FI60000C - NOW THEREOF FARING FOR THE FRAMSTATION OF AV 1- (3,4,5-TRIMETOXYCINNAMOYL) PIPERAZINE - Google Patents

Description

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C (45) 11 '11 1 ^ (SI) Kv.ik.3 / Int.ci.3 c 07 D 295/18 FINLAND — FINLAND pi) ^ «ιμ ^ .- ν« μλ «ιι» ι Θ00903 (22 ) Hak «mi * pUv> - AmBknlngtdag 2k.03.80 (23) The beginning of the cloud — Cllti (h« tsd «f 15.06.72 (41) Tullut JulklMksI - Bllvlt off« Nll | 2U. 03.80

Patent and Registration Office ,, ............,. .

'(44) Date of issue. -

Patent and registration authorities AraOktn utlagd och utUkrtftun publicarad 31.07.8l (32) (33) (31) PjrrdSttjr «cuoikMis — Baftrd prloritst (71) Delaiande SA, 32 rue Henri Regnault, Courbevoie (Hauts-de-Seine), France (FR) (72) Gerard Huguet, Le Pinson Malesherbes (Loiret), Claude Fauran, Paris,

Guy Raynaud, Paris, Bernard Pourrias, Meudon la Foret (Hauts-de-Seine),

Michel Turin, Paris, France-France (FR) (7 * 0 Leitzinger Oy (5 * +) New process for the preparation of 1- (3,1 +, 5-trimethoxycinnamoyl) piperazine - Nytt förfarande för framställning av l- (3, ^ , 5-trimethoxy-cinnamoyl) piperazine (62) Separated from application 1712/72 - Avdelad frln trap 1712/72

The present invention relates to a new process for the preparation of 1- (3,4,5-trimethoxycinnamoyl) piperazine of formula I

H3CVa / - \ H3CQ "~ '\ CH = CH— CO— N_NH (i)

H3CO

The compounds of formula I prepared according to the invention are useful in the preparation of pharmaceutically valuable piperazine derivatives of the formula h 3c

H3CO

2,600,000 The preparation of these compounds has been described e.g. in "Chimie Therapeutique", No. 4, pages 290-292 (1969), according to which substituted piperazine is reacted with 3,4,5-trimethoxycinnamoyl acid halide. The starting materials used in such a process are difficult to prepare, so the cost of the compound to be prepared is quite high. Another disadvantage is that cleavage of the reagent chain occurs in the reaction and this cleaved chain is attached to the unsubstituted type atom of the starting piperazine to give a disubstituted piperazine as a by-product.

It has now surprisingly been found that a compound of formula I can be prepared in a simple manner with virtually no undesired by-products by reacting 1- (3,4,5-trimethoxycinnamoyl) -4-nitrosopiperazine with urea in hydrochloric acid solution. The starting materials used in the invention are all readily available commercially. In addition, the process can be completed in a simple manner and the side reactions do not interfere with the course of the reaction.

The following is an example of the application of the method according to the invention.

Example

To a solution of 103 g (0.4 moles) of 3,4,5-trimethoxy-cinnamic acid chloride in 800 mL of chloroform with 51 g (0.6 moles) of sodium bicarbonate is added 46 g (0.4 moles) over 35 minutes. nitroso-piperazine, after which the mixture is allowed to refrigerate for 6 hours. The resulting solution is filtered and the filtrate is concentrated. Thus 120 g of 1- (3,4,5-trimethoxycinnamoyl) -4-nitrosopiperazine are obtained, which is used without further purification. At 80 [deg.] C., a suspension of 33.5 g (0.1 mol) of 1- (3,4,5-trimethoxycinnamoyl) -4-nitrosopiperazine in 330 ml of a 10% aqueous hydrogen chloride solution is stirred for 6 hours. is 6 g (0.1 mol) of urea. The resulting solution is filtered and the filtrate is concentrated. After recrystallization from absolute alcohol, 17 g of 1- (3,4,5-trimethoxycinnamoyl) piperazine chlorohydrate are obtained.

Sp. 192 ° C, 50% yield.