HU201295B - Process for producing 2-substituted 3-oxobutyric acid derivatives - Google Patents

Abstract

The present invention relates to compounds of formula (I) wherein R3 is nitrophenyl, C5-7cycloalkyl or C7-C9 bicycloalkyl, and R4 is C1-4 alkyl optionally substituted with halogen, provided that if \ t R4 is unsubstituted alkyl, R11 is other than nitrophenyl. The novel compounds are the starting materials for the preparation of therapeutic compounds for the treatment of cardiovascular diseases. R3 (III) Principal of the description: page 2, Figure 1 EN 201 295 B -1-

Description

The present invention relates to novel 2-substituted 3-oxo-butyric acid derivatives of the general formula (III). In the general formula (III)

R ³ is mitrophenyl, C 5 -C 7 cycloalkyl, or C 7 -C 9 bicycloalkenyl, and

R ^{4 is} C 1 -C ⁴ alkyl substituted with halogen, provided that when R ⁴ is unsubstituted alkyl, R ³ is not nitrophenyl.

Compounds of formula (III) may be prepared using the known Knovenagel reaction; during the preparation, the corresponding substituted aldehyde of the formula R ³ CHO - wherein:

R ³ is condensed under the conditions of the above Knoevenagel reaction with an acetic acid ester of the formula CH ³ COCH ² COOR ⁴

R ⁴ has the meaning given above -.

DE-OS 26 58 804. Disclosure of the Invention discloses the preparation of compounds of the formula wherein R ^{4 is} inter alia alkyl and R ^{3 is} aryl or heterocyclic. 25

Compounds of formula (ΙΠ) are starting materials for the preparation of 1,4-dihydropyrid-5-ylcycloimidate esters of formula (I). In the formula (I), R ³ and R ⁴ are as defined above, R and R ¹ are each independently H or C 1-4 alkyl and one of them may be lower alkyl substituted by lower alkoxy,

R ² is lower alkyl, phenyl or thienyl;

^R5 is lower alkyl or phenyl, m is 0 or 1, n is 1. The compounds of formula (I) for the treatment of heart and vascular diseases - suitable - for example the treatment of angina and hypertension. 40

The following examples illustrate the present invention in more detail.

In the examples, the melting point values were not corrected.

Example 1

Ethyl a-acetyl-3-nitrocinnamate (Reference Example)

A mixture of 151 g (1.0 mol) of m-nitrobenzaldehyde, 130 g (1.0 mol) of ethyl acetate in acetic acid, 4 ml of piperidine and 12 ml of glacial acetic acid was refluxed in 200 ml of benzene while 19 ml of water were refluxed. remove with Dean5 Stark water separator. The dark brown reaction mixture was cooled to room temperature and washed several times with water. The reaction mixture was concentrated in vacuo to give a dark yellow solid. The solid was recrystallized from ethanol to give 182 g (69% yield) of a yellow solid, mp 103-106 ° C. Literature: S.Ruhemann, J.Chem.Soc., Vol. 83,717 (1903) 110 ^e C.

The compounds of formula (III) are also prepared according to the procedure of Example 1; these are summarized in the table below:

Table III Compounds of Formula III

Example R ³ '' Fp.:(°C/13,3Pa) R ⁴ Op :: ('C) 2. cyclohexyl ethyl 160-170 - 2,2-bicyclo ethyl 134-140 - heptyl 3. m-nitrophenyl 2-chloroethyl 68-76

Patent Claim Point

Claims (1)

Process 2-Substituted 3-oxo-butyric acid derivatives of formula (III) R ³ is nitrophenyl, C 5 -C 7 cycloalkyl, or C 7 -C 9 bicycloalkyl, and R ⁴ is C 1 -C 4 alkyl optionally substituted with halogen, provided that when R ⁴ is unsubstituted alkyl, R 4 is for preparation other than nitrophenyl, characterized in that an aldehyde of formula R 4 -CHO, wherein R ³ is subjecting the condensation reaction of the Knoevenagel reaction to the acetone ester of the formula CH ¹ COCH ² COOR ⁴ wherein R ⁴ is as defined herein.