DD267045A1 - PROCESS FOR THE PREPARATION OF DIHYDROPYRIDINE DERIVATIVES - Google Patents

Abstract

The invention relates to a process for the preparation of dihydropyridine derivatives. The aim of the invention is to provide a process for the preparation of N-furfuryl-1-alkyl, aralkyl, aryl, hetaralkyl-4-alkyl, aralkylthio-6-amino-3-cyano-1,2-dihydro- To develop 2-oxo-pyridine-4-carboxylic acid amides. These dihydropyridine derivatives can be used as organic intermediates for further syntheses. They are particularly suitable for the preparation of potentially biologically active compounds. According to the invention, the dihydropyridine derivatives of the general formula III in which R is an alkyl or aralkyl radical and R 1 is an alkyl, aralkyl, aryl or heteroalkyl radical can be prepared by reacting the acrylamides of the general formula I in which R has the above meaning with cyanacetamides of the general formula II in which R1 is as defined above.

Description

To this 1 page Formoln

Field of application of the invention The invention relates to a process for the preparation of N-FurfuryM-alkyl, aralkyl, aryl, hetaralkyl-4-alkyl, aralkylthio-e-amino

3-cyano-1,2-dihydro-2-oxo-4-carboxamides pyridine.

Dinse dihydropyridine derivatives can be used as organic intermediates for further syntheses. you are

especially suitable for the preparation of potentially biologically active compounds.

Characteristic of the known state of the art

N-Furfuryl-1-alkyl, aralkyl, aryl, hetaralkyl-4-alkyl, aialkylthlo-e-amino-S-cyano-i ^ -dlhydro ^ -oxo-pyridine ^ - carboxamides are not yet known.

Object of the invention The aim of the invention is the development of a process for the preparation of new pharmaceutical active ingredients. Explanation of the essence of the invention The object of the invention is to provide a process for the preparation of N-furfuryl-1-alkyl, aralkyl, aryl, hetaralkyl-4-alkyl,

aralkylthio-e-amino-S-cynno-i ^ -dihydro ^ -oxo-pyrldin ^ -carboxamides to develop.

According to the invention, the dihydropyridine derivatives of general formula III, in which R is an alkyl or aralkyl radical and R ¹

represent an alkyl, aralkyl, aryl or heteroalkyl radical, by reacting the acrylamides of the general formula I in which R has the above meaning, with cyanoacetamides of the general formula II in which R ^{1 is} as defined above, are prepared.

The reactions are carried out in organic solvents, preferably in dimethylformamide. It is necessary

a base, preferably potassium carbonate. The reaction temperatures are at the boiling temperatures of the solvents used. The reaction times are only a few minutes. After cooling the reaction mixtures to 20 ° C they are mixed with water and acidified with dilute mineral acid. The precipitates formed are filtered off, washed with water and recrystallized from organic solvents for further purification.

Ausfflhrungsbelsplole Embodiment plinth 1

N-Furfuryl-e-amino-S-cyano-i-dihydro-i-furfuryl-methylthio-oxo-pyridine-S-carboxamide A mixture of 0.01 mol of N-furfuryl-2-cyano-3,3 -bis (methylthio) acrylamide, 0.01 mol of N-furfurylcyanacetamide, 2 g of potassium carbonate and 10 ml of dimethylformamide is refluxed for 2 minutes. It is allowed to cool to 20 ° C, the mixture is mixed with 100ml of water, acidified with dilute hydrochloric acid, then stirred for 10 minutes, the precipitate is filtered off, washed with water and crystallized from dimethylformamide / ethanol

Yield: 57% of the tenth mp .; 149-150 ⁰ C

C ₁ BH ₁₆ N ₄ O ₄ S (384.4) Boron C 56.26 H 4.1.1 S 8.33

Gef. C 66.50 H 4.40 S 7.99

IR (KBr): NH ₂ 3480, 3440, NH 3300, CN 2220, C01630Cm "¹;

¹ H-NMR (DMSOd ₀ ): CH ₃ 2.32 (β, 3H), CH ₂ 4.28 (d, 2H), CH ₂ 5.13 (8.2H), furan protons; H-3.4C, 6.28 (m, 4H), H-5C, 5C'7.48 (m, 2H), NH 8.78 (broad signal) ppm.

Implementation Bills 2 N-furfuryl-e-amino-S-cyano-i ^ -dihydro ^ ethylthio ^ -oxo-i-furfuryl-pyridin-S-carboxylic acid amide

0.01 mol of N-furfuryl-2-cyano-3,3-bis (ethylth! O) -acrylamide and 0.01 mol of N-furfuryl-cyanacetamid are reacted, as described in Example 1

Yield: 60% of the tenth M .: 178-179 ⁰ C

CtBHteN ^ S (398.5) Boron C 67.28 H 4.62 N 14.07 S 8.04

Gef. C 57.40 H 4.60 N 13.88 S 8.18

Execution cover 3 N-furfuryl-6-amlno-4-ben2ylthlo-3-cyano-1,2-dihydro-1-furfuryl-2-oxo-pyridln-5-carbon6äureamid

0.01 mol of N-furfuryl-3,3-bi8 (benzylthio) -2-cyano-acrylamide and 0.01 mol of N-furfuryl-cyanacetamid are reacted as described in Example 1

Yield: 50% d. Th. Mp .: 198-200 ⁰ C

C ₂₄ H ₂₀ N ₄ O ₄ S (^ 60.5) boron. S 8.95

Gef. S 8.30

Execution template 4 N-furfuryl-e-amlno-i-beniyl-S-cyano-i ^ ^ -methylthio -dlhydro ^ -oxo-pyridin-B-carboxamide

0.01 mol of N-furfuryl-2-cyano-3,3-bi8 (methylthio) acrylamide and 0.01 mol of N-benzyl-cyanoacetamide are reacted as described in Example 1

Yield: 54% D. Th .: mp. 167-188 ⁰ C

C _n H ₁₈ N ₄ O ₃ S (394.5) The. C 60.91 H 4.68 N 14.21 S 8.12,

Gef. C 60.39 H 4.42 N 14.00 S 7.99

Execution label S N-rurfuryl-e-amlno-i-benzyl-S-cyano-i ^ -dihydro ^ ethylthio ^ -oxo-pyrldin-B-carbonsöureamid

0.01 mol of N-furfuryl-2-cyano-3,3-bis (ethylthio) acrylamide and 0.01 mol of N-benzyl cyanoacetamide are reacted as described in Example 1

Yield: 50% d. Th. Mp .: 226-228 ⁰ C

C ₂₁ H ₂₀ N ₄ O ₃ S (408.5) Calcd. C 81.78 H 4.90 N 13.72 S 7.84

Gef. C61.26 H4.81 N 13.33 S 7.65

09S

S JJ -0II ₂ rqHG0GCG.n ^ cCSR) ₂ + R ¹ NHGOGH ₂ GN

⁰ - RSH

I II

R-N G-GN

H ₂ NG G-SR

CONHGH ₂ -U J) 0

III

Claims (2)

1. A process for the preparation of Dihydropyridinderivaten of the general formula III, in which R is an alkyl or aralkyl radical and R ^{1 is} an alkyl, aralkyl, aryl or Hetaralkylrest, characterized in that acrylamides of the general formula I, in the R has the above meaning, with Cyanacetamiden the general formula II, in which R ^{1 is} as defined above, urngesetzt. 2. The method according to claim 1, characterized in that the reactions are carried out in the presence of a base.