23 · Method according to one of claims 6-21. for the preparation of compounds of the general formula I - in which R and R are hydrogen, and R ^ - R ¹⁰ , X and Y and η are as indicated in claim 1., thereby. characterized in that such compounds of general formula II are used as starting materials. 1 2 ^ in which R and R are hydrogen and R _{9 is} Ir and η as stated in claim 1. 24. The method according to any one of claims 6-22. for the preparation of the compounds of the general formula I - in which E is alkyl with 1-4 carbon atoms, R is hydrogen or alkyl with 1-4 carbon atoms 2 10
and E: -R, X, Y and s are as indicated in claim 1, characterized in that compounds of the general formula II are used as starting materials in which R is alkyl with 1-4 carbon atoms, RV / hydrogen or alkyl with 1-4 carbon atoms and R, R · ^ and s as indicated in claim 1 'are. 25- Pharmaceutical preparation characterized by containing a compound of the general formula I wherein the substituents as in Claim 1. are given, or a salt thereof mixed with inert, solid, or liquid pharmaceutical Carriers. 909828/0652 original inspected