DD205166A1 - PROCESS FOR PREPARING FUROYL DIHYDROPYRAZOLO (5.1-B) THIAZOLCARBONIC ACID ESTERS - Google Patents

Abstract

The aim of the invention is to develop a process for the preparation of substituted 5-furoyl-6-imino-5,6-dihydro-pyrazolo (5,1-b) thiazole-7-carboxylic acid esters. The furoyldihydropyrazolo (5,1-b) thiazolcarbonsaeureester of the general formula III, in which R is an alkyl radical, R is a highly substituted 1 for an optionally substituted phenyl radical, an alkyl radical or an alkoxycarbonyl radical and R 2 is a hydrogen atom or an acetyl group, by Reaction of the 3-amino-2-furoyl-5-thioxo-gamma-high-3-pyrazoline-4-carboxylic acid esters of the general formula I, in which R has the above meaning, with carbonyl compounds of the general formula II, in which R is H and R 1 2 are as defined above and X is a halogen atom. These furoyldihydropyrazolo (5,1-b) thiazolecarboxylic acid esters can be used as organic intermediates for further syntheses. They are particularly suitable for the preparation of further derivatives of Furoyldihydropyrazolo (5,1-b) thiazolcarbonsaeureester.

Description

-'- 240 0 08 2

Process for the preparation of furoyl-hydroxyhydrazoloquio-b] -thiazolecarboxylic acid ee stern

Field of application of the invention

The invention relates to a process for the preparation of substituted ^ -Puroyl-S-imino- ^ -di-diiiydro-pyrazolo-J3 »1-t0tihiazol-7-carboxylic acid esters. '' These Furoyldihydropyrazolo ^ ii-b ^ thiazolcarbonsäureester can as organic intermediates for further syntheses be used. They are particularly suitable for the preparation of further derivatives of the uroyldihydropyrazolo [5,1-b] thiazole-carboxylic acid esters,

Characteristic of the known technical solutions

Substituted 5-Euroyl-6-imino-5,6-dihydro-pyrazolo [5,1-b] thiazole-7-carboxylic acid esters are not yet known,

Object of the invention

I ';

The object of the invention is to develop a process for the preparation of these substituted 5-3? Uroyl-6-imino-5,6-dihydropyrazol: j.o [5,1-b3taiiazole-7-carboxylic acid esters;

Explanation of the essence of the invention

The diethyldihydropyrazolo (i) -tQthi'azolecarboxylic acid esters of general formula III in which R is an alkyl radical,

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B ^{1 represents} an optionally substituted rienyl radical,

an alkyl radical or an alkoxycarbonyl radical and R ^ is a hydrogen atom or an acetyl group, can be prepared by reacting the 3-amino-2-furoyl-5-thio: xo-Δ ^ -pyrazoline-4-carboxylic acid esters of the general formula I ₁ in the R has the above meaning, with carbonyl compounds of the general formula II, in which R ^ and R ^{2 are} as defined above and X is a halogen atom, can be prepared.

The reactions are carried out in an organic solvent, preferably in alcohols. It is necessary to carry out the reactions either in the presence of bases or of mineral acids. The reactions of the 3-amino-2-furoyl-5-thioxo-A ^ -pyrazoline-1-carboxylic acid esters I with the carbonyl compounds II in the presence of bases can be carried out in absolute alcohols with sodium alcoholate or in aqueous alcohols with sodium hydroxide. The reaction temperatures are around 20 ⁰ C. The reactions are completed after a few hints. Upon cooling, the reaction products III crystallize out.

If the reactions of the compounds I and II are carried out in the presence of mineral acids, heating of the components under reflux is necessary. The compounds III are likewise obtained after cooling the reaction mixtures to 5 ° C. in crystalline form. Purification of the reaction products can be carried out by recrystallization from organic solvents,

Ausführungsbeis piele Ausführunpsbeispiel 1 _{

5-Furoyl-6-imino-3-phenyl-5,6-dihydro-o-pyrazole o, β- 1-thiazole-7-carboxylic acid e-methyl styrene 0.01 mol 3-amino-2-furoyl Methyl 5-thioxo-A ^ -pyrazoline-4-carboxylate is dissolved in a solution of sodium hydroxide in aqueous methanol (prepared from 10 ml of sodium hydroxide solution with a concentration of 1 mol / l and 5 hlL of methanol).

240008 2

To this solution is added while shaking 0.015 Ihenacylbromid. During Umschütteins the crystallization takes place, the precipitate is filtered off, washed with methanol and crystallized from ethanol / Ghloroform.

Yield: 2 ^% of theory, melting point 174-1 75 ° C

O ₁₈ H ₁₃ N ₃ O ₄ S (367.3) Ber. N 11.44

Found N, 11.12 I (KBr): NH 3440, CO 1650 cm ^-1

¹ H-NMR (DLISO-dg): OH ₃ O 3.80 (s), GH, Rienyl protons

7.55 (m), furan-3H 7.20 (d), -4H 6.80 (m), -5H 8.05 (d), NH 13.45.

Example 2

2-Acetyl-5-furoyl-6-imino-3-methyl-5,6-dihydro-pyrazolo-1-yl, 1-kythiazole-7-carboxylic acid ethyl ester 0.01 mol 3-amino-2-furoyl 5-thio2: o- A- pyrazoline-4-carboxylic acid ethyl ester is dissolved in a solution of 0.01 mol of sodium in 20 ml of absolute ethanol. 0.01 mol of chloroacetylacetone is added to this solution with shaking. During the Umschütteins crystallization takes place. It is filtered off, the residue is washed with ethanol and crystallized from dimethylformamide / ethanol, yield: 28% of theory Melting point: 136-138 ⁰ C

IR (KBp): CO 1720, I69O cm " ¹ {

¹ H NMR (CDCl ₃ ): CH ₃ CH ₂ O 1.40 (t), CH ₃ CH ₂ O 4.35 Cq), CH ₃ ,

CH ₃ CO 2.43 (s), 2765 (s), furan-3H 7, OT "(d), -4H 6.55 (m), -5H 7.60 (d), NH 13.6.

Explanatory Note 3

, 5-furoyl-6-rimino-5,6-dihydro-pyrazolo [5,1-b] thiazole-3,7-dicarboxylic acid diethyl ester

0.01 mol of ethyl 3-amino-2-furoyl-5-thioxo- A- pyrazoline-4-carboxylate and 0.01 mol of ethyl bromopyruvate are boiled in 20 ml of ethanol with 2-3 drops of concentrated sulfuric acid under reflux heated,

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The mixture is allowed to stand at 5 ° C., filtered off, the residue is washed with ethanol and recrystallized from ethanol. Yield: 14% d, .aih. Melting point: ⁰ O ₆ S (391.4)

₃ 0H ₂ O 4,37 (q),

(d), GH 7.52

IR '(KBr): NH 3340, 00 1715 cm ^{-1 1} H-MR (ODOl ₃ ): CHoOH ₂ O 1.40 (t), furan-3H 7.05 (d7T-4H 6.56 (m) , -5H (s).

For this purpose! Page formulas

O I

2400 08

BOOO-O O = S

J! I + R ¹ COCHE ² X

O NH

III

I NH J ₁ -HX,

BOOO-O = C S

I i

HH = OH , CR ²

O_o = o

Claims (3)

240008 2 Invention claim 1. A process for the preparation of furoyldihydropyrazolo - [), 1-bjthiazolcarbonsäureestern of the general formula III, in which R is an alkyl radical, R 'is an optionally substituted phenyl radical, an alkyl radical or an alkoxycarbonyl radical and R represents a hydrogen atom or an acyl group, characterized in that 3-amino-2-furoyl-5-thioxo-A-pyrazoline-4-carboxylic acid ester of the general formula I in which K has the above meaning, with carbonyl compounds of general formula II in which R1 and R are as defined above and X is a halogen atom, 2. The method according to item 1, characterized in that the reactions are carried out in the presence of bases. 3 · Method according to item 1, characterized in that the reactions are carried out in the presence of mineral acid.