DD298389A5 - BASIC DIHYDROPYRIDINES PROCESS FOR THEIR PREPARATION AND THEIR USE AS INTERMEDIATE PRODUCTS - Google Patents

Abstract

The invention relates to novel basic dihydropyridine derivatives of general formula I in which R 1 to R 3, X and Y have the meaning given in the description, processes for their preparation and their use for the preparation of partially known 3-Carbonsaeureaminoalkyl-dihydropyridines. formula

Description

CO ₂ -XY

in which

R ¹ , R ² , R ³ and X have the meaning given in claim 5 and Y - for a group of the formula

-NR ⁷ -Z or phthalimido, in which

R ^{7 is} hydrogen, C 1 -C ₈ alkyl, C 1 -C 6 aralkyl, or phenyl, optionally

is substituted by halogen, nitro, cyano or C ₁ -C ₆ -alkoxy and Z - represents an amine protecting group deblocked with elimination of the amino protecting group.

8. A process for the preparation of compounds of general formula (Vl) according to claim 7, characterized in that one carries out the cleavage of the amino protecting group by hydrogenation with the aid of palladium-charcoal under acidic conditions, when Z is benzyl or in the event that Z represents the phthalimido radical which carries out the splitting off with hydrazine hydrate in organic solvents such as ethers or alcohols.

The invention relates to novel basic dihydropyridine derivatives, to processes for their preparation and to their use for Preparation of partially known 3-Carbonsäureaminoalkyl-dihydropyridines. It is already known that the preparation of 1,4-dihydropyridine-hydroxyalkylamines over certain Dihydropyridinamine

as intermediates runs (see US SN 664 904).

The present invention relates to novel basic dihydropyridines of the general formula (I)

CO ₂ -XY ^(l)

in which

R ¹ - is hydrogen, halogen, alkyl of up to 10 carbon atoms, alkoxy of up to 10 carbon atoms, alkylthio of up to β carbon atoms, cyano, amino, alkylamino of up to 8 carbon atoms, dialkylamino of up to 8 carbon atoms per alkyl group, trifluoromethyl , Trifluoromethoxy, difluoromethoxy or trifluoromethylthio,

R ² and R ^{3 are the} same or different and each

- for hydrogen,

- For cycloalkyl having 3 to 8 carbon atoms or

- straight-chain or branched Alk / I or alkenyl each having up to 18 carbon atoms, which are optionally substituted by halogen, hydroxy, alkoxy having up to 8 carbon atoms, alkylthio having up to 8 carbon atoms,

Alkylcarbonyl having up to 8 carbon atoms in the alkyl radical, carboxy or

Alkoxycarbonyl having up to 8 carbon atoms, cyano or by phenyl or phenoxy groups which are optionally substituted by nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl having up to 4 carbon atoms or alkoxy having up to 4 carbon atoms, or where the radicals cycloalkyl, Alkyl or alkenyl are optionally substituted by a group of formula NR ⁴ R ⁵ , wherein

R ⁴ and R * are the same or different and each is hydrogen, alkyl of up to 8 carbon atoms, aralkyl of 7 to 14 carbon atoms, aryl of 6 to 12 carbon atoms, acetyl or benzoyl, or R ² and R ³ each

- are aryl having 6 to 10 carbon atoms, which are up to 3 times the same or different by nitro, cyano, halogen, alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, alkylthio having up to β carbon atoms, trifluoromethyl, trifluoromethoxy, difluoromethoxy Trifluoromethylthio, amino, alkylamino having up to 4 carbon atoms, dialkylamino having in each case up to 4 carbon atoms per alkyl group, acetylamino or by benzoylamino, or

- represent a 5- to 7-membered saturated or unsaturated heterocyclic ring which may contain, as an additional heteroatom, an oxygen atom, a sulfur atom or an NH or N-alkyl group (1-4 C atoms),

X - for a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical with up to

12 carbon atoms, which is optionally interrupted by an oxygen or sulfur atom or a group NR ⁶ , in the

R ⁶ - may denote hydrogen, alkyl up to 4 carbon atoms, benzyl or phenethyl,

and or

which may be substituted by halogen, hydroxy, acetoxy, carboxy, alkoxycarbonyl having up to 8 carbon atoms or

Phenyl, which is optionally substituted by halogen, alkyl having up to 6 carbon atoms, alkoxy having up to

6 carbon atoms, halomethyl, halomethoxy, hydroxy or cyano, Y - for a group of the formula

-NR ⁷ -Z or phthalimido,

R ⁷ - represents hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -aralkyl or phenyl which is optionally substituted by halogen, nitro, cyano or C 1 -C 6 -alkoxy and

Z - stands for an amino protecting group.

Amino protecting group is within the scope of the invention for the commonly used amino protecting groups. These preferably include: benzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, dichlorobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 2-nitrobenzylnoxycarbonyl, 2-nitro-4,6-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, pentoxycarbonyl, isopentoxycarbonyl, hexoxycarbonyl, cyclohexoxycarbonyl, octoxycarbonyl, 2-ethylhexoxycarbonyl, 2- iodohexoxycarbonyl, 2-bromoethoxycarbonyl, 2-chlorothoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-trichloro-tert-butoxycarbonyl, benzhydryloxycarbonyl, bis (4-niethoxyphenyl) methoxycarbonyl, phenacyloxycarbonyl, 2-trimethylsilylethoxycarbonyl, 2 - (di-n-butylmethylsilyl) ethoxy carbonyl, 2-triphenylsilylethoxycarbonyl, 2- (dimethyl-tert-butylsilyl) ethoxycarb onyl, menthyloxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl, phenoxycarbonyl, tolyloxycarbonyl, 2,4-dinitrophenoxycarbonyl, 4-nitrophenoxycarbonyl, 2,4,5-trichlorophenoxycarbonyl, naphthyloxycarbonyl, fluorenyl-9-methoxycarbonyl, ethylihiocarbonyl, methylthiocarbonyl, butylthiocarbonyl, tert-butylthiocarbonyl, phenylthiocarbonyl, Benzylthiocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, iso -propylaminocarbonyl, formyl, acetyl, propioyl, pivaloyl, 2-chloroacetyl, 2-bromoacetyl, 2-iodoacetyl, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, benzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl, 4-nitrobenzyl, naphthylcarbonyl, phenoxyacetyl, adamantylcarbonyl, dicyclohexylphosphoryl, diphenylphosphoryl, dibenzylphosphoryl, di (4-nitrobenzyl) phosphoryl, phenoxyphenylphosphoryl, diethylphosphinyl, diphenylphosphinyl, phthaloyl or phthalimido.

Of particular interest are the amino protecting groups phthalimido, butoxycarbonyl, tert-butoxycarbonyl. The compounds according to the invention exist in stereoisomeric forms which behave either as image and mirror image (enantiomers) or which do not behave as image and mirror image (diastereomers). The invention relates to both the antipodes and the racemic forms and the diastereomer mixtures. The racemic forms can be as well as the diastereomers in a known manner, for. Separate, for example, by crystallization, chromatography or Craig distribution in the stereoisomerically uniform components (see, El Eliel, Stereochemistry of Carbon Compounds, McGraw Hill, 1962). Preference is given to compounds of the general formula (I) in which R ^{1 is} hydrogen, fluorine, chlorine, bromine, alkyl having up to 8 carbon atoms, alkoxy having up to 8 carbon atoms, alkylthiomite having up to 4 carbon atoms, cyano, amino, alkylamino to 6 carbon atoms, dialkylamino each with up to

6 carbon atoms per alkyl group, trifluoromethyl, trifluoromethoxy, difluoromethoxy or trifluoromethylthio, R ² and R ^{3 are the} same or different and each

- represent hydrogen, cycloalkyl having 3 to 7 carbon atoms or

- represent straight-chain or branched alkyl or alkenyl having up to 14 carbon atoms, which may be substituted by fluorine, chlorine, bromine, hydroxyl, alkoxy having up to 6 carbon atoms, alkylthio having up to 6 carbon atoms, alkylcarbonyl having up to 6 carbon atoms in the alkyl radical , Carboxy, alkoxycarbonyl having up to 6 carbon atoms, by optionally substituted by nitro, trifluoromethyl, methyl or methoxy phenyl or phenoxy radicals, or wherein the radicals alkyl and alkenyl are optionally substituted by cyano and / or by a group of the formula-NR ⁴ R ⁶ , in which

η ⁴ and R ^{6 are the} same or different and each represents hydrogen, alkyl having up to 6 carbon atoms, benzyl, phenethyl, phenyl, acetyl or benzoyl, or R ² and R ³ each

- are phenyl or naphthyl which may be substituted identically or differently up to 3 times by nitro, fluorine, chlorine, bromine, alkyl having up to 4 carbon atoms, alkoxy having up to 4 carbon atoms, alkylthio having up to 4 carbon atoms, trifluoromethyl, trifluoromethoxy, Amino, alkylamino having up to 6 carbon atoms, dialkylamino having in each case up to β carbon atoms per alkyl group, acetylamino or by benzoylamino, or

- represent pyrrolidino, pyridino, morpholine or piperazino.N-C 1 -C 4 -alkylpiperazino.N-C 3 -C 3 -alkyl or N-phenyl-piperazino,

X - for a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical with up to

10 carbon atoms,

which is optionally interrupted by an oxygen or sulfur atom or a group NR ⁶ , in the

R ^e - may denote hydrogen, alkyl up to 2 carbon atoms, benzyl or penethyl,

and or

which may be substituted by halogen, hydroxy, acetoxy, carboxy, alkoxycarbonyl of up to 4 carbon atoms or by phenyl optionally substituted by halogen, alkyl of up to 4 carbon atoms, alkoxy of up to 4 carbon atoms, trifluoromethyl or trifluoromethoxy,

Y - for a group of the formula

-NR ⁷ -Z or phthalimido,

R ⁷ - represents hydrogen, C, -C _e alkyl, C7-C, ₀ aralkyl, or phenyl which is substituted ₄ alkoxy optionally substituted by halogen, nitro, cyano or C, and

Z - represents an amino-protecting group from the group butyloxycarbonyl, tert-butyloxycarbonyl or phthalimido.

Particular preference is given to compounds of the general formula (I) in which R ^{1 is} hydrogen, fluorine, chlorine, alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, alkylthiomite having up to 3 carbon atoms, cyano, amino, alkylamino up to 4 carbon atoms, dialkylamino each having up to 4 carbon atoms per alkyl group, trifluoromethyl, trifluoromethoxy, difluoromethoxy or

Trifluoromethylthio, R ² and R ^{3 are the} same or different and each

- represent hydrogen, cyclopropyl, cyclopentyl or cyclohexyl, or

represent straight-chain or branched alkyl or alkenyl having up to 10 carbon atoms, which may be substituted by fluorine, chlorine, hydroxyl, alkoxy having up to 4 carbon atoms, alkylthio having up to 4 carbon atoms, alkylcarbonyl having up to 4 carbon atoms in the alkyl radical, carboxy, Alkoxycarbonyl having up to 4 carbon atoms, phenoxy, phenyl or the abovementioned radicals alkyl and alkenyl are optionally substituted by a group of the formula -NR ⁴ R ⁶ ,

R ⁴ and R ^{s are the} same or different and are hydrogen, alkyl of up to 4 carbon atoms, benzyl, phenyl or acetyl

mean, or R ² and R ³ respectively

represent phenyl which may be substituted identically or differently up to twice by nitro, fluorine, chlorine, methyl,

Methoxy, trifluoromethyl, trifluoromethoxy, amino, alkylamino having up to 2 carbon atoms or dialkylamino with

each up to 2 carbon atoms per alkyl group, X - represents a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally interrupted by an oxygen or sulfur atom or a group NR ⁶ , in the

R ⁶ - may denote hydrogen, alkyl having up to 2 carbon atoms, benzyl or phenethyl,

and / or may be substituted by hydroxy, carboxy, alkoxycarbonyl having up to 4 carbon atoms or by

Phenyl, which may optionally be substituted by halogen, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Y - for a group of the formula

-NR ⁷ -Zor phthalimido,

R ^{7 is} hydrogen, C 1 -C ₄ -alkyl, C 1 -C ₄ -alkyl or phenyl which is optionally substituted by fluorine, chlorine, nitro, cyano,

Methoxy, ethoxy or propoxy is substituted and Z - is tert-butyloxycarbonyl or phthalimido

 The compounds of the general formula (I) according to the invention

O ₂ -XY

in which

R ¹ , R ² , R ³ , X and Y have the abovementioned meaning,

one obtains by one

Aldehydes of the general formula (II)

(ID

CHO

in which

R ^{1 has} the meaning given above,

with β-ketocarboxamides of the general formula (III)

N-OC

in which

R ² and R ^{3 have} the abovementioned meaning,

optionally after isolation of the resulting ylidene compounds of general formula (IV)

(IV)

in which

R ¹ , R ² and R ^{3 have} the abovementioned meaning, with aminocrotonic acid esters of the general formula (V)

(V)

in which

X and Y have the meaning given above '· η,

optionally in the presence of inert organic solvents at temperatures between 1O ⁰ C and 15O ⁰ C reacted.

The synthesis of the compounds according to the invention can be represented by the following formula scheme:

CHO

* Ύ

COO-CH ₂ -CH ₂ -

AIs solvents may be water or any inert organic solvents that may be present under the reaction conditions

Don `t change. These include, preferably, alcohols, such as methanol, ethanol, propanol, isopropanol, ethers, such as diethyl ether,

Dioxane, tetrahydrofuran, glycol monomethyl ether or glycol dimethyl ether, or amides such as dimethylformamide, Dimethylacetamide or hexamethylphosphoric triamide, or glacial acetic acid, dimethyl sulfoxide, acetonitrile or pyridine. The reaction temperatures can be varied within a substantial range. In general, one works between + 1O ⁰ C.

and + 15O ⁰ C, preferably between +20 "C and +100" C, in particular at the boiling temperature of the respective solvent.

The reaction can be carried out at normal pressure, but also at elevated or reduced pressure. In general

you work at normal pressure.

The ratio of the substances involved in the reaction is arbitrary. In general, however, one works with molar amounts of Reactants. The isolation and purification of the substances according to the invention is preferably carried out such that the Solvent distilled off in vacuo and the optionally crystalline obtained after cooling with ice from a

recrystallized suitable solvent. In some cases, it may be necessary to the compounds of the invention by

Purify chromatography. The aldehydes of the general formula (II) used as starting materials are known or can be prepared by known methods

(DOS 2165260; 2401665; T.D. Harris, G.P. Roth, J. Org. Chem. 44,2004 [1979]; WJ. Dale, H.E. Hennis, J. Am.

Chem. Soc. 78, 2543 (1956); Chem. Abstr. 59, 133929 [1963]). The compounds of the general formula (III) are known or can be prepared by known methods

(DOS 1142859, EP 220653).

The ylidene-.beta.-ketocarboxylic acid derivatives of the general formula (IV) are known or can be prepared by known methods

(Jones, The Knoevenagel Condensation, Organic Reactions, Vol. XX, 204 (1967)).

The enaminocarboxylic acid esters of the general formula (V) used are known or can be prepared by known methods

F. A. Glickman, A. C. Cope, J. Am. Chem. Soc., 67, 101711945)).

The compounds of the general formula (I) according to the invention are thus intermediates z. B. for the representation of

3-Carbonsäure-aminoalkyl-dihydropyridines of the general formula (Vl).

N-OC

COO-X-NH ₂

in which

R ¹ , R ', R ³ and X are as defined above, usable. The compounds of the general formula (V!) Are obtained by reacting compounds of the general formula (I) under Cleavage of the amino protecting group in known per se, deblocked, for example by hydrogenation with the aid of Palladium / animal charcoal, under acidic conditions when Z is benzyl, or when Z is the phthalimido radical, with Hydrazine hydrate in organic solvents such as ethers, e.g. Tetrahydrofuran or dioxane, or alcohols such as e.g. methanol, Ethanol or isopropanol. The compounds of general formula (VI) are known in some cases (see EP 179386). The compounds of the general formula (VI) and their physiologically acceptable salts are used in the Combat hypertension or heart failure. embodiments A. Preparation of the new intermediates

Example 1 4- (3-Chlorophenyl) -1,4-dihydro-2,6-dimethyl-pyridine-3-carboxylic acid (2-phthalimidoethyl) -ester-5-carboxylic acid-cyclopropylamide

COO-CH ₂ -CH ₂ -

7.29 g (27.6 mmol) of S-chloro-benzylidene-acetoacetic acid-cyclopropylamide are used together with 7.56 g (27.6 mmol)

Aminocrotonsäure- (2-phtha! Imidoetiiyl) ester stirred for 24 hours under reflux. After cooling and concentration of the Reaction solution, the product mixture by column chromatography on silica gel (40-63 pm) with the mobile phase mixture Methylene chloride / methanol in a volume ratio of 30: 1 purified. The amorphous substance obtained after evaporation of the eluate

is dried in vacuo.

Yield: 7.8 g (54.5% of theory) R ₁ : 0.51 (methylene chloride / methanol = 10: 1) Analogously to Example 1, the examples listed in Table 1 are prepared: Table 1 Example number,

R ² -H

F [ ⁰ C]

2 3 4 5

O-CF;

o-CF _:

m-Cl

m-Cl

m-Cl o-CF ₃ o-CFo

-CH ₂ -CH ₂ - 120-122 0.49 -CH ₂ -CH ₂ - 0, ₅ 2 C ₂ H ₅ -CH ₂ -CH ₂ - 0.54 C ₂ H ₅ -CH-CH- I 0.57 I CH ₃ 114 D- -CH-CH ₂ - 0.51 CH ₃ C ₂ H ₅ -CH-CH ₂ - 0.44

CH

-CH-CH ₂ -

CHO

112

R _f * = HPTLC finished boards; Silica gel 60 F ₂₅₄ ; Solvent: methylene chloride / methanol 10: 1

Use of the new intermediates for the preparation of dihydropyridine active ingredients

Example 9

4- (3-chlorophenyl) -1,4-dihydro-2,6-dimethyl-pyridine-3-carboxylic acid (2-aminoethyl) ester-5-carboxylic acid cyclopropylamide

CO ₂ -CH ₂ -CH ₂ -NH ₂ H ₃

A solution of 6.6 g (12.7 mmol) of 1,4-dihydro-2,6-dimethyl-4- (3-chlorophenyl) -pyridine-3-carboxylic acid (2-phthalim) -dethyD-ester-5-carboxylic acid cyclopropylamide and 63.5 mmol hydrazine hydrate are refluxed for 1 hour. After cooling, the precipitate is filtered off and washed with methylene chloride. The filtrate is concentrated in vacuo and the residue is first taken up in methylene chloride, then washed once with 2N potassium hydroxide solution and 3 times with water. The solution is dried over sodium sulfate and concentrated in vacuo. The product crystallizes on trituration with ether,

Yield: 3.6 g (72.7% of theory)

M .: 168-170 ⁰ C

Ri = 0.19 (methylene chloride / methanol 5: 1)

The examples listed in Table 2 were prepared analogously to Example 9:

Table 2! Example no.

R ² -HN

OO-X-NH-

F [ ⁰ C]

10 11 12 1314 15 16

m-Cl

ο -CF

m-Cl

m-Cl

m-Cl

m-Cl

D-

^C 2 ^H 5

C ₂ H ₅

D-

-CH ₂ -CH ₂ - -CH ₂ -CH ₂ - -CH ₂ -CH ₂ - -CH-CH-

I ²

CH ₃ -CH-CH-

I ²

CH ₃ -CH-CH-

I ²

CH ₃

-CH-CH ₂ -CHO

136-139 196-198 218-220 154-164

163-167

0.20 0.18 0.17 0.57

0.15 0.33 0.15

R _f * = HPTLC finished boards; Silica gel 60 F ₂₅₄ ; Solvent: methylene chloride / methanol 10: 1

Continuation of Table 2 Be. No. R ¹ R ² JC F [ ⁰ C] R _f *

0-CF ₃ C ₂ H ₅ -CH-CH ₂ - 93-95 0.32

CH ₃

o-CFo V "-CH-CHO-125-127 0.34

V-

CH ₃

0-CF3 V- -CH-CH _2-0.16

CH ₃

R _f * = HPTLC finished boards; Silica gel 60 F ₂₅₄ ; Solvent: methylene chloride / methanol 5: 1

ω oo to

Claims (4)

1. Basic Dihydropyridines of the General Formula (I) CO ₂ -XY ^(l) in which R ¹ - represents hydrogen, halogen, alkyl having up to 10 carbon atoms, alkoxy having up to 10 carbon atoms, alkylthio having up to 6 carbon atoms, cyano, amino, alkylamino having up to 8 carbon atoms, dialkylamino having in each case up to 8 carbon atoms per alkyl group, Trifluoromethyl, trifluoromethoxy, difluoromethoxy or trifluoromethylthio, R ² and R ^{3 are the} same or different and each - for hydrogen, - For cycloalkyl having 3 to 8 carbon atoms
or - straight-chain or branched alkyl or alkenyl with each 18 carbon atoms which are optionally substituted by halogen, hydroxy, alkoxy having up to 8 carbon atoms, alkylthio having up to 8 carbon atoms, alkylcarbonyl having up to 8 carbon atoms in the alkyl radical, carboxy or alkoxycarbonyl having up to 8 carbon atoms, cyano or by phenyl or phenoxy groups which are optionally substituted by nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl of up to 4 carbon atoms or alkoxy of up to 4 carbon atoms, or wherein the radicals cycloalkyl, alkyl or alkenyl are optionally substituted by a group of formula -NR ⁴ R ⁵ are substituted
wherein R ⁴ and R ^{5 are the} same or different and each is hydrogen, alkyl of up to 8 carbon atoms, aralkyl of 7 to 14 carbon atoms, aryl of 6 to 12 carbon atoms, acetyl or benzoyl,
or R ² and R ³ respectively - represent aryl having 6 to 10 carbon atoms, up to 3 times the same or different by nitro, cyano, halogen, alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, alkylthio having up to 6 carbon atoms, trifluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylthio, amino, alkylamino with up to 4 carbon atoms, dialkylamino each having up to 4 carbon atoms per alkyl group, acetylamino or substituted by benzoylamino, or - represent a 5- to 7-membered saturated or unsaturated heterocyclic ring which may contain, as an additional heteroatom, an oxygen atom, a sulfur atom or an NH or N-alkyl group (1-4C atoms), X -. is a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 12 carbon atoms, which is optionally interrupted by an oxygen or sulfur atom or a group NR ⁶ , in which R ^{6 is} hydrogen, alkyl up to 4 carbon atoms, benzyl or phenethyl, and / or which may be substituted by halogen, hydroxy, acetoxy, carboxy, alkoxycarbonyl of up to 8 carbon atoms or phenyl optionally substituted by halogen, alkyl of up to 6 carbon atoms, alkoxy of up to 6 carbon atoms, halomethyl, halomethoxy, hydroxy or cyano . Y - for a group of the formula -NR ⁷ -Z or stands for phthalimido, wherein R ⁷ - represents hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -aralkyl or phenyl, which may be present is substituted by halogen, nitro, cyano or Ci-C _e alkoxy and Z - stands for an amino protecting group. 2. Compounds of the general formula (I) according to claim 1, in which R ¹ , R ² , R ³ , X and Y have the meaning given in claim 1, and Z represents one of the following amino-protecting groups: Benzyloxycarbonyl-bromobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, dichlorobenzyloxycarbonyl, S-S-dimethoxybenzyloxycarbonyl, S, - ^, methoxybenzyloxycarbonyl, ^, - dimethoxybenzyloxycarbonyl, 4-hydroxybenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 2-nitrobenzylcarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyljSAB- Trimethoxybenzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, pentoxycarbonyl, isopentoxycarbonyl, hexoxycarbonyl, cyclohexoxycarbonyl, octoxycarbonyl, 2-ethylhexoxycarbonyl, 2-iodohexoxycarbonyl, 2-bromoethoxycarbonyl, 2-chloroethoxycarbonyl, 2,2,2- Trichloroethoxycarbonyl, 2,2,2-trichlorotertbutoxycarbonyl, benzhydryloxycarbonyl, bis- (4-methoxyphenyl) methoxycarbonyl, phenacyloxycarbonyl-trimethylsilylethoxycarbonyl, di-n-butyl-methylsilyethoxycarbonyl, -triphenylsilyl-thoxycarbonyl, dimethyl-tert-butylsily-ethoxycarbonyl, menthyloxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl, Phenoxycarbonyl, tolyloxycarbonyl, 2,4-dinitrophenoxycarbonyl, 4-nitrophenoxycarbonyl, 2,4,5-trichlorophenoxycarbonyl, naphthyloxycarbonyl, fluorenyl-9-methoxycarbonyl, ethylthiocarbonyl, methylthiocarbonyl, butylthiocarbonyl, tert-butylthiocarbonyl, phenylthiocarbonyl, benzylthiocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, iso -propylaminocarbonyl, formyl, acetyl, propionyl, pivaloyl, 2-chloroacetyl, 2-bromoacetyl, 2-iodoacetyl, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, benzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl, 4-nitrobenzyl, naphthylcarbonyl, phenoxyacetyl, adamantylcarbonyl, dicyclohexylphosphoryl, diphenylphosphoryl, dibenzylphosphoryl, di (4-nitrobenzyl) phosphoryl, phenoxyphenylphosphoryl, diethylphosphinyl, diphenylphosphinyl, phthaloyl or phthalimido. 3. Compounds of general formula (I) according to claim 1, in which R ¹ - is hydrogen, fluorine, chlorine, bromine, alkyl of up to 8 carbon atoms, alkoxy of up to 8 carbon atoms, alkylthio of up to 4 carbon atoms, cyano, amino, alkylamino of up to 6 carbon atoms, dialkylamino of up to 6 each Carbon atoms per alkyl group, trifluoromethyl, trifluoromethoxy, difluoromethoxy or trifluoromethylthio, R ² and R ^{3 are} the same o ^r are "erschieden and each - represent hydrogen, cycloalkyl having 3 to 7 carbon atoms or - represent straight-chain or branched Aikyl or alkenyl having up to 14 carbon atoms, which may be substituted by fluorine, chlorine, bromine, hydroxy, alkoxy having up to 6 carbon atoms, alkylthio having up to 6 carbon atoms, alkylcarbonyl, having up to 6 carbon atoms in Alkyl radical, carboxy, alkoxycarbonyl having up to 6 carbon atoms, by optionally substituted by nitro, trifluoromethyl, methyl or methoxy phenyl or phenoxy radical, or wherein the radicals alkyl and alkenyl are optionally substituted by cyano and / or by a group of formula NR ⁴ R ⁶ , in which R ⁴ and R ^{5 are the} same or different and each represents hydrogen, alkyl of up to 6 carbon atoms, benzyl, phenethyl, phenyl, acetyl or benzoyl, or R ² and R ³ each - are phenyl or naphthyl which may be substituted identically or differently up to 3 times by nitro, fluorine, chlorine, bromine, alkyl having up to 4 carbon atoms, alkoxy having up to 4 carbon atoms, alkylthio having up to 4 carbon atoms, trifluoromethyl, trifluoromethoxy , Amino, alkylamino having up to 6 carbon atoms, dialkylamino having in each case up to 6 carbon atoms per alkyl group, acetylamine or by benzoylamino, or - for pyrrolidino, pyridino, morpholino or for piperazines), N-Cr-C ^ alkylpiperazino, N-Cy-Cg-aralkyl or N-phenyl-piperazino, X - is a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 10 carbon atoms, which is optionally interrupted by an oxygen or sulfur atom or a group NR ⁶ , in the R ⁶ - may denote hydrogen, alkyl up to 2 carbon atoms, benzyl or phenethyl, and / or which may be substituted by halogen, hydroxy, acetoxy, carboxy, alkoxycarbonyl having up to 4 carbon atoms or by phenyl optionally substituted by halogen, alkyl having up to 4 carbon atoms, alkoxy having up to 4 carbon atoms, trifluoromethyl or trifluoromethoxy, Y - for a group of formulas -NR ⁷ -Z or stands for phthalimido, wherein R ^{7 is} hydrogen, C ₁ -C ₆ alkyl, C ₁ -C 8 aralkyl or phenyl, if appropriate is substituted by halogen, nitro, cyano or C ₄ -C ₄ -alkoxy and Z - represents an amino-protecting group from the group consisting of tert-butyloxycarbonyl, phthalimido or Butyloxycarbonyl stands.
4. Compounds of general formula (I) according to claim 1, in which R ¹ - represents hydrogen, fluorine, chlorine, alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, alkylthio having up to 3 carbon atoms, cyano, amino, alkylamino having up to 4 carbon atoms, dialkylamino having in each case up to 4 carbon atoms per alkyl group, trifluoromethyl, trifluoromethoxy, difluoromethoxy or trifluoromethylthio,
R ² and R ^{3 are the} same or different and each - represent hydrogen, cyclopropyl, cyclopentyl or cyclohexyl, or - are straight-chain or branched alkyl or alkenyl having up to 10 carbon atoms, which may be substituted by fluorine, chlorine, hydroxy, alkoxy having up to 4 carbon atoms, alkylthio having up to 4 carbon atoms, alkylcarbonyl having up to 4 carbon atoms in the alkyl radical, carboxy, alkoxycarbonyl having up to 4 carbon atoms, phenoxy, phenyl or the abovementioned radicals alkyl and alkenyl are optionally substituted by a group of the formula-NR ⁴ R ⁵ , wherein R ⁴ and R ^{B are the} same or different and denote hydrogen, alkyl having up to 4 carbon atoms, benzyl, phenyl or acetyl, or R ² and R ³ respectively are phenyl which may be substituted identically or differently up to twice by nitro, fluorine, chlorine, methyl, methoxy, trifluoromethyl, trifluoromethoxy, amino, alkylamino having up to 2 carbon atoms or dialkylamino having in each case up to 2 carbon atoms per alkyl group, X - is a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms which is optionally interrupted by an oxygen or sulfur atom or a group NR ⁶ , in which R ^{8 is} hydrogen, alkyl is up to 2 Carbon atoms, benzyl or phenethyl, and / or may be substituted by hyd. oxy, carboxy, alkoxycarbonyl having up to 4 carbon atoms or by phenyl, which may optionally be substituted by halogen, methyl, methoxy, trifluoromethyl or trifluoromethoxy, Y - for a group of formulas -NR ⁷ -Z or phthalimido, wherein R ^{7 is} hydrogen, C 1 -C 4 alkyl, C 7 -C 9 aralkyl, or phenyl, optionally is substituted by fluorine, chlorine, nitro, cyano, methoxy, ethoxy or propoxy and Z - is tert-butyloxycarbonyl or phthalimido. 5. Process for the preparation of basic dihydropyridines of the general formula (I) O ₂ -XY in which R ¹ - for hydrogen, halogen, alkyl of up to 10 carbon atoms, alkoxy of up to 10 carbon atoms, alkylthio of up to 6 carbon atoms, cyano, amino, alkylamino of up to 8 carbon atoms, dialkylamino of up to 8 carbon atoms per alkyl group, trifluoromethyl , Trifluoromethoxy, difluoromethoxy or trifluoromethylthio, R ² and R ^{3 are the} same or different and each - for hydrogen, for cycloalkyl of 3 to 8 carbon atoms or - for straight-chain or branched alkyl or alkenyl in each case 18 carbon atoms which are optionally substituted by halogen, hydroxy, alkoxy having up to 8 carbon atoms, alkylthio having up to 8 carbon atoms, alkylcarbonyl having up to 8 carbon atoms in the alkyl radical, carboxy or alkoxycarbonyl having up to 8 carbon atoms, cyano or by phenyl or phenoxy groups which are optionally substituted by nitro, cyano, trifluoromethyl, trifluoromethoxy, alkyl of up to 4 carbon atoms or alkoxy of up to 4 carbon atoms, or wherein the radicals cycloalkyl, alkyl or alkenyl are optionally substituted by a group of formula -NR ⁴ R ⁵ are substituted
wherein R ⁴ and R ^{5 are the} same or different and each is hydrogen, alkyl of up to 8 carbon atoms, aralkyl of 7 to 14 carbon atoms, aryl of 6 to 12 carbon atoms, acetyl or benzoyl,
or R ² and R ³ respectively - were aryl of 6 to 10 carbon atoms, up to 3 times, identically or differently, by nitro, cyano, halogen, alkyl having up to 6 carbon atoms, alkoxy having up to C carbon atoms, alkylthio having up to 6 carbon atoms, trifluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylthio, amino, alkylamino with bis to 4 carbon atoms, dialkylamino having up to 4 carbon atoms per alkyl group, acetylamino or benzoylamino substituted, or - represent a 5- to 7-membered saturated or unsaturated heterocyclic ring which may contain, as an additional heteroatom, an oxygen atom, a sulfur atom or an NH or N-alkyl group (1-4 C atoms), X - is a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 12 carbon atoms, which is optionally interrupted by an oxygen or sulfur atom or a group NR ⁶ , in which R ^{6 is} hydrogen, alkyl having up to 4 carbon atoms, Benzyl or phenethyl, and / or which may be substituted by halogen, hydroxy, acetoxy, carboxy, alkoxycarbonyl having up to 8 carbon atoms or phenyl optionally substituted by halogen, alkyl having up to 6 carbon atoms, alkoxy having up to 6 carbon atoms, halomethyl, halomethoxy, hydroxy or cyano . Y - for a group of the formula -NR ⁷ -Z or stands for phthalimido,
wherein R ⁷ - is hydrogen, C ₁ -Ce-AIkYl, CT-Cu-aralkyl or phenyl, which is optionally substituted by halogen, nitro, cyano or C ₁ -C ₆ -alkoxy, and Z - represents an amino-protecting group, characterized in that aldehydes of the general formula (II) (ID CHO in which R ^{1 has} the abovementioned meaning, with β-ketocarboxamides of the general formula (III) in which R ² and R ^{3 have} the abovementioned meaning, if appropriate after isolation of the resulting ylidene compounds of the general formula (IV) / R ² (IV) 0-N 'H3 in which R ¹ , R ² and R ^{3 have} the abovementioned meaning, with aminocrotonic acid esters of the general formula (V) Η, Ο ^ Ν NH ₂ (V) in which X and Y have the abovementioned meaning, optionally in the presence of inert organic solvents at temperatures between 10 ⁰ C and 150 ⁰ C. 6. Use of compounds of general formula (I) according to claim 1 as intermediates in the preparation of 3-carboxylic acid aminoalkyl-dihydropyridines of the general formula (Vl) (Vl) in which R ¹ , R ² , R ³ and X have the meaning given in claim 1. -β- 298 389 7. Process for the preparation of compounds of the general formula (VI), (Vl) in which R ¹ , R ² , R ³ and X have the meaning given in claim 5, characterized in that basic dihydropyridines of the general formula (I)