CS261444B1

CS261444B1 - New 1-methyl-5-/1-propylamino/-6-aminouracil and method of its preparation

Info

Publication number: CS261444B1
Application number: CS875636A
Authority: CS
Inventors: Ladislav Ing Csc Stibranyi; Miroslav Ing Csc Veverka
Original assignee: Stibranyi Ladislav; Veverka Miroslav
Priority date: 1987-07-28
Filing date: 1987-07-28
Publication date: 1989-02-10
Also published as: CS563687A1

Abstract

Riešenie sa týká nového l-metyl-5-(l-propylamíno)-6-amínouracilu a spósobu jeho přípravy. Předmětná zlúčenina sa připravuje amonolýzou l-metyl-5-bróm-6-amínouracilu 1-propylamínom, vodným roztokom propylamínu alebo roztokom propylamínu v alkohole Ci až Ci pri teplotách 40 až 140 °C. l-metyl-5-(1-propylamíno)-6-amínouracil je dóležitým medziproduktom pre přípravu farmakologicky dóležitého 3-metyl-7-propylxantínu.The present invention relates to a novel 1-methyl-5- (1-propylamino) -6-aminouracil and his way of preparation. The subject compound is prepared amonolysis of 1-methyl-5-bromo-6-aminouracil With 1-propylamine, an aqueous solution of propylamine or a solution of propylamine in an alcohol C 1 to C 1 at temperatures of 40 to 140 ° C. l-methyl-5- (1-propylamino) -6-aminouracil is an important intermediate for preparation pharmacologically important 3-methyl-7-propylxanthine.

Description

Predmetom vynálezu je nový l-metyl-5-(1-propylamíno j-6-amínouracil vzorca IThe present invention relates to a novel 1-methyl-5- (1-propylamino) -6-aminouracil of the formula I

C^/NHCH₂CH^CH₃ ^NH2CH _{2 /} CH ₂ CH 2 CH ₃ ^NH 2

C.H, (I) a sposob jeho přípravy. Uvedená zlúčenina je medziproduktom pre přípravu farmakologicky účinných purínových báz.C.H, (I) and method of its preparation. Said compound is an intermediate for the preparation of pharmacologically active purine bases.

Je známy 5-metylanalóg predmetnej zlúčeniny vzorca I, ktorý sa připravuje reakciou l-metyl-5-bróm-6-amínouracilu s metylamínom (Wojciechowski, polský patent 42 976 Acta Polon. Pharm. 18 409—13 1961) a ktorý slúžia ako medziprodukt na přípravu teobromínu. Předmětná zlúčenina vzorca I umoižňuje selektívnu syntézu 3-metyl-7-propylxantínu.The 5-methylanolog of the present compound of formula I is known which is prepared by reacting 1-methyl-5-bromo-6-aminouracil with methylamine (Wojciechowski, Polish patent 42 976 Acta Polon. Pharm. 18 409-13 1961) and which serves as an intermediate for preparing theobromine. The present compound of formula I allows the selective synthesis of 3-methyl-7-propylxanthine.

Zlúčenina vzorca I sa připravuje z 1-metyl-5-bróm-6-amínouracilu vzorca IIThe compound of formula I is prepared from 1-methyl-5-bromo-6-aminouracil of formula II

OABOUT

reakciou s propylamínom. V důsledku nízkej teploty varu propylamínu sa reakcia uskutočňuje v uzavretom miešanom autokláve. Pri amonolýze je možno použiť aj vodný roztok 1-propylamínu alebo možno pracovat’ s roztokom propylamínu v alkohole Ci až Cd, v ktorom sú jednotlivé zložky lepšie rozpustné. Teplota pri amonolýze brómderivátu vzorca II sa udržiava v rozmedzí 40 až 140 stupňov C a molárny poměr 1-propylamínu k brómderivátu vzorce II je 2 : 1 až 20 : 1, pričom sa přebytečný propylamín po skončení reakcie regeneruje destiláciou.. Struk4 túra predmetnej zlúčeniny vzorca I bola potvrdená ’-Η NMR, ¹³C NMR a analýzou C, Η, N.by reaction with propylamine. Due to the low boiling point of propylamine, the reaction is carried out in a closed stirred autoclave. For ammonolysis, an aqueous solution of 1-propylamine can also be used, or a solution of propylamine in a C1-Cd alcohol can be used, in which the individual components are more soluble. The ammonolysis temperature of the bromo derivative of formula II is maintained at 40 to 140 degrees C and the molar ratio of 1-propylamine to bromo derivative of formula II is 2: 1 to 20: 1, the excess propylamine being recovered by distillation after completion of the reaction. I was confirmed by 1 H-NMR, ¹³ C NMR and analysis of C,,, N.

V ďalšom je predmet vynálezu objasněný na príkladoch bez toho, že by sa na tieto výlučné obmedzoval.In the following, the invention is illustrated by way of example without being limited thereto.

Přikladl l-metyl-5- (1-propylamíno) -6-amínouracil g (0,045 M) l-metyl-5-bróm-6-amínouracilu sa suspenduje v 50 ml vody a k suspenzii sa za miešania přidá 14,5 g (20 ml, 0,24 M) 1-propylamínu tak, aby teplota nepřekročila 50 °C. Po podaní propylamínu sa zmes zahrieva v uzavretej tlakovej trubici 1 h na teplotu 140 °C, po skončení reakcie sa roztok přefiltruje a z filtrátu po ochladení v.ypadnú žité ihličky l-metyl-5-(1-propylamíno )-6-amínouracilu (5,5 g, 61 °/o) s t. t. 217—225 °C.EXAMPLE 1 1-Methyl-5- (1-propylamino) -6-aminouracil g (0.045 M) of 1-methyl-5-bromo-6-aminouracil was suspended in 50 ml of water and 14.5 g (20 ml) was added under stirring. ml, 0.24 M) of 1-propylamine such that the temperature does not exceed 50 ° C. After the administration of propylamine, the mixture was heated in a sealed pressure tube at 140 ° C for 1 hour, after completion of the reaction, the solution was filtered and, after cooling, the sparse rye needles of 1-methyl-5- (1-propylamino) -6-aminouracil (5) were filtered. 5 g, 61% (m) with m.p. t. Mp 217-225 ° C.

N vypočítané 28,26 °/o, N nájdené 27,82 °/o. Příklad 2 l-metyl-5- (1-propylamíno) -6-amínouracil g (0,0227 M) l-metyl-5-bróm-6-amínouracilu sa v uzavretej sklenenej tlakovej nádobě mieša s 29 g (40 ml, 0,49 Mj 1-propylamínu pri teplote 60 ^PC 6 h, na druhý deň sa prebytočný 1-propylamín oddestiluje a destilačný zvyšok sa supenduje v 40 ml metanolu. Vypadnutá kryštalická látka sa premyje malým množstvom studenej vody. Získá sa 4 g surového l-metyl-5-(1-propylamíno)-6-amínouracilu (89,1 ^u/oj s t. t. 218 až 225 °C.N calculated 28.26 ° / o, N found 27.82 ° / o. EXAMPLE 2 1-Methyl-5- (1-propylamino) -6-aminouracil g (0.0227 M) of 1-methyl-5-bromo-6-aminouracil is mixed with 29 g (40 ml, 0 ml) in a sealed glass pressure vessel. , 49 ms 1-propylamine at 60 C for 6 h ^L, the following day, the excess 1-propyl amine was distilled off and the distillation residue was then suspended in 40 ml of methanol. the precipitated crystal was washed with a little cold water. 4 g of crude l- methyl-5- (1-propylamino) -6-aminouracil (89.1 ^u / os with mp 218-225 ° C.

Příklad 3 l-metyl-5-(1-propylamíno)-6-amínouracil g (0,0227 Mj l-metyl-5-bróm-6-amínouracilu sa přidá k 150 ml metanolu a k tejto zmesi sa opatrné za chladenia a miešania přidá 5 g (7 ml, 0,084 M) 1-propylamínu. Reakčná zmes sa mieša pri teplote 80 °C 8 h, po skončení reakcie sa oddestiluje polovica metanolu a po· ochladení sa odsáté kryštaliky prekryštalizujú z minima vody. Získá sa 2,5 g (55,6 %) l-metyl-5-(1-propylamíno)-6-amínouracilu s t. t. 220 až 225 stupňov Celsia.EXAMPLE 3 1-Methyl-5- (1-propylamino) -6-aminouracil g (0.0227 IU of 1-methyl-5-bromo-6-aminouracil) was added to 150 ml of methanol and added cautiously with cooling and stirring to this mixture. 5 g (7 ml, 0.084 M) of 1-propylamine The reaction mixture was stirred at 80 ° C for 8 h, after completion of the reaction, half of methanol was distilled off and after cooling, the aspirated crystals were recrystallized from a minimum of water to give 2.5 g. (55.6%) of 1-methyl-5- (1-propylamino) -6-aminouracil of mp 220-225 degrees Celsius.

Claims

1. New 1-methyl-5- (1-propylamino) -6-aminouracil of formula (II):

II 'C ^ NH CH ₀ CH ₃ CH ₃

N

I

CH

NH "fl)

2. A process for the preparation of a compound according to claim 1, characterized in that 1-methyl-5-bromo-6-aminouracil of the formula II {

Br) is reacted with 1-propylamine. ¹

3. The process according to claim 2, wherein the ammonolysis of the bromo derivative of the formula II is carried out with anhydrous propylamine, an aqueous solution of propylamine, or a solution of propylamine in an aliphatic alcohol Ct to Cd.