CZ131395A3 - Process for preparing 2-phenyl-1,2-dihydro-1,5-dimethyl-4-£(1/methylethyl)amino|-3h-pyrazol-3-one - Google Patents

Abstract

This invention involves a method of producing 2-phenyl-1,2-dihydro-1,5-dimethyl-4[(1-methylethyl)amino]-3H-pyrazol-3-one of formula I also called Isopyrin from 4-nitrosoantipyrin by a single-stage catalytic hydrogenation with alkylation by acetone which is characterised by the application of a Pt/C catalyst. The catalyst is used repeatedly and the product is obtained through isopyrin hydrochloride monohydrate, obtained from the reaction mixture after filtering the catalyst by acidification with HCl, by releasing by a suitable water base. Isopyrin is a well-known therapeutic drug with antipyretic, analgesic and antirheumatic effects.<IMAGE>

Description

Technical field

The invention relates to a process for the preparation of 2-phenyl-1,2-dihydro-1,5-dimethyl-4- [(1-methylethyl) anino] -3H-pyrazol-3-one, synonymous with 4-isopropylamino-2,3- Dimethyl-1-phenyl-3-pyrazolin-5-one or isopropylaminophenazone, further ramifenazone or isopyrine. It is a drug with antipyretic, analgesic and antirheumatic effects.

BACKGROUND OF THE INVENTION

2-Phenyl-1,2-dihydro-1,5-dimethyl-4- [C1-methylethyl] aminol-3H-pyrazol-3-one of formula I

ie.isopyrin. can be produced in several ways.

In particular, the precursor may be 4-amino-2-phenyl-1,2-dihydro-1,5-dimethyl-3H-pyrazol-3-one synonym of 4-aminoantipyrrine which is an alkyl and alkyl halide <DE 90 959. DE 414 012). eg isopropyl bromide (CCS 226 947) or by condensation with acetone followed by reduction with chemical agents (CS 217 258. R 76 153) and also by catalytic hydrogenation alkylation with acetone (DE 932 677).

4-Aminoantipyrine is prepared primarily by reduction of 2-phenyl-1,2-dihydro-1,5-dimethyl-4-nitro-1H-pyrazol-3-one. synonym 4-n i trosoant i pyr i n. with citric agents <DE 193 632.CS 217 258.

PL. 51 124. DE 33 (470 02) (US 1877 166) or catalytic hydrogenation (DE DE 328)

-2Production is of industrial importance.When one-stage synthesis is based directly on 4-nitrosoantipyrine of formula II

Isopyrine was prepared by catalytic hydrogenation together with alkylation with acetone. An alkylation reduction in the presence of carbonyl compounds was patented in the presence of activators such as piperidine acetate, hydrochloride, organic and anoraic acids.

For example, 321 g of 4-nitrosoantipyrine was treated in the presence of 100 ml of acetone. 50 ml acetic acid. 60 g Pt / BaSO: <containing 15 g Pt? at 60 ° C and 0.35 MPa hydrogen pressure on isopyrine (yield not shown).

The disadvantages of the processes of this patent are, in particular, the high consumption of the expensive catalyst, and thus the high recovery costs of the platinum. Difficult product isolation due to the content of acid activators.

SUMMARY OF THE INVENTION

The present invention is based on a production method

2-phenyl-1,2-dihydro-1,5-dimethyl-4- [C1-methyl-ethyl-amino] -3H-pyrazol-3-one of formula I

AND

-3z 2-Phenyl-1,2-dihydro-1,5-dimethyl-4-nitroso-3H-pyrazol-3-one of Formula II

II by a single-stage catalytic hydrogenation with acetone alkylation characterized in that a Pt / C catalyst without further acidic activators is used in amounts of 1 to 30% by weight per substance II. with a Pt content on the dry matter of 1.0 to 10.0% by weight, with a content of II in acetone of 1.0 to 30.0%, with a water content of acetone of 0 to 10% by weight, at hydrogen pressures of 0.05 MPa to 10 MPa, 10 to 100 ° C.

The catalyst is reused after separation and washing with acetone. After filtering off the catalyst, a product such as hydrochloride monohydrate is obtained directly from the reaction mixture after acidification with HCl. Isopyrine base is obtained from isopyrine hydrochloride monohydrate by release with an aqueous base such as aqueous sodium hydroxide.

In the development of this synthesis, it has been found that the addition of acid activators using a Pt / C catalyst does not improve process speed or selectivity and hence do not improve yields.

Activated carbon catalysts are known to also contain active acidic catalytic centers. In this case, after the initial very rapid reduction of the nitroso group, the condensation and then the final hydrogenation to the isopyrine seem to proceed at a sufficient rate.

Because the reaction takes place only in acetone and no other acids are added as in U.S. Pat. No. 930 328, the process is considerably simplified and cheaper. After filtering off the catalyst and washing it with acetone, it is reused for several

Claims (4)

PATENT CLAIMS A process for the preparation of 2-phenyl-1,2-dihydro-1,5-dimethyl-4- [C1-methylethyl) amino] -3H-pyrazol-3-one of formula I from 2-phenyl-1,2- of dihydro-1,5-dimethyl-4-nitroso-3H-pyrazol-3-one of formula II by one-step catalytic hydrogenation with acetone alkylation. The use of a Pt / C catalyst without further acidic activators is used in an amount of 1 to 30% by weight. to substance II, with a Pt content on the catalyst dry mass of 1.0 to 10.0¾ wt., with a content of II in acetone of 1.0 to 30¾ with a water content in acetone of 0 to 10¾ wt. MPa at -10 to 100 ° C. 2. The process of claim 1 wherein the catalyst is reused after separation and washing. 3. The process according to claim 1 or 2, characterized in that after filtering off the catalyst, a product such as the hydrochloride monohydrate is obtained directly from the reaction mixture. after acidification with HCl. 4. A process according to any one of claims 1 to 3 wherein the isopyrine base is obtained from isopyrine hydrochloride monohydrate by release with an aqueous base such as aqueous sodium hydroxide.